Biocompatible dialysis fluids for peritoneal dialysis

  • Review
  • Intervention

Authors

  • Yeoungjee Cho,

    Corresponding author
    1. Princess Alexandra Hospital, Department of Nephrology, Woolloongabba, Queensland, Australia
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  • David W Johnson,

    1. Princess Alexandra Hospital, Department of Nephrology, Woolloongabba, Queensland, Australia
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  • Jonathan C Craig,

    1. The University of Sydney, Sydney School of Public Health, Sydney, NSW, Australia
    2. The Children's Hospital at Westmead, Cochrane Kidney and Transplant, Centre for Kidney Research, Westmead, NSW, Australia
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  • Giovanni FM Strippoli,

    1. The Children's Hospital at Westmead, Cochrane Kidney and Transplant, Centre for Kidney Research, Westmead, NSW, Australia
    2. University of Bari, Department of Emergency and Organ Transplantation, Bari, Italy
    3. Diaverum, Medical Scientific Office, Lund, Sweden
    4. Diaverum Academy, Bari, Italy
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  • Sunil V Badve,

    1. Princess Alexandra Hospital, Department of Nephrology, Woolloongabba, Queensland, Australia
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  • Kathryn J Wiggins

    1. Royal Melbourne Hospital, Departments of Nephrology and General Medicine, Melbourne, VIC, Australia
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Abstract

Background

The longevity of peritoneal dialysis (PD) is limited by high rates of technique failure, some of which stem from peritoneal membrane injury. 'Biocompatible' PD solutions have been developed to reduce damage to the peritoneal membrane.

Objectives

This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD.

Search methods

We searched the Cochrane Renal Group's Specialised Register (28 February 2013), through contact with the Trials Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE, and handsearching conference proceedings.

Selection criteria

All randomised controlled trials (RCTs) and quasi-RCTs in adults and children comparing the effects of biocompatible PD solutions (neutral pH, lactate-buffered, low glucose degradation product (GDP); neutral pH, bicarbonate (± lactate)-buffered, low GDP; glucose polymer (icodextrin)) in PD were included. Studies of amino acid-based PD solutions were excluded.

Data collection and analysis

Two authors extracted data on study quality and outcomes (including adverse effects). The authors contacted investigators to obtain missing information. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for categorical variables, and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous variables.

Main results

Thirty-six eligible studies (2719 patients) were identified: Neutral pH, lactate-buffered/bicarbonate (± lactate)-buffered, low GDP PD solution (24); icodextrin (12). Allocation methods and concealment were generally incompletely reported, and adequate in only ten studies (27.8%). Patients lost to follow-up ranged from 0% to 83.4%.

Neutral pH, low GDP versus conventional glucose PD solution

Based on generally sub-optimal quality evidence, the use of neutral pH, low GDP PD solutions was associated with larger urine volumes at the end of the studies, up to three years of therapy duration (7 studies, 520 patients: MD 126.39 mL/d, 95% CI 26.73 to 226.05). Improved preservation of residual renal function was evident in studies with greater than 12 month follow-up (6 studies, 360 patients: SMD 0.31, 95% CI 0.10 to 0.52). There was no significant effect on peritonitis, technique failure or adverse events with the use of neutral pH, low GDP PD solutions.

Glucose polymer (icodextrin) versus conventional glucose PD solution

There was a significant reduction in episodes of uncontrolled fluid overload (2 studies, 100 patients: RR 0.30, 95% CI 0.15 to 0.59) and improvement in peritoneal ultrafiltration (4 studies, 102 patients, MD 448.54 mL/d, 95% CI 289.28 to 607.80) without compromising residual renal function (4 studies, 114 patients: SMD 0.12, 95% CI -0.26 to 0.49) or urine output (3 studies, 69 patients: MD -88.88 mL/d, 95% CI -356.88 to 179.12) with icodextrin use. A comparable incidence of adverse events with the icodextrin (four studies) was reported.

Authors' conclusions

Based on generally sub-optimal quality studies, use of neutral pH, low GDP PD solution led to greater urine output and higher residual renal function after use exceeded 12 months. Icodextrin prescription improved peritoneal ultrafiltration and mitigated uncontrolled fluid overload. There were no significant effects on peritonitis, technique survival, patient survival or harms identified with their use. Based on the best available evidence, the use of these 'biocompatible' PD solutions resulted in clinically relevant benefits without added risks of harm.

摘要

腹膜透析用的生物相容性透析液

背景

腹膜透析 (peritoneal dialysis, PD) 的壽命,因技術性失敗率偏高而受到限制,部分原因來自於腹膜損傷。目前已研發出「生物相容性」(Biocompatible) 腹膜透析液,可降低對腹膜的傷害。

目的

本次文獻回顧旨在瞭解相對於標準腹膜透析液生物相容性腹膜透析液對接受腹膜透析患者的效益和傷害。

搜尋策略

我們與試驗搜尋協調員聯絡,利用與此次文獻回顧相關的字彙,搜尋考科藍腎臟群組專業註冊 (Cochrane Renal Group's Specialised Register) (2013年2月28日),並採取專為CENTRAL、MEDLINE和EMBASE設計的搜尋策略,找尋專業註冊中的試驗。此外,我們也以人工搜尋的方式,尋找研討會的會議記錄。

選擇標準

此次文獻回顧的納入條件為所有隨機對照試驗 (randomized controlled trial, RCT) 和半隨機對照試驗 (quasi-RCT),試驗對象為成人與兒童,研究主題為比較生物相容性腹膜透析液 (酸鹼值中性、乳酸鹽緩衝、低葡萄糖代謝產物 [glucose degradation product, GDP];酸鹼值中性、重碳酸鹽 [±乳酸鹽] 緩衝、低GDP;葡萄糖聚合物 [icodextrin]) 的效果。我們排除採用含氨基酸腹膜透析液的試驗。

資料收集與分析

由2位作者負責萃取關於試驗品質和結果 (包含不良作用) 的資料。本文獻回顧的作者也聯絡試驗主持人,以收集遺漏的資訊。本次文獻回顧採用隨機效果模式 (random-effects model)來獲得試驗結果的摘要估計值,並以風險比 (risk ratio, RR) 和95%信賴區間 (confidence interval, CI)來呈現結果;以平均差 (mean difference, MD) 或標準化平均差 (standardised mean difference, SMD)以及95% CI計算連續變項。

主要結果

有36篇試驗符合本次文獻回顧的納入條件 (包含2719名患者):包括酸鹼值中性、乳酸鹽緩衝 / 重碳酸鹽 [±乳酸鹽] 緩衝、低GDP的腹膜透析液 (24篇);icodextrin (12篇)。這些試驗通常並未完整報告分組方法和隱匿方式 (concealment),而且只有10篇試驗採取適當程序 (27.8%)。未能接受追蹤的患者約佔0%至83.4%。

酸鹼值中性、低GPD透析液相對於傳統葡萄糖腹膜透析液

根據品質普遍不夠理想的證據,使用酸鹼值中性、低GPD的腹膜透析液,可能與試驗結束時的排尿量較多有關,治療持續時間長達3年 (7篇試驗,520名患者:MD為126.39 mL/d,95% CI為26.73至226.05)。追蹤超過12個月的試驗證實,可保留更多殘餘腎功能 (6篇試驗,360名患者:SMD為0.31,95% CI為0.10至0.52)。使用酸鹼值中性的低GDP腹膜透析液,對腹膜炎、技術性失敗或不良事件並無顯著影響。

葡萄糖聚合物 (icodextrin) 相對於傳統葡萄糖腹膜透析液

使用icodextrin可顯著降低控制不良的體液容積過量 (fluid overload) (2篇試驗,100名患者:RR為0.30,95% CI為0.15至0.59)、改善腹膜透析的超過濾作用 (ultrafiltration) (4篇試驗,102名患者:MD為448.54 mL/d,95% CI為289.28至607.80),且不會損及殘餘腎功能 (residual renal function) (4篇試驗,114名患者:SMD為0.12,95% CI為-0.26至0.49) 或排尿量 (3篇試驗,69名患者:MD為-88.88 mL/d,95% CI為-356.88至179.12)。不良事件發生率和icodextrin相似 (4篇試驗)。

作者結論

根據品質普遍不夠理想的試驗,使用酸鹼值中性的低GDP腹膜透析液超過12個月,可使患者的排尿量增加,也能保留較多的殘餘腎功能。使用icodextrin可改善腹膜透析的超過濾作用,並減輕控制不良的體液容積過量。對腹膜透析所引起的腹膜炎、技術有效期間 (technique survival)、患者存活期或對患者的傷害,並無顯著影響。依據現有的最佳證據,使用這些「生物相容性」腹膜透析液具有臨床相關效益,而且不會增加傷害風險。

譯註


翻譯者:臺北醫學大學實證醫學研究中心
本翻譯計畫由衛生福利部補助經費,臺北醫學大學實證醫學研究中心、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行。

Plain language summary

Biocompatible dialysis fluids for peritoneal dialysis

Peritoneal dialysis (PD) is a form of treatment for people with advanced kidney disease to an extent where their own kidney function is inadequate to meet the body's requirements. PD is flexible, and allows for therapy to be instituted by patients at home. After initial surgical insertion of a catheter into the abdomen, patients are required to perform regular exchange of PD solution at a prescribed rate to allow clearance of toxins and fluids across the peritoneal membrane. Unfortunately, the longevity of PD is limited, which is largely due to peritoneal membrane injury that results from the use of biologically 'unfriendly' PD solutions. The 'unfriendly' characteristics of these solutions include high glucose levels, glucose breakdown products and acidity. To overcome these hurdles, biocompatible PD solutions (i.e. neutral pH, lowered levels of glucose breakdown products, use of materials alternative to glucose such as icodextrin) have been manufactured that are designed to cause less damage to the peritoneal membrane. This review of interventions testing the benefits and harms of biocompatible PD solutions identified 36 studies (2719 patients).

When compared to conventional PD solutions, we found that neutral pH, low glucose breakdown product PD solution resulted in better preservation of patient's own kidney function including urine output (7 studies, 520 patients), with on average 126.39 mL greater urine output per day. Patients who received glucose polymer (icodextrin) PD solutions were 70% less likely to experience uncontrolled episodes of fluid overload (2 studies, 100 patients).

No significant harms with their use were reported by 10 studies. Many of the studies were of small size, short follow-up duration, poor quality, and had inconsistent reporting of outcomes. Further studies within this area are needed.

淺顯易懂的口語結論

腹膜透析用的生物相容性透析液

腹膜透析為晚期腎臟疾病患者的一種治療,這些患者的腎臟功能已經不足以應付身體需求。腹膜透析相當具有彈性,患者可在家中進行治療。剛開始時醫師需要以外科手術,將1條導管埋入患者的腹腔,手術後患者必須定期按醫師處方的速率進行腹膜透析液交換,以便透過腹膜清除體內的毒素和液體。遺憾的是,腹膜透析的使用壽命有限,主要導因於使用對身體「不利」的腹膜透析液所造成的傷害。透析液對身體「不利」的特性包括高葡萄糖濃度、葡萄糖分解產物和酸性。為了克服這些障礙,人們已製造出生物相容性腹膜透析液 (即酸鹼值中性、葡萄糖分解產物濃度偏低,以其他物質取代葡萄糖,例如icodextrin),試圖降低對腹膜的損傷。本篇針對介入法的文獻回顧,納入36篇試驗 (2719名患者),旨在檢視生物相容性腹膜透析液的效益和傷害。

我們發現,相較於傳統的腹膜透析液,酸鹼值中性且葡萄糖分解產物濃度偏低的腹膜透析液,有助於保留患者自身的腎功能,包括排尿量 (7篇試驗,520名患者),患者每天的排尿量平均增加126.39 mL。使用葡萄糖聚合物 (icodextrin) 腹膜透析液,可使患者的控制不良體液容積過量發生率降低70% (2篇試驗,100名患者)。

有10篇試驗指出,使用生物相容性腹膜透析液不會造成顯著傷害。上述許多試驗樣本數少、追蹤期短、品質不良,而且所得出的結果也不一致。這個領域還需要進行進一步的試驗。

譯註


翻譯者:臺北醫學大學實證醫學研究中心
本翻譯計畫由衛生福利部補助經費,臺北醫學大學實證醫學研究中心、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行。

Laienverständliche Zusammenfassung

Biokompatible Dialyselösungen für Peritonealdialyse (Bauchfelldialyse)

Peritonealdialyse (PD) ist eine Behandlung für Patienten mit fortgeschrittener Nierenerkrankung, deren eigene Nieren nicht mehr in der Lage sind alle Funktionen zu erfüllen. PD ist flexibel und ermöglicht eine Behandlung durch den Patienten zu Hause. Nach einmaliger chirurgischer Einführung eines Katheters in die Bauchhöhle, müssen die Patienten den regelmäßigen Austausch von PD-Lösung in vorgegebenen Abständen durchführen, um eine Reinigung von Giftstoffen und Flüssigkeiten durch das Bauchfell zu ermöglichen. Unglücklicherweise ist die Durchführbarkeit einer PD zeitlich begrenzt, was vor allem auf Verletzungen des Bauchfells zurückzuführen ist, die durch die Verwendung von biologisch "unfreundlichen" PD-Lösungen verursacht werden. Die "unfreundlichen" Merkmale dieser Lösungen sind hohe Glukosewerte, Glukoseabbauprodukte und Säure. Um diese Schwierigkeiten zu umgehen, werden biokompatible PD-Lösungen hergestellt, die weniger Schaden am Bauchfell verursachen. Diese sind beispielsweise pH-neutral, enthalten niedrige Mengen von Glukoseabbauprodukten, oder verwenden alternative Materialien zu Glukose wie Icodextrin. Diese Übersichtsarbeit, die den Nutzen und Schaden von biokompatiblen PD-Lösungen untersucht, schließt 36 Studien mit 2719 Patienten ein.

Im Vergleich zu herkömmlichen PD-Lösungen zeigte sich bei pH-neutralen PD-Lösungen mit wenigen Glucoseabbauprodukten eine bessere Erhaltung der verbleibenden Nierenfunktion einschließlich der Harnausscheidung, mit durchschnittlich 126,39 mL höherer Urinausscheidung pro Tag (7 Studien, 520 Patienten). Patienten, die Glukosepolymer (Icodextrin) PD-Lösungen erhielten, hatten eine um 70% verringerte Wahrscheinlichkeit, unkontrollierte Episoden von Überwässerung zu erleiden (2 Studien, 100 Patienten).

Keine signifikanten Schäden im Zusammenhang mit der Verwendung biokompatibler PD-Lösungen wurden in 10 Studien berichtet. Viele der Studien waren von geringer Größe, schlechter Qualität, hatten eine kurze Nachbeobachtungszeit und waren widersprüchlich in der Berichterstattung der Ergebnisse. Weitere Studien in diesem Bereich sind erforderlich.

Anmerkungen zur Übersetzung

I. Töws, Koordination durch Cochrane Schweiz.

Summary of findings(Explanation)

Summary of findings for the main comparison. 
  1. CrCl - creatinine clearance; GFR - glomerular filtration rate; UF - ultrafiltration

Neutral pH, low GDP PD solution versus standard glucose peritoneal dialysis (PD) solution

Patient or population: patients with end-stage kidney disease receiving peritoneal dialysis

Settings: community

Intervention: neutral pH, low GDP PD solution

Comparison: standard glucose PD solution

OutcomesRelative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

RRF

(renal CrCl, GFR; follow-up 3 months to more than 3 years)

SMD 0.16 (-0.01 to 0.32)564
(11)
⊕⊕⊕⊝
moderate
Benefit reached significance once follow-up duration exceeded 12 months.

Urine volume (mL/d)

(follow-up to more than 3 years)

MD 126.39 (26.73 to 226.05)520
(7)
⊕⊕⊕⊕
high
Benefit was greater with longer follow-up duration (i.e. longer than 12 months)

Peritoneal ultrafiltration - 4 hours (mL/4 hours)

(follow-up to 24 months)

SMD -0.28 (-0.67 to 0.10)196
(6)
⊕⊕⊕⊝
moderate
 

24-hour peritoneal UF (mL/d; mL/d/m²)

(follow-up to more than 3 years)

SMD -0.23 (-0.62 to 0.16)451
(7)
⊕⊝⊝⊝
very low
Unclear disclosure on use of 7.5% icodextrin between groups and prescribed glucose load created challenge for accurate analysis of outcome.

Inflow pain

(follow-up to 6 months)

RR 0.51 (0.24 to 1.08)58
(1)
⊕⊕⊕⊝
moderate
 

Peritonitis rate (episodes/total patient-months)

(up to 24 months)

RR 1.13 (0.77 to 1.66)13802 months
(6)
⊕⊕⊝⊝
low
High risk of attrition bias amongst studies analysed.

Technique failure (death-censored)

(up to more than 3 years)

RR 1.04 (0.60 to 1.78)968
(12)
⊕⊝⊝⊝
very low
None of the studies were adequately powered. Number after combining studies remained too small to accurately assess this outcome.
CI: Confidence interval; RR: Risk Ratio; SMD: Standardised mean difference
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Summary of findings 2

Summary of findings 2. 
  1. CrCl - creatinine clearance; GFR - glomerular filtration rate

Glucose polymer (icodextrin) versus standard glucose peritoneal dialysis (PD) solution

Patient or population: patients with end-stage kidney disease receiving peritoneal dialysis

Settings: community

Intervention: glucose polymer (icodextrin) PD solution

Comparison: standard glucose PD solution

OutcomesRelative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Uncontrolled fluid overload

(follow-up to 24 months)

RR 0.30 (0.15 to 0.59)100
(2)
⊕⊕⊕⊝
moderate
 

Rash

(follow-up to 12 months)

RR 2.51 (0.59 to 10.72)755
(3)
⊕⊕⊕⊝
moderate
 

RRF (GFR; renal CrCl)

(follow-up to 24 months)

SMD 0.12 (-0.26 to 0.49)114
(4)
⊕⊕⊕⊝
moderate
 

Urine volume (mL/d)

(follow-up to 24 months)

MD -88.88 (-356.88 to 179.12)69
(3)
⊕⊕⊕⊝
moderate
Limited number of long-term studies

Daily ultrafiltration (mL/d)

(follow-up to 24 months)

MD 448.54 (289.28 to 607.80)102
(4)
⊕⊕⊕⊕
high
 

Peritoneal CrCl

(follow-up to 12 months)

SMD 0.36 (-0.24 to 0.96)237
(3)
⊕⊕⊕⊝
moderate
Studies where analysis was categorised per membrane transport characteristics showed significant benefit in favour of icodextrin in those with greater than low membrane transport characteristics

Technique survival (death censored)

(up to 24 months)

RR 0.58 (0.28 to 1.20)290
(3)
⊕⊝⊝⊝
very low
 
CI: Confidence interval; RR: Risk Ratio; SMD: Standardised mean difference
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Background

Description of the condition

Peritoneal dialysis (PD) is a widely utilised method of renal replacement therapy, and in some populations is the modality used by more than half of all patients receiving dialysis (Cueto-Manzano 2007). In some patient groups the longevity of PD is limited. For example, in Australia and New Zealand, the estimated median duration of PD treatment is 2.5 years (Brown 2011). Psychosocial factors and catheter problems contribute to early technique failure, and kidney transplantation accounts for cessation of PD in some patients. Causes of later technique failure include ultrafiltration (UF) failure, PD-associated peritonitis and inadequate solute clearance (Brown 2011).

Increased duration of PD is associated with development of morphological changes in the peritoneal membrane. Changes that occur include thickening of the submesothelial compact collagenous zone and subendothelial hyalinisation of postcapillary venules, with obliteration or narrowing of the vascular lumen (Williams 2003). The risk of encapsulating sclerosing peritonitis increases with longer duration of PD (Johnson 2010; Rigby 1998). Progressive damage to the peritoneal membrane contributes to inadequate solute clearance, UF failure and change in peritoneal membrane transport properties, hence inability of the membrane to function adequately. Loss of residual renal function (RRF) contributes to both UF failure and reduced solute clearance and is a predictor of increased mortality (Bargman 2001).

Conventional PD solutions rely on hyperosmolar dextrose solutions to achieve an adequate gradient for UF across the peritoneal membrane, and addition of lactate as a buffer (Palmer 2004). Heat sterilisation of solutions results in generation of glucose degradation products (GDP) (Nilsson-Thorell 1993; Wieslander 1996). Consequently, conventional PD solutions are hyperosmolar, acidic and have a high lactate concentration, and have been implicated in the development of damage to the peritoneal membrane. They may also impair host defences (Jorres 1992; Topley 1997). Proposed methods by which these adverse effects occur include generation of advanced glycation end products (AGE) (Lamb 1995; Nakayama 1997), promotion of fibrosis (Pollock 2005), neovascularization (Mateijsen 1999) and impairment of peritoneal macrophage function (Mortier 2004a).

Description of the intervention

Newer, biocompatible, dialysis solutions have been designed to minimise perturbation of the physiological milieu in the peritoneal cavity. The main approaches to creation of biocompatible solutions have been generation of solutions with a neutral pH and low GDP content, use of bicarbonate (± lactate) buffer, substitution of dextrose with glucose polymers, and use of amino acids as the osmotic agent. 

How the intervention might work

Results of in vitro studies and small studies using surrogate end points suggest that biocompatible PD fluids may cause less damage to the peritoneal membrane than conventional fluids, and hence may improve patient outcomes (Mortier 2004b; Mortier 2005). Improvement in peritoneal morphology with use of biocompatible PD solution has also been reported (Ayuzawa 2012). Furthermore, use of glucose polymer PD solution has been shown to augment peritoneal UF (Johnson 2003).

Why it is important to do this review

In comparison to conventional PD solutions, these biocompatible solutions are more costly, and the effect of these solutions on 'hard' (patient-level clinical outcomes) endpoints is unclear. Furthermore, their role in clinical practice has not been established.

Objectives

This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD.

Methods

Criteria for considering studies for this review

Types of studies

All randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at the effects of biocompatible dialysis solutions on patient outcomes in PD. The first period of randomised cross-over studies was also included. When it was not possible to establish which data from cross-over studies was from the first arm of the study, studies were excluded from the meta-analysis.

Types of participants

Inclusion criteria

Adults and children who were receiving any type of home based PD (continuous ambulatory PD (CAPD) or automated PD (APD)).

Exclusion criteria

Studies of amino acid based dialysis fluids were not included.

Types of interventions

Studies comparing the treatment of biocompatible PD solution to conventional PD solution were included. Groups of biocompatible PD solutions considered were:

  • Neutral pH, lactate-buffered, low GDP

  • Neutral pH, bicarbonate (± lactate)-buffered low GDP

  • Glucose polymer (icodextrin)

  • Combination regimens (e.g. PPEN)

The following types of studies were included:

  • Studies of neutral pH, low GDP PD solutions (lactate and bicarbonate ± lactate buffered) against conventional PD solutions

  • Studies of icodextrin against conventional PD solution

Types of outcome measures

Primary outcomes
  • Decline in RRF (changes in residual creatinine clearance (CrCl), urea clearance, Kt/V, glomerular filtration rate (GFR) and urine output)

  • Peritoneal UF (during peritoneal equilibration test and daily UF)

  • Peritonitis rate (episodes/y, episode/total patient-months on PD) and incidence (number of events/follow-up period)

  • Technique survival (number of patients remaining on PD at study completion)

  • Patient survival (number of patients alive at study completion)

  • Toxicity/adverse events (e.g. rash, uncontrolled fluid overload)

Secondary outcomes
  • Inflow pain

  • Changes in peritoneal membrane transport (four-hour dialysate:plasma creatinine)

  • Dialysis adequacy (CrCl, Kt/V)

  • Hospitalisation (number of hospitalisation days during study follow-up period)

Search methods for identification of studies

Electronic searches

We searched the Cochrane Renal Group's Specialised Register on 28 February 2013 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. The Cochrane Renal Group’s Specialised Register contains studies identified from the following sources.

  1. Monthly searches of the Cochrane Central Register of Controlled Trials CENTRAL

  2. Weekly searches of MEDLINE OVID SP

  3. Handsearching of renal-related journals & the proceedings of major renal conferences

  4. Searching of the current year of EMBASE OVID SP

  5. Weekly current awareness alerts for selected renal-journals

  6. Searches of the International Clinical Trials Register (ICTRP) Search Portal & ClinicalTrials.gov

Studies contained in the Specialised Register are identified through search strategies for CENTRAL, MEDLINE, and EMBASE based on the scope of the Cochrane Renal Group. Details of these strategies as well as a list of handsearched journals, conference proceedings and current awareness alerts are available in the 'Specialised Register' section of information about the Cochrane Renal Group.

See Appendix 1 for search terms used in strategies for this review.

Searching other resources

  1. Reference lists of nephrology textbooks, review articles and relevant studies.

  2. Letters seeking information about unpublished or incomplete studies to investigators known to be involved in previous studies.

Data collection and analysis

Selection of studies

The review was undertaken by six authors. The search strategy described was used to obtain titles and abstracts of studies that have been relevant to the review. The titles and abstracts were screened independently by two authors. Studies that were not applicable were discarded. Two authors independently assessed retrieved abstracts and, if necessary the full text, of these studies to determine which studies satisfied the inclusion criteria.

Data extraction and management

Data extraction was carried out independently by the same authors using standard data extraction forms. Studies reported in non-English language journals were translated before assessment. Where more than one publication of one study existed, reports were grouped together and the most recent or most complete data set were used. Any discrepancy between published versions was highlighted. Disagreements were resolved by consultation.

Assessment of risk of bias in included studies

The following items were independently assessed by two authors using the risk of bias assessment tool (Higgins 2011) (see Appendix 2).

  • Was there adequate sequence generation (selection bias)?

  • Was allocation adequately concealed (selection bias)?

  • Was knowledge of the allocated interventions adequately prevented during the study (detection bias)?

    • Participants and personnel

    • Outcome assessors

  • Were incomplete outcome data adequately addressed (attrition bias)?

  • Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?

  • Was the study apparently free of other problems that could put it at a risk of bias?

If a sufficient number of studies (greater than 10) measured the same outcome, thereby assessed to have enough power to detect asymmetry, a funnel plot was performed to evaluate for possible publication bias.

Measures of treatment effect

For dichotomous outcomes (e.g. death, inflow pain, peritonitis) results were expressed as risk ratios (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment (e.g. decline in RRF, urine volume), the mean difference (MD) was used, or the standardised mean difference (SMD) if different scales were used. When data were not presented in a format suitable for inclusion in meta-analysis (e.g. median, interquartile range (IQR)), they were presented in tabulated form.

Dealing with missing data

Any further information required from the original author was requested by written correspondence and any relevant information obtained in this manner was included in the review.

Assessment of heterogeneity

Heterogeneity was analysed using a Chi² test on N-1 degrees of freedom, with an alpha of 0.05 used for statistical significance and with the I² test (Higgins 2003). I² values of 25%, 50% and 75% correspond to low, medium and high levels of heterogeneity.

Assessment of reporting biases

Two authors independently assessed the risk of reporting biases in studies using the risk of bias assessment tool (Higgins 2011).

Data synthesis

Data were summarised using the random-effects model although the fixed-effect model was also analysed to ensure robustness of the model chosen and susceptibility to outliers.

Subgroup analysis and investigation of heterogeneity

Subgroup analysis was used to explore possible sources of heterogeneity (e.g. study duration, participants, interventions and study quality). Heterogeneity among participants may have been related to age and renal pathology. Heterogeneity in treatments may have been related to prior agents used and the agent, dose and duration of therapy (Table 1).

Table 1. Summary of analyses
  1. CrCl - creatinine clearance; IQR - interquartile range; PET - peritoneal equilibration test; PD - peritoneal dialysis; RRF - residual renal function

OutcomeSubgroup analyses performed‘Other data’ tables
Neutral pH, low GDP PD solution versus conventional PD solution
RRF
  • Study duration

  • Incident vs prevalent patients

  • Single vs multicentre study

  • Parallel vs cross-over design

  • PD fluid types

  • Presence of selection bias

  • Presence of other significant bias

  • Weekly residual GFR in patients with baseline GFR > 2 mL/ min/ 1.73 m²

 
Urine volume
  • Study duration

  • Standard vs hypertonic PET

  • Single vs multicentre study

  • Parallel vs cross-over design

  • Presence of selection bias

  • Presence of other significant bias

 
Development of anuria  
 4-hour peritoneal UF
  • Study duration

  • Standard vs hypertonic PET

  • Single vs multicentre study

  • Parallel vs cross-over design

  • Presence of selection bias

  • Presence of other significant bias

 
Daily peritoneal UF
  • Study duration

  • Incident vs prevalent patients

  • Single vs multicentre study

  • Parallel vs cross-over design

  • Presence of selection bias

  • Presence of other significant bias

 
Peritoneal solute transport rate (4-hour dialysate:plasma creatinine)
  • Study duration

  • Presence of selection bias

  • Presence of other significant bias

 
 Dialysis adequacy (CrCl/ Kt/V urea)  Dialysis adequacy and peritoneal transport in anuric patients (median (IQR))
Inflow pain  
Peritonitis
  • Presence of selection bias

  • Presence of attrition bias

  • Presence of other significant bias

 
Technique failure  
Hospitalisation  
All-cause mortality  
Glucose polymer (icodextrin) versus conventional PD solution
Uncontrolled fluid overload  
Rash  
RRF  
Urine volume Change in urine volume (mL)
Daily peritoneal UFChange in UF volume/ membrane transport characteristics 
Peritoneal solute transport rate (4-hour dialysate:plasma creatinine)  
Dialysis adequacy (CrCl)Change in peritoneal CrCl/membrane transport characteristics 
Peritonitis  
Technique failure  
All-cause mortality  

Lactate-buffered and bicarbonate (± lactate)-buffered neutral pH low GDP PD solutions were grouped as initial analyses did not identify any significant differences in their effects. Separate analyses were performed for glucose polymer (icodextrin) solutions and glucose-based biocompatible fluids due to anticipated difference in outcome.

Sensitivity analysis

Where sufficient studies were available we investigated the following:

  • study duration

  • incident versus prevalent patients

  • single versus multicentre studies

  • parallel versus cross-over design

  • PD fluid types

  • presence of selection bias

  • presence of other significant bias

  • weekly residual GFR in patients with baseline GFR > 2 mL/min/1.73 m².

Results

Description of studies

Results of the search

The literature search retrieved 172 reports after removal of duplicates. Analysis of the 172 reports identified 36 studies (2719 patients) published in 111 reports that were eligible and included in this review. The search results are summarised in Figure 1.

Figure 1.

Study flow diagram.

Included studies

Twenty-four studies examined the effect of neutral pH, low GDP PD solution against conventional PD solutions (Bajo 2011; balANZ Trial 2006; Cancarini 1998; Carrasco 2001; Choi 2008; Cnossen 2011; Coles 1997; DIUREST Study 2010; EURO-BALANCE Study 2004; Fan 2008; Feriani 1998; Fernandez-Perpen 2012; Fusshoeller 2004; Kim 2003; Kim 2008; Lai 2012a; Mactier 1998; Pajek 2008; Rippe 2001; Schmitt 2002; Szeto 2007; Tranaeus 2000; Weiss 2009; Zeier 2003). Of these, 14 studies (1047 patients) evaluated lactate-buffered neutral pH, low GDP PD solutions (Bajo 2011; balANZ Trial 2006; Carrasco 2001; Choi 2008; Cnossen 2011; DIUREST Study 2010; EURO-BALANCE Study 2004; Fan 2008; Kim 2003; Kim 2008; Rippe 2001; Lai 2012a; Szeto 2007; Zeier 2003). Ten studies (441 patients) included bicarbonate (± lactate)-buffered PD solutions (Cancarini 1998; Coles 1997; Feriani 1998; Fernandez-Perpen 2012; Fusshoeller 2004; Mactier 1998; Pajek 2008; Schmitt 2002; Tranaeus 2000; Weiss 2009). Only one (31 patients) of the 10 studies using bicarbonate (± lactate)-buffered low GPD PD solution examined outcomes exclusively in incident patients. Twelve studies (1231 patients) assessed clinical outcomes of using icodextrin in one PD exchange daily to conventional PD solution use (Bredie 2001; Davies 2003; di Paolo 2000; Finkelstein 2005; Konings 2003; Lin 2009a; MIDAS Study; Paniagua 2008; Plum 2002; Posthuma 1997; Takatori 2011; Wolfson 2002). Of these, three studies assessed the effect of icodextrin in patients with high or high average membrane transport characteristics (Davies 2003; Finkelstein 2005; Paniagua 2008).

Excluded studies

Reasons for exclusion of studies include studies not RCTs, assessed effect of amino acid-based PD solution, duplicate reports, and comparison of two regimens of the same biocompatible PD solution.

Risk of bias in included studies

Risk of bias domains of the included studies are shown in Figure 2.

Figure 2.

Risk of bias graph: review authors' judgements about each risk of bias item

Allocation

Allocation methods and concealment were generally incompletely reported and therefore difficult to assess. Allocation concealment was adequate in 11 studies (30%).

Blinding

Nineteen studies (53%) were classified as low risk of performance bias. However, only three studies (8%) were double-blind in design, at low risk of detection bias.

Incomplete outcome data

Intention-to-treat analysis was performed in twenty studies (56%). Patients lost to follow-up ranged from 0% to 83.4%.

Selective reporting

Selective reporting was observed in thirteen studies (36%).

Other potential sources of bias

Other significant biases were identified in six studies (17%). The potential sources of bias included, use of different types of neutral pH, low GDP PD solutions in the intervention group (two studies), potential centre-related effects (one study), different characteristics at baseline between patients in intervention and control groups (three studies), unclear description of participant details (one study).

Effects of interventions

See: Summary of findings for the main comparison; Summary of findings 2

There were no significant differences in results of analyses performed using random and fixed-effects models. The results presented below therefore refer to those obtained using a random-effects model. Quantitative analyses with high levels of heterogeneity (I² ≥ 75%) were not reported.

Neutral pH, low GDP versus conventional glucose PD solution

Residual renal function

Improved preservation of RRF with the use of low GDP PD solution was evident once follow-up reached 12 to 24 months (Analysis 1.1 (6 studies, 360 patients): SMD 0.31, 95% CI 0.10 to 0.52, P = 0.004; I² = 0%) and more than 24 months (Analysis 1.2 (5 studies, 279 patients): SMD 0.25, 95% CI 0.01 to 0.48, P = 0.04; I² = 0%). This approximated to MD in GFR of 0.84 mL/min/1.73 m² (95% CI 0.23 to 1.45) and 0.70 mL/min/1.73 m² (95% CI 0.06 to 1.33), respectively. There was no significant reduction in the risk of RRF decline in studies with less than eight months follow-up (Analysis 1.3 (7 studies, 395 patients): SMD 0.16, 95% CI -0.09 to 0.4, P = 0.2; I² = 30%). Similarly, the overall effect was not significant (Analysis 1.4 (11 studies, 564 patients): SMD: 0.16, 95% CI -0.01 to 0.32, P = 0.06; I² = 0%). Further subgroup analyses based on study design, patient characteristics, and quality assessment did not influence the outcome. A subgroup analysis based on the type of PD solution used was not helpful as the majority of the studies were performed using Balance® PD solutions (Analysis 1.5). A funnel plot showed no evidence of asymmetry, although the possibility of publication bias cannot be excluded given the small number of studies.

Urine volume

Twenty-four hour urine volume was significantly greater with the use of neutral pH, low GPD PD solution (Analysis 1.6 (7 studies, 520 patients): MD 126.39 mL/d, 95% CI 26.73 to 226.05, P = 0.01; I² = 20%). As with RRF, differences in urine volume reached a significance level once the study duration continued beyond 12 months: 12 months to 24 months (Analysis 1.7 (4 studies, 297 patients): MD 148.93 mL/d, 95% CI 64.92 to 232.95, P < 0.01; I² = 0%); > 24 months (Analysis 1.8 (2 studies, 215 patients): MD 193.17 mL/d, 95% CI 8.83 to 377.52, P = 0.04; I² = 0%). Multi-centre studies were more likely to report an increase in urine volume with use of neutral pH, low GDP PD solution (Analysis 1.9 (5 studies, 379 patients): MD 159.22 mL/d, 95% CI 78.11 to 240.32, P < 0.01; I² = 20%). Subgroup analysis according to brand of neutral pH, low GDP solution showed that Balance® was the only solution with significant improvement in urine volume. However these studies were also those with longer follow-up duration (Analysis 1.10 (4 studies, 275 patients): MD 141.09 mL/d, 95% CI 57.92 to 224.27, P < 0.01; I² = 20%). Incidence of anuria was reported by only one study, which showed significant improvement with the use of neutral pH, low GDP PD solution (Analysis 1.11 (1 study, 192 patients): RR 0.33, 95% CI 0.14 to 0.80). This study also reported a longer mean time to development of anuria with low GDP solution.

Peritoneal ultrafiltration

The overall four-hour peritoneal UF during peritoneal equilibration test was similar between the neutral pH, low GDP and conventional PD solutions (Analysis 1.12 (6 studies, 196 patients): SMD -0.28, 95% CI -0.67 to 0.10, P = 0.2; I² = 28%; estimated MD -59.25 mL/4 hours, 95% CI -141.11 to 22.61). Similarly, the 24-hour peritoneal UF was comparable (Analysis 1.13 (7 studies, 451 patients): SMD -0.23, 95% CI -0.62 to 0.16; P = 0.3; estimated MD -138.57 mL/d, 95% CI -382.12 to 104.98), although a moderate to high level of heterogeneity was observed (I² = 74%, P < 0.01). Heterogeneity was unable to be explained by differences in study population or setting, study design or risk of bias. Only a small number of studies disclosed the status of icodextrin use during the study.

Peritoneal solute transport rate

There was no statistically significant difference in the four-hour D/PCreat measured during peritoneal equilibration test (Analysis 1.14 (5 studies, 363 patients): MD 0.01, 95% CI -0.02 to 0.04, P = 0.4; I² = 41%). However, the EURO-BALANCE Study 2004 reported higher median four-hour D/PCreat in the conventional PD solution group (0.66, IQR 0.59 to 0.76) compared to the neutral pH, low GDP PD solution group (0.59, IQR 0.58 to 0.63; Analysis 1.15). Similarly, balANZ Trial 2006 reported relatively preserved four-hour D/PCreat in the neutral pH, low GDP PD solution group whilst the level consistently and significantly increased in the conventional PD solution group over their 24 month follow-up period.

Peritoneal small solute clearance

There was no significant difference between low GDP PD solution and conventional PD solution in terms of peritoneal CrCl (Analysis 1.16 (6 studies, 400 patients): MD -0.25 L/wk/1.73 m², 95% CI -2.05 to 1.55, P = 0.8; I² = 0%) or Kt/V of urea (Analysis 1.17 (5 studies, 312 patients): MD 0.00, 95% CI -0.10 to 0.11, P = 0.9; I² = 26%).

Peritonitis

The use of neutral pH, low GDP PD solution did not result in significant differences in either the proportion of patients experiencing at least one peritonitis episode (Analysis 1.18 (8 studies, 631 patients): RR 1.26, 95% CI 0.87 to 1.81, P = 0.2) or overall peritonitis rate (Analysis 1.19 (6 studies, 13,802 patient-months): RR 1.13, 95% CI 0.77 to 1.66, P = 0.5). Moderate level heterogeneity was identified (I² = 64%; P = 0.02), and was unable to be explained by differences in study characteristics. However, when studies were analysed according to their risk of attrition bias, only one study was classified as low risk (balANZ Trial 2006), which was also the only study that showed decreased peritonitis incidence with the use of neutral pH, low GDP PD solutions (Analysis 1.20.1 (1 study, 182 patients): RR 0.60, 95% CI 0.41 to 0.88). Due to different approaches in reporting peritonitis rates, ability to perform comprehensive quantitative analysis was restricted (Table 2; Table 3). For example, the quantitative analysis excluded findings from Tranaeus 2000, who reported a significant decrease in peritonitis rates with the use of low GDP PD solution, with 12 month peritonitis rates of 0.24 episodes/patient-year compared to 0.63 episodes/patient-year with the use of conventional PD solution (Table 2).

Table 2. Peritonitis rate (episodes/patient-year): neutral pH, low GDP PD solutions versus conventional PD solutions
StudyTreatment groupPeritonitis rate
balANZ Trial 2006Standard fluids0.49
Low-GDP fluids0.30
Fan 2008

Extension study from Srivastava

Standard fluids

0.45
Low-GDP fluids0.52
Kim 2008Standard fluids

0.09 (12 months)

0.06 (24 months)

Low-GDP fluids

0.24 (12 months)

0.19 (24 months)

Rippe 2001Standard fluids0.467
Low-GDP fluids0.555
Tranaeus 2000Standard fluids

0.52 (6 months)

0.63 (12 months)

Low-GDP fluids

0.46 (6 months)

0.24 (12 months)

Table 3. Peritonitis rate (patient-months/episode): neutral pH, low GDP PD solutions versus conventional PD solutions
Study IDStandard glucose solutionLow GDP, neutral pH solution
Bajo 20111:271:16
DIUREST Study 20101:39.71:36.4
Fan 2008

1:47.2

1:31.5

1:36

1:33.7 (extension study)

Feriani 19981:201:17
Fernandez-Perpen 20121:301:25
Tranaeus 20001:191:51
Inflow pain

There was a trend towards decreased incidence of inflow pain with the use of neutral pH, low GDP PD solutions (Analysis 1.21 (1 study, 58 patients): RR 0.51, 95% CI 0.24 to 1.08, P = 0.08). Two additional cross-over design RCTs reported significantly lowered risk of inflow pain with its use (Fusshoeller 2004; Mactier 1998). In particular, buffer-dependent differences in the effects of neutral pH, low GDP PD solutions on inflow pain were reported by Mactier 1998, favouring bicarbonate/lactate-buffered PD solution over purely bicarbonate-buffered PD solution. These latter two cross-over design studies were excluded from meta-analysis due to inability to isolate data from the first arm of the study.

Hospitalisation

Use of neutral pH, low GPD PD solution did not have a significant effect on hospitalisation duration compared with use of conventional solution (Analysis 1.22 (2 studies, 230 patients): MD 3.02 days, 95% CI -7.08 to 13.12, P = 0.6; I² = 45%).

Technique failure

Death censored technique failure was not different between patients receiving neutral pH, low GDP PD solution and those receiving conventional solution (Analysis 1.23 (12 studies, 968 patients): RR 1.04, 95% CI 0.60 to 1.78, P = 0.9; I² = 9%).

Patient survival

Use of neutral pH, low GDP PD solution did not have a significant effect on all-cause mortality (Analysis 1.24 (11 studies, 858 patients): RR 0.78, 95% CI 0.48 to 1.29; P = 0.3; I² = 0%).

Adverse events

Six studies reported comparable incidence of adverse events with the use of neutral pH, low GDP PD solutions (balANZ Trial 2006; Coles 1997; EURO-BALANCE Study 2004; Feriani 1998; Schmitt 2002; Tranaeus 2000) (Table 4).

Table 4. Adverse effects reported in studies
  1. UF - ultrafiltration

Adverse event Standard glucose solution Low GDP solution Studies reporting outcome
No. events No. at risk No. events No. at risk
Neutral pH, low GDP PD solution (excluding peritonitis, mortality)
Exit site infection714612168

balANZ Trial 2006

Coles 1997

Feriani 1998

Tunnel infection291191 balANZ Trial 2006
Non-PD related infection/ general infection

20

 

11010131

balANZ Trial 2006

Coles 1997

Inadequate dialysis191191 balANZ Trial 2006
Fluid overload/ hypervolaemia

6

 

1465168

balANZ Trial 2006

Coles 1997

Feriani 1998

Hypertension355377

Coles 1997

Feriani 1998

Hypotension036137 Feriani 1998
Hernia12127

10

 

128

balANZ Trial 2006

Feriani 1998

Peritoneal leak391191 balANZ Trial 2006
Catheter blockage491591 balANZ Trial 2006
Malposition291191 balANZ Trial 2006
Gastrointestinal disorder6911491 balANZ Trial 2006
Abdominal pain019340 Coles 1997
Pancreatitis136037 Feriani 1998
Enteritis036237 Feriani 1998
Vomiting036137 Feriani 1998
Newly diagnosed cancer391491 balANZ Trial 2006
Arthritis136037 Feriani 1998
Angina036137 Feriani 1998
Apoplexy136137 Feriani 1998
Hypercalcaemia355577

Coles 1997

Feriani 1998

Hypocalcaemia019340 Coles 1997
Hyperphosphataemia319440 Coles 1997
Hyperglycaemia136037 Feriani 1998
Glucose polymer (icodextrin) (excluding rash, peritonitis, mortality)
Abdominal discomfort1103098 Lin 2009a
Anaemia5014145205

Paniagua 2008

Wolfson 2002

Arterial emboli11030106 MIDAS Study
Cardiac failure11031106 MIDAS Study
Cerebrovascular accident01032106 MIDAS Study
Diabetic foot529130 Paniagua 2008
Dizzy0103198 Lin 2009a
Electrolyte disturbances429130 Paniagua 2008
Exit site infection2411228175 Wolfson 2002
Fatigue0103298 Lin 2009a
Fluid overload171326136

Lin 2009a

Paniagua 2008

Headache911225175 Wolfson 2002
Hyperglycaemia2729830 Paniagua 2008
Hypotension2821525273

Lin 2009a

Wolfson 2002

Myocardial infarction71322136

MIDAS Study

Paniagua 2008

Pain1811230175 Wolfson 2002
Pleural effusion629130 Paniagua 2008
Pneumonia01031106 MIDAS Study
Pulmonary embolism01031106 MIDAS Study
Thirsty0103198 Lin 2009a
Uncontrolled hypertension2121541281

MIDAS Study

Wolfson 2002

Upper respiratory tract infection2511241175 Wolfson 2002
Vomiting1103098 Lin 2009a

Glucose polymer (icodextrin) versus convention glucose PD solution

Peritoneal ultrafiltration

Use of icodextrin uniformly resulted in improved peritoneal UF compared with glucose exchanges (Analysis 2.1 (4 studies, 102 patients): MD 448.54 mL/d, 95% CI 289.28 to 607.80, P < 0.01; I² = 0%). However, this outcome may have been biased in favour of icodextrin as only one of these four studies allowed the use of hypertonic glucose PD solution (3.86%) in the control group. Nonetheless, superior peritoneal UF was reported in Finkelstein 2005 where icodextrin was compared to 4.25% glucose PD solution in 92 APD patients with higher peritoneal solute transport rate (defined as four-hour D/PCreat > 0.7), and UF failure (defined as four-hour net UF < 100 mL using 2.5% dextrose). Following two weeks therapy, net UF volumes were +373.8 ± 58.9 mL/d in the icodextrin group and -239.7 mL ± 151.0 mL/d in the controls. Similarly, when the use of icodextrin was compared to 2.5% glucose PD solution according to the peritoneal equilibration test category, Lin 2009a identified significant increases in UF capacities in all patients except low transporters. Patients with higher peritoneal transport characteristics derived greater UF benefit.

Episodes of uncontrolled fluid overload

Use of icodextrin led to significant reduction in reported episodes of uncontrolled fluid overload (Analysis 2.2 (2 studies, 100 patients): RR 0.30, 95% CI 0.15 to 0.59, P < 0.01; I² = 0%).

Residual renal function

Icodextrin had no appreciable impact on RRF (Analysis 2.3 (4 studies, 114 patients): SMD 0.12, 95% CI -0.26 to 0.49, P = 0.5; I² = 0%). This approximated to MD in renal CrCl of 0.50 mL/min (95% CI -0.71 to 1.71).

Urine volume

Icodextrin-induced increases in peritoneal UF volumes were not associated with any significant changes in daily urine volumes (Analysis 2.4 (3 studies, 69 patients): MD -88.88 mL/d, 95% CI -356.88 to 179.12, P = 0.5; I² = 0%). In fact, Davies 2003 reported better maintenance of urine volume with the use of icodextrin at six months when compared to 2.27% dextrose PD solution use (Analysis 2.5).

Peritoneal small solute clearance

The overall effect of icodextrin on peritoneal CrCl was not significant (Analysis 2.6 (3 studies, 237 patients): SMD 0.36, 95% CI -0.24 to 0.96; P = 0.2; I² = 66%; estimated MD 0.38 mL/min 95% CI 0.13 to 0.64). Moderate to severe heterogeneity was observed and appeared to be related to study design variability. Two studies were open-label in design with unclear description of the number of patients in each peritoneal equilibration test category (Plum 2002; Posthuma 1997). Similar to their findings with peritoneal UF, Lin 2009a reported significantly greater peritoneal CrCl measurements in all patients except low transporters.

Peritonitis

Use of icodextrin was not associated with any significant changes in peritonitis risk (Analysis 2.7 (5 studies, 607 patients): RR 0.97, 95% CI 0.76 to 1.23, P = 0.8; I² = 15%).

Adverse events

The risk of rash (Analysis 2.8 (3 studies, 755 patients): RR 2.51, 95% CI 0.59 to 10.72, P = 0.2; I² = 38%) was not increased with icodextrin use compared with glucose exchanges. Four studies reported comparable incidence of adverse events with the use of icodextrin (Lin 2009a; MIDAS Study; Paniagua 2008; Wolfson 2002) (Table 4).

Technique failure

None of the studies were adequately powered to assess this outcome, with the majority having follow-up duration of less than six months. Within these constraints, the use of icodextrin did not significantly influence technique survival (Analysis 2.9 (3 studies, 290 patients): RR 0.58, 95% CI 0.28 to 1.20, P = 0.1; I² = 0%).

Patient survival

In the context of low event numbers and short follow-up durations, patient survival was not significantly different between individuals receiving icodextrin and those receiving standard glucose solution (Analysis 2.10 (6 studies, 816 patients): RR 0.82, 95% CI 0.32 to 2.13, P = 0.7; I² = 0%).

Discussion

Summary of main results

This systematic review demonstrated that the use of neutral pH, low GDP PD solution resulted in maintenance of higher levels of urine output and RRF over time, particularly beyond 12 months of treatment using these PD solutions. Its impact on inflow pain was at least comparable if not superior compared to standard glucose PD solutions. However, neutral pH, low GDP PD solution was not observed to exert significant effects on peritoneal UF or hospitalisation. In contrast, the use of icodextrin in one PD exchange daily led to significantly increased peritoneal UF volumes and a lower risk of uncontrolled fluid overload compared with glucose PD exchanges alone. These benefits were more pronounced in patients with higher peritoneal solute transport rates and extended to individuals with identified UF failure. The augmentation of peritoneal UF was not associated with any significant changes in residual renal clearance or urine volume. Neither neutral pH, low GDP PD solution nor icodextrin use was associated with significant changes in peritoneal solute transport rate, peritoneal small solute clearance, and technique survival or patient survival.

Overall completeness and applicability of evidence

In the present study, the use of neutral pH, low GDP fluids were found to exert beneficial effects on RRF, as evidenced by higher levels of residual renal clearance and urine volumes, particularly when the solutions were used for periods in excess of 12 months. Such effects are biologically plausible since GDPs have been demonstrated to exert direct nephrotoxic effects on renal tubular cells (Justo 2005). Although currently available neutral pH, low GDP fluids vary considerably in their GDP content (Feriani 2009; Lage 2000; Mortier 2004b), the bulk of the studies analysed used one particular solution (Balance®, Fresenius Medical Care, Bad Homburg, Germany; Bajo 2011; balANZ Trial 2006; Choi 2008; EURO-BALANCE Study 2004; Kim 2003; Kim 2008; Szeto 2007), such that comparison of the renoprotective benefits of different neutral pH, low GDP PD solutions was not possible. Nevertheless, improved preservation of RRF and urine volume with the use of neutral pH, low GDP fluids were clinically significant. Bargman 2001 previously reported that for each 5 L/wk/1.73 m² increment in GFR and every 250 mL increase in urine volume there was an associated 12% and 36% decrease in risk of mortality in PD patients, respectively. This review observed that at 24 months there was a GFR increment equivalent to approximately 7 L/wk/1.73 m² and overall improvement in urine volume of 126.35 mL/d.

It has been suggested that the observed benefits of neutral pH, low GDP PD solutions on RRF may be explained by reductions in peritoneal UF leading to increased urine volume and residual renal clearance (Bargman 2010). Our review found that neither four-hour peritoneal equilibration test nor daily peritoneal UF was significantly different between the neutral pH, low GDP PD solution group and the conventional PD solution group. It should be noted however that the analysis of daily peritoneal UF suffered from a moderate to high levels of statistical heterogeneity, which could not be satisfactorily explained. This may have been due to a high level of clinical heterogeneity from universally open-label design RCTs that were at risk of co-intervention bias. The interpretation of the findings was further hindered by a frequent lack of disclosure of icodextrin use (Kim 2008; Lai 2012a; Rippe 2001; Schmitt 2002; Weiss 2009) or peritoneal glucose exposure (Lai 2012a). In the context of these uncertainties, the four-hour peritoneal UF volumes from the peritoneal equilibration test were likely to have provided the most accurate reflection of patients' UF capacities and, indeed, did not demonstrate appreciable evidence of heterogeneity.

A lack of effect of neutral pH, low GDP PD solutions on peritoneal UF was supported by the findings of comparable final peritoneal solute transport rate between the intervention and control groups. During the course of the studies, a number of studies reported no difference in peritoneal solute transport rate between the groups over time (Choi 2008; Fan 2008; Lai 2012a), whilst the largest study, the balANZ Trial 2006, reported relatively preserved peritoneal solute transport rate values in the neutral pH, low GDP PD solution group, whilst peritoneal solute transport rate consistently and significantly increased in the control PD solution group over the 24 month follow-up period. The outcome of this study highlights the need to carefully assess the trend in peritoneal solute transport rate over time, rather than just an absolute value at the end of the study. Importantly, higher peritoneal solute transport rate has been recognised as a significant risk factor for both mortality and technique failure in a number of large observational studies (Churchill 1998; Davies 1998; Fried 1997; Rumpsfeld 2006).

Although GDP in PD solutions has been implicated in promotion of nephrotoxicity and peritoneal membrane injury (Mortier 2004b; Justo 2005; Witowski 2001), inflow pain, which is reported to occur in up to 73% of PD patients, has been attributed to the acidic pH of conventional solutions (Vaamonde 1975). Use of neutral pH solution appears to effectively alleviate this problem. The trend towards benefit of neutral pH, low GDP fluids on inflow pain in this study supports the common practice of using these fluids for this clinical indication. Nevertheless, the results of the present review should be interpreted cautiously as the study included in the meta-analysis was not blinded (Rippe 2001). Consequently, the results may have been potentially influenced by observation and performance biases. Furthermore, one of the cross-over design studies reported appreciable variation in the frequency of inflow pain amongst the nine participating centres, raising the possibility of confounding centre effects (Mactier 1998).

A noteworthy finding of this review was that neutral pH, low GDP fluids appeared to exert no significant effect on either the proportion of individuals experiencing peritonitis or overall peritonitis rates. This issue has become highly topical with the recent reporting of balANZ Trial 2006 finding that neutral pH, low GDP fluid use was associated with a 50% reduction in time to first peritonitis episodes and a 36% reduction in overall peritonitis rates compared with conventional solution. The suggested explanation for this finding was improved peritoneal host defence mechanisms, given that there was considerable experimental evidence that neutral pH, low GDP fluids significantly improved viability and function of peritoneal mesothelial cells, leukocytes and macrophages (Boulanger 2002; Jorres 1998; Mortier 2003; Schambye 1996; Topley 1997; Witowski 2005). A similar beneficial effect of biocompatible PD fluid on peritonitis rates had also been reported following extended follow-up in another study (Tranaeus 2000). In contrast, most investigations, which were small and underpowered, found no effect on biocompatible PD solutions on peritonitis risk (Bajo 2011; Choi 2008; Coles 1997; DIUREST Study 2010; Fan 2008; Feriani 1998; Fernandez-Perpen 2012; Kim 2008; Rippe 2001). Perhaps not surprisingly, when all of these studies were combined in a meta-analysis, significant heterogeneity was observed. The reasons for this heterogeneity were unable to be determined in this review. Consequently, the effect of neutral pH, low GDP PD solution on peritonitis risk in PD patients remains uncertain and further adequately powered, well-designed randomised studies are warranted.

The demonstrated benefit of icodextrin with respect to augmented peritoneal UF in the present review was seen in both short-term and long-term studies (up to 24 months) and when compared to various concentrations of glucose PD solutions, including hypertonic exchanges. For instance, Finkelstein 2005 observed a net change in UF volume of 401.6 ± 79 mL/d in the icodextrin group compared to -6.98 ± 57.2 mL/d in the 4.25% glucose group at two weeks. Importantly, the UF benefit of icodextrin extended to patients with UF failure was superior to 4.25% glucose PD solution use (+373.8 ± 58.9 mL/d versus -239.7 ± 151.0 mL/d, respectively; Finkelstein 2005). Similarly, the subgroup analysis of the two studies (Posthuma 1997; Takatori 2011) with the longest follow-up (24 months; Analysis 2.1) showed a MD of 510.55 mL/d (95% CI 10.10 to 1011, P = 0.05), in favour of icodextrin. The findings of this systematic review therefore support the recommendations of the International Society of Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis that icodextrin should be used in the long dwell of patients who are identified to have high peritoneal solute transport rate or UF failure (Mujais 2000).

Given that manipulation of peritoneal UF via various interventions has not infrequently been reported to induce reciprocal changes in urine volume and residual renal clearance measurements (Bargman 2010; Davies 2009), these outcomes were specifically examined in the present review and found not to be compromised by icodextrin-enhanced peritoneal UF.

Similarly, the additional fluid volume removed via the peritoneal cavity with icodextrin was not associated with increased peritoneal small solute clearance measurements. It should be noted however that moderate to severe study heterogeneity was detected, primarily related to variability in the peritoneal membrane transport characteristics of patients included in each study. Indeed, significant enhancement of small solute clearance with icodextrin use was reported by two studies, with benefit seen only in those individuals with higher peritoneal solute transport rate (Finkelstein 2005; Lin 2009a). Further studies are therefore warranted to examine the effects of icodextrin on peritoneal small solute clearance according to peritoneal transport status.

Reassuringly, icodextrin was not found to be associated with significantly increased harm compared with glucose exchanges alone. Skin rash was the most commonly reported adverse event, which led to cessation of icodextrin in 0% to 4.3% of patients (Finkelstein 2005; Lin 2009a; Wolfson 2002) across the identified studies. However, no study reported occurrence of rash severe enough to warrant hospitalisation or additional therapeutic interventions other than cessation of icodextrin. It is unknown whether any of these patients were subsequently re-challenged using icodextrin. Similarly, six studies reported comparable incidence of adverse events with the use of neutral pH, low GDP PD solutions compared to conventional PD solutions (balANZ Trial 2006; Coles 1997; EURO-BALANCE Study 2004; Feriani 1998; Schmitt 2002; Tranaeus 2000).

Despite finding significant and clinically important improvements with the use of neutral pH, low GDP PD solution and icodextrin, neither type of PD solution was associated with improvements in technique survival or patient survival. However, the number of events in the meta-analysis was small, indicating that the review was under-powered to address these important outcomes.

Quality of the evidence

The present review suffers from several limitations that relate largely to potential risk of bias in the included studies. Many studies failed to specify method of randomisation, allocation concealment and blinding of outcome assessors. It was often difficult to determine whether data were truly analysed on an intention-to-treat analysis and how the study dealt with the dropouts. The current review was unable to identify any significant harm associated with the use of biocompatible PD solutions, but it should be noted that adverse events were not uniformly reported by studies. In general, RCTs were limited by small participant numbers, large dropout rates, use of biocompatible PD solutions with variable GDP concentrations and open-label study designs. It should also be noted that a large proportion of studies (27/36, 75%) received funding sponsorship from the pharmaceutical industry. The resultant risk of bias was generally unclear. In particular the balANZ Trial 2006, which received industry funding and contributed the largest number of patients, was designed primarily by clinicians hence risk of bias low. Furthermore, a lack of standardised approach in reporting outcomes, such as peritonitis or RRF, created challenges for performing more inclusive, quantitative analyses. These barriers could have increased the risk of statistical error and reduced the strength of the conclusions drawn in this review. 

Potential biases in the review process

The strength of this review is that it represents a comprehensive systematic review based on a previous publication of a detailed protocol, a thorough MEDLINE, EMBASE, risk of bias assessment and CENTRAL search and inclusion of only RCTs or quasi-RCTs as pre-specified. Only the data from the first phase of the cross-over RCTs were included for quantitative analyses in order to minimise the risk of the carry-over effect and potential introduction of bias on the time-dependent variables. Data extraction, data analysis, and method quality assessment were performed by two independent investigators, and any differences in consensus were checked with an additional two authors. Peritonitis outcomes were examined separately in terms of rates per patient-month and number of patients affected to maximise statistical power and to incorporate studies more comprehensively to account for non-standardised approach to reporting peritonitis across studies. 

Agreements and disagreements with other studies or reviews

To the best of our knowledge, this is the first published systematic review of RCTs of both neutral pH, low GDP PD solution and icodextrin. To date, there has been one meta-analysis of icodextrin (Qi 2011), and the results from the present review differ somewhat from the earlier meta-analysis. Specifically, although both studies observed icodextrin use was associated with a significant augmentation of peritoneal UF, only the current systematic review examined the outcome of uncontrolled fluid overload and found a significant benefit of icodextrin. Technique survival was also only examined in the present study and found to be comparable between the icodextrin and glucose groups. Other limitations of the previous review by Qi 2011, which did not apply to the current study, included restrictive selection criteria (exclusion of first phase of cross-over studies, incident patients, paediatric patients, studies with < 10 patients, studies not published in English) and exclusive reporting of outcomes using a fixed-effects model. In contrast, the present review adopted a random-effects model to account for the presence of clinical heterogeneity and included two additional studies including the first phase of a randomised cross-over study (Bredie 2001), and data from a recently published RCT, which had the longest follow-up duration (24 months) of all icodextrin studies (Takatori 2011).

In conclusion, this systematic review shows that: (1) based on seven studies, neutral pH, low GDP PD solution resulted in better preservation of urine output which was increasingly apparent with longer therapy duration; (2) based on five studies, neutral pH, low GDP PD solution resulted in better preservation of RRF, which became significant once therapy duration reached 12 months or more; and (3) based on one study, use of neutral pH, low GDP PD solution led to a trend towards improvement in inflow pain, which was further favourably confirmed by outcomes from two cross-over design RCTs. However, these benefits did not translate into decreased peritonitis episodes, improved technique survival or patient survival; (4) based on four studies, the use of icodextrin improved peritoneal UF which translated into a decrease in episodes of uncontrolled fluid overload from two studies. The benefit extended to patients with high peritoneal solute transport rate and UF failure. Icodextrin use was not associated with any significant changes in residual renal clearance, urine volume peritoneal solute transport rate or peritoneal small solute clearance, and did not translate into improved technique survival or patient survival. This review did not find any significant harm resulting from the use of either type of PD solution. Therefore, based on the best available evidence, the use of biocompatible PD solution resulted in some clinically relevant benefits without added risks of harm. Larger studies are needed for accurate evaluation of the impact of these solutions on patient-level ('hard') outcomes, such as peritonitis, technique survival and patient survival.

Authors' conclusions

Implications for practice

  • In PD patients with preserved RRF, use of neutral pH, low GDP PD solutions may optimise maintenance of RRF and urine output, which becomes more apparent with longer therapy duration. At the present time, use of neutral pH, low GDP PD solution should be considered if inflow pain is present.

  • In patients with high, high-average or low-average membrane transport characteristics, icodextrin should be introduced to increase peritoneal UF if clinically indicated to improve fluid status (including patients with UF failure).

  • Currently available evidence from RCTs is inadequate to accurately determine the effects of neutral pH, low GDP PD solutions or icodextrin on many important clinical outcomes including peritonitis, technique survival or patient survival with the use of these PD solutions.

Implications for research

  • Further studies are needed to adequately determine the effect of neutral pH, low GDP PD solution on patient level-outcomes, such as peritonitis and technique survival. These studies should be adequately powered and of sufficient duration. Studies should only include one type of biocompatible PD solution in the treatment group given variable concentrations of GDP amongst available products. This is particularly relevant when examining the effect on peritonitis as different products use different connectology.

  • Specific outcomes to add value would include assessment of change in peritoneal solute transport rate rather than an absolute result to assess the trend in PSTR.

  • Future research should be conducted using standard definitions and clearly state co-interventions used if likely to influence the measured outcome (e.g. icodextrin and peritoneal UF). A comprehensive list of definitions is available from the ISPD guidelines to guide designing future studies.

Acknowledgements

The authors would like to thank Narelle Willis, Leslee Edwards and Ruth Mitchell for their support, comments and advice during the preparation of this protocol. The authors gratefully acknowledge the contribution of Drs Rafael Selgas, Jiaqi Qian, Jun Wada, Kook-Hwan Oh, Antonio Fernandez-Perpen, Claus Peter Schmitt, Mariano Feriani, Adelheid Gauly, who responded to our queries about their studies. David Johnson is a current recipient of a Queensland Government Health Research Fellowship. Yeoungjee Cho is a recipient of 2012 Jacquot Research Entry Scholarship and Australian Postgraduate Award.

Data and analyses

Download statistical data

Comparison 1. Low GDP (all buffer types) versus standard glucose dialysate
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Residual renal function: 12 months up to 24 months6360Std. Mean Difference (IV, Random, 95% CI)0.31 [0.10, 0.52]
1.1 12 months5338Std. Mean Difference (IV, Random, 95% CI)0.31 [0.10, 0.53]
1.2 18 months122Std. Mean Difference (IV, Random, 95% CI)0.27 [-0.57, 1.11]
2 Residual renal function: 24 months and beyond5279Std. Mean Difference (IV, Random, 95% CI)0.25 [0.01, 0.48]
2.1 24 months4154Std. Mean Difference (IV, Random, 95% CI)0.25 [-0.07, 0.57]
2.2 3 years +1125Std. Mean Difference (IV, Random, 95% CI)0.24 [-0.11, 0.59]
3 Residual renal function: up to 12 months7395Std. Mean Difference (IV, Random, 95% CI)0.16 [-0.09, 0.40]
3.1 4 weeks148Std. Mean Difference (IV, Random, 95% CI)0.11 [-0.46, 0.67]
3.2 3 months3143Std. Mean Difference (IV, Random, 95% CI)-0.04 [-0.37, 0.29]
3.3 6 months2113Std. Mean Difference (IV, Random, 95% CI)0.62 [-0.06, 1.31]
3.4 8 months191Std. Mean Difference (IV, Random, 95% CI)-0.03 [-0.44, 0.38]
4 Residual renal function11564Std. Mean Difference (IV, Random, 95% CI)0.16 [-0.01, 0.32]
4.1 3 months3143Std. Mean Difference (IV, Random, 95% CI)-0.04 [-0.37, 0.29]
4.2 12 months3142Std. Mean Difference (IV, Random, 95% CI)0.19 [-0.15, 0.52]
4.3 24 months4154Std. Mean Difference (IV, Random, 95% CI)0.25 [-0.07, 0.57]
4.4 3 years +1125Std. Mean Difference (IV, Random, 95% CI)0.24 [-0.11, 0.59]
5 Residual renal function: PD fluid types11564Std. Mean Difference (IV, Random, 95% CI)0.16 [-0.01, 0.32]
5.1 Balance6288Std. Mean Difference (IV, Random, 95% CI)0.22 [-0.02, 0.45]
5.2 Purely bicarbonate buffered358Std. Mean Difference (IV, Random, 95% CI)0.07 [-0.46, 0.59]
5.3 Multiple fluid types in treatment group2218Std. Mean Difference (IV, Random, 95% CI)0.10 [-0.20, 0.41]
6 Urine volume7520Mean Difference (IV, Random, 95% CI)126.39 [26.73, 226.05]
6.1 3 months2120Mean Difference (IV, Random, 95% CI)-0.54 [-515.46, 514.38]
6.2 12 months3185Mean Difference (IV, Random, 95% CI)144.03 [56.29, 231.77]
6.3 24 months190Mean Difference (IV, Random, 95% CI)115.00 [-146.33, 376.33]
6.4 3 years +1125Mean Difference (IV, Random, 95% CI)270.6 [10.53, 530.67]
7 Urine volume: 12 months to 23 months4297Mean Difference (IV, Random, 95% CI)148.93 [64.92, 232.95]
7.1 12 months3185Mean Difference (IV, Random, 95% CI)144.03 [56.29, 231.77]
7.2 18 months1112Mean Difference (IV, Random, 95% CI)203.0 [-88.41, 494.41]
8 Urine volume: 24 months and beyond2215Mean Difference (IV, Random, 95% CI)193.17 [8.83, 377.52]
8.1 24 months190Mean Difference (IV, Random, 95% CI)115.00 [-146.33, 376.33]
8.2 3 years +1125Mean Difference (IV, Random, 95% CI)270.6 [10.53, 530.67]
9 Urine volume: single/multicentre7520Mean Difference (IV, Random, 95% CI)126.39 [26.73, 226.05]
9.1 Single centre2141Mean Difference (IV, Random, 95% CI)-55.11 [-358.26, 248.04]
9.2 Multicentre5379Mean Difference (IV, Random, 95% CI)159.22 [78.11, 240.32]
10 Urine volume: PD fluid types7520Mean Difference (IV, Random, 95% CI)126.39 [26.73, 226.05]
10.1 Balance4275Mean Difference (IV, Random, 95% CI)141.09 [57.92, 224.27]
10.2 BicaVera127Mean Difference (IV, Random, 95% CI)345.50 [-274.17, 965.17]
10.3 Multiple fluid types in the treatment group2218Mean Difference (IV, Random, 95% CI)37.84 [-423.31, 498.99]
11 Anuria1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
12 Peritoneal ultrafiltration: 4 hours6196Std. Mean Difference (IV, Random, 95% CI)-0.28 [-0.67, 0.10]
12.1 2.26%/2.5% glucose3171Std. Mean Difference (IV, Random, 95% CI)-0.32 [-0.89, 0.25]
12.2 3.86%/4.25% glucose325Std. Mean Difference (IV, Random, 95% CI)-0.30 [-1.17, 0.58]
13 24 hour peritoneal ultrafiltration7451Std. Mean Difference (IV, Random, 95% CI)-0.23 [-0.62, 0.16]
13.1 3 months251Std. Mean Difference (IV, Random, 95% CI)-0.72 [-1.35, -0.09]
13.2 12 months3185Std. Mean Difference (IV, Random, 95% CI)-0.07 [-0.92, 0.78]
13.3 24 months190Std. Mean Difference (IV, Random, 95% CI)0.08 [-0.33, 0.50]
13.4 3 years +1125Std. Mean Difference (IV, Random, 95% CI)-0.30 [-0.66, 0.05]
14 4-hour dialysate:plasma creatinine (2.27%, 2.4%, or 2.5% glucose)5363Mean Difference (IV, Random, 95% CI)0.01 [-0.02, 0.04]
14.1 3 months124Mean Difference (IV, Random, 95% CI)-0.01 [-0.11, 0.09]
14.2 12 months2130Mean Difference (IV, Random, 95% CI)-0.00 [-0.04, 0.03]
14.3 24 months184Mean Difference (IV, Random, 95% CI)0.0 [-0.04, 0.04]
14.4 3 years +1125Mean Difference (IV, Random, 95% CI)0.06 [0.02, 0.10]
15 Dialysis adequacy and peritoneal transport in anuric patients (median (IQR))  Other dataNo numeric data
16 Peritoneal creatinine clearance [L/wk/1.73 m²]6400Mean Difference (IV, Random, 95% CI)-0.25 [-2.05, 1.55]
16.1 3 months124Mean Difference (IV, Random, 95% CI)-7.46 [-20.65, 5.73]
16.2 12 months3163Mean Difference (IV, Random, 95% CI)0.10 [-2.32, 2.52]
16.3 24 months188Mean Difference (IV, Random, 95% CI)-2.60 [-6.80, 1.60]
16.4 3 years +1125Mean Difference (IV, Random, 95% CI)1.30 [-2.37, 4.97]
17 Peritoneal Kt/V urea5312Mean Difference (IV, Random, 95% CI)0.00 [-0.10, 0.11]
17.1 3 months124Mean Difference (IV, Random, 95% CI)-0.01 [-0.78, 0.76]
17.2 12 months3163Mean Difference (IV, Random, 95% CI)0.03 [-0.16, 0.21]
17.3 3 years +1125Mean Difference (IV, Random, 95% CI)-0.04 [-0.18, 0.10]
18 Incidence of peritonitis8631Risk Ratio (M-H, Random, 95% CI)1.26 [0.87, 1.81]
18.1 8 weeks follow-up159Risk Ratio (M-H, Random, 95% CI)1.58 [0.49, 5.10]
18.2 24 weeks173Risk Ratio (M-H, Random, 95% CI)1.17 [0.58, 2.36]
18.3 12 months follow-up2184Risk Ratio (M-H, Random, 95% CI)1.67 [1.14, 2.44]
18.4 18 months follow-up169Risk Ratio (M-H, Random, 95% CI)1.07 [0.56, 2.07]
18.5 24 months follow-up3246Risk Ratio (M-H, Random, 95% CI)1.08 [0.48, 2.45]
19 Peritonitis rate (episodes/total patient-months)613802Risk Ratio (M-H, Random, 95% CI)1.13 [0.77, 1.66]
20 Incidence of peritonitis: attrition bias risk8631Risk Ratio (M-H, Random, 95% CI)1.26 [0.87, 1.81]
20.1 Low risk1182Risk Ratio (M-H, Random, 95% CI)0.6 [0.41, 0.88]
20.2 High risk7449Risk Ratio (M-H, Random, 95% CI)1.50 [1.17, 1.92]
21 Inflow pain1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
21.1 6 months1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
22 Hospitalisation2230Mean Difference (IV, Random, 95% CI)3.02 [-7.08, 13.12]
22.1 12 months148Mean Difference (IV, Random, 95% CI)-0.40 [-6.71, 5.91]
22.2 24 months1182Mean Difference (IV, Random, 95% CI)10.79 [-4.28, 25.86]
23 Technique failure (death-censored)12968Risk Ratio (M-H, Random, 95% CI)1.04 [0.60, 1.78]
23.1 3 months252Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
23.2 6 months2179Risk Ratio (M-H, Random, 95% CI)0.32 [0.04, 2.97]
23.3 12 months3272Risk Ratio (M-H, Random, 95% CI)0.71 [0.12, 4.12]
23.4 24 months4340Risk Ratio (M-H, Random, 95% CI)1.03 [0.50, 2.13]
23.5 3 years +1125Risk Ratio (M-H, Random, 95% CI)2.89 [0.58, 14.33]
24 All-cause mortality11858Risk Ratio (M-H, Random, 95% CI)0.78 [0.48, 1.29]
24.1 3 months252Risk Ratio (M-H, Random, 95% CI)0.16 [0.01, 3.09]
24.2 12 months follow-up4363Risk Ratio (M-H, Random, 95% CI)0.67 [0.26, 1.71]
24.3 18 months follow-up169Risk Ratio (M-H, Random, 95% CI)0.20 [0.02, 1.84]
24.4 24 months follow-up3249Risk Ratio (M-H, Random, 95% CI)1.22 [0.54, 2.77]
24.5 3 years +1125Risk Ratio (M-H, Random, 95% CI)0.77 [0.29, 2.03]
Analysis 1.1.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 1 Residual renal function: 12 months up to 24 months.

Analysis 1.2.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 2 Residual renal function: 24 months and beyond.

Analysis 1.3.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 3 Residual renal function: up to 12 months.

Analysis 1.4.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 4 Residual renal function.

Analysis 1.5.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 5 Residual renal function: PD fluid types.

Analysis 1.6.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 6 Urine volume.

Analysis 1.7.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 7 Urine volume: 12 months to 23 months.

Analysis 1.8.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 8 Urine volume: 24 months and beyond.

Analysis 1.9.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 9 Urine volume: single/multicentre.

Analysis 1.10.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 10 Urine volume: PD fluid types.

Analysis 1.11.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 11 Anuria.

Analysis 1.12.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 12 Peritoneal ultrafiltration: 4 hours.

Analysis 1.13.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 13 24 hour peritoneal ultrafiltration.

Analysis 1.14.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 14 4-hour dialysate:plasma creatinine (2.27%, 2.4%, or 2.5% glucose).

Analysis 1.15.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 15 Dialysis adequacy and peritoneal transport in anuric patients (median (IQR)).

Dialysis adequacy and peritoneal transport in anuric patients (median (IQR))
StudyOutcomeGroup 1: standard (11)Group 2: low GDP (8)
EURO-BALANCE Study 2004Kt/V2.01 (1.78 to 2.1)2.28 (2.04 to 2.5)
EURO-BALANCE Study 2004Total CrCl (mL/wk/1.73 m²)68.7 (63.5 to 70.3)62.9 (58.9 to 69.4)
EURO-BALANCE Study 2004D/P Cr (4 hours)0.66 (0.59 to 0.76)0.59 (0.58 to 0.63)
EURO-BALANCE Study 200424 hour ultrafiltration (mL)1623 (525 to 2350)911 (500 to 1800)
Analysis 1.16.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 16 Peritoneal creatinine clearance [L/wk/1.73 m²].

Analysis 1.17.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 17 Peritoneal Kt/V urea.

Analysis 1.18.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 18 Incidence of peritonitis.

Analysis 1.19.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 19 Peritonitis rate (episodes/total patient-months).

Analysis 1.20.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 20 Incidence of peritonitis: attrition bias risk.

Analysis 1.21.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 21 Inflow pain.

Analysis 1.22.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 22 Hospitalisation.

Analysis 1.23.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 23 Technique failure (death-censored).

Analysis 1.24.

Comparison 1 Low GDP (all buffer types) versus standard glucose dialysate, Outcome 24 All-cause mortality.

Comparison 2. Glucose polymer (icodextrin) versus standard glucose dialysate
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Daily ultrafiltration4102Mean Difference (IV, Random, 95% CI)448.54 [289.28, 607.80]
1.1 3 months133Mean Difference (IV, Random, 95% CI)416.0 [236.26, 595.74]
1.2 4 months132Mean Difference (IV, Random, 95% CI)607.0 [-2164.12, 3378.12]
1.3 24 months237Mean Difference (IV, Random, 95% CI)510.55 [10.10, 1011.00]
2 Uncontrolled fluid overload2100Risk Ratio (M-H, Random, 95% CI)0.30 [0.15, 0.59]
2.1 24 months141Risk Ratio (M-H, Random, 95% CI)0.32 [0.10, 1.01]
2.2 12 months159Risk Ratio (M-H, Random, 95% CI)0.28 [0.12, 0.67]
3 Residual renal function4114Std. Mean Difference (IV, Random, 95% CI)0.12 [-0.26, 0.49]
3.1 Residual GFR (mL/min)132Std. Mean Difference (IV, Random, 95% CI)-0.05 [-0.75, 0.66]
3.2 Renal CrCl (mL/min/1.73 m²)125Std. Mean Difference (IV, Random, 95% CI)0.28 [-0.51, 1.07]
3.3 Renal CrCl (mL/min)124Std. Mean Difference (IV, Random, 95% CI)-0.23 [-1.05, 0.58]
3.4 Residual renal function (mL/min/1.73 m²)133Std. Mean Difference (IV, Random, 95% CI)0.40 [-0.29, 1.09]
4 Urine volume369Mean Difference (IV, Random, 95% CI)-88.88 [-356.88, 179.12]
4.1 4 months132Mean Difference (IV, Random, 95% CI)-35.0 [-2561.49, 2491.49]
4.2 2 years237Mean Difference (IV, Random, 95% CI)-89.49 [-359.01, 180.03]
5 Change in urine volume (mL)  Other dataNo numeric data
6 Peritoneal creatinine clearance3237Std. Mean Difference (IV, Random, 95% CI)0.36 [-0.24, 0.96]
6.1 4 weeks1183Std. Mean Difference (IV, Random, 95% CI)0.07 [-0.22, 0.36]
6.2 3 months133Std. Mean Difference (IV, Random, 95% CI)1.03 [0.30, 1.77]
6.3 12 months121Std. Mean Difference (IV, Random, 95% CI)0.11 [-0.74, 0.97]
7 Episodes of peritonitis5607Risk Ratio (M-H, Random, 95% CI)0.97 [0.76, 1.23]
7.1 4 weeks1201Risk Ratio (M-H, Random, 95% CI)5.25 [0.26, 108.05]
7.2 6 weeks follow-up122Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
7.3 12 months follow-up2346Risk Ratio (M-H, Random, 95% CI)1.05 [0.69, 1.58]
7.4 2 years follow-up138Risk Ratio (M-H, Random, 95% CI)0.88 [0.63, 1.22]
8 Rash3755Risk Ratio (M-H, Random, 95% CI)2.51 [0.59, 10.72]
9 Technique failure (death-censored)3290Risk Ratio (M-H, Random, 95% CI)0.58 [0.28, 1.20]
10 All-cause mortality6816Risk Ratio (M-H, Random, 95% CI)0.82 [0.32, 2.13]
10.1 4 weeks follow-up1201Risk Ratio (M-H, Random, 95% CI)3.15 [0.13, 76.45]
10.2 6 months follow-up2249Risk Ratio (M-H, Random, 95% CI)0.19 [0.01, 4.00]
10.3 12 months1287Risk Ratio (M-H, Random, 95% CI)1.12 [0.34, 3.74]
10.4 2 years follow-up279Risk Ratio (M-H, Random, 95% CI)0.33 [0.04, 3.00]
Analysis 2.1.

Comparison 2 Glucose polymer (icodextrin) versus standard glucose dialysate, Outcome 1 Daily ultrafiltration.

Analysis 2.2.

Comparison 2 Glucose polymer (icodextrin) versus standard glucose dialysate, Outcome 2 Uncontrolled fluid overload.

Analysis 2.3.

Comparison 2 Glucose polymer (icodextrin) versus standard glucose dialysate, Outcome 3 Residual renal function.

Analysis 2.4.

Comparison 2 Glucose polymer (icodextrin) versus standard glucose dialysate, Outcome 4 Urine volume.

Analysis 2.5.

Comparison 2 Glucose polymer (icodextrin) versus standard glucose dialysate, Outcome 5 Change in urine volume (mL).

Change in urine volume (mL)
StudyTime pointGlucose polymerStandard glucose solution
Davies 20031 month-44.3-44.1
Davies 20033 months-34.6-56.6
Davies 20036 months-10.7-126.6
Analysis 2.6.

Comparison 2 Glucose polymer (icodextrin) versus standard glucose dialysate, Outcome 6 Peritoneal creatinine clearance.

Analysis 2.7.

Comparison 2 Glucose polymer (icodextrin) versus standard glucose dialysate, Outcome 7 Episodes of peritonitis.

Analysis 2.8.

Comparison 2 Glucose polymer (icodextrin) versus standard glucose dialysate, Outcome 8 Rash.

Analysis 2.9.

Comparison 2 Glucose polymer (icodextrin) versus standard glucose dialysate, Outcome 9 Technique failure (death-censored).

Analysis 2.10.

Comparison 2 Glucose polymer (icodextrin) versus standard glucose dialysate, Outcome 10 All-cause mortality.

Appendices

Appendix 1. Electronic search strategies

DatabaseSearch terms
CENTRAL
  1. peritoneal dialysis:ti,ab,kw

  2. (CAPD or CCPD or APD or PD):ti,ab,kw

  3. (#1 OR #2)

  4. biocompatib*:ti,ab,kw

  5. bicarbonate*:ti,ab,kw

  6. (lactate* or lactic next acid*):ti,ab,kw

  7. buffer*:ti,ab,kw

  8. (ph next neutral):ti,ab,kw

  9. icodextrin:ti,ab,kw

  10. (((low or lower) near/2 (glucose next degradation next product*)) and (fluid* or solution* or dialysate*)):ti,ab,kw

  11. (((low or lower) near/2 gdp) and (fluid* or solution* or dialysate*)):ti,ab,kw

  12. (#4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11)

  13. (#3 AND #12)

MEDLINE
  1. exp Peritoneal Dialysis/

  2. peritoneal dialysis.tw.

  3. (CAPD or CCPD or APD or PD).tw.

  4. or/1-3

  5. Biocompatible Materials/

  6. Bicarbonates/

  7. Lactates/

  8. Lactic Acid/

  9. Buffers/

  10. biocompatib$.tw.

  11. bicarbonate$.tw.

  12. (lactate$ or lactic acid).tw.

  13. buffer$.tw.

  14. neutral pH.tw.

  15. icodextrin.tw.

  16. (((low or lowering) adj2 glucose degradation product$) and (fluid$ or solution$ or dialysate$)).tw.

  17. (((low or lowering) adj2 GDP) and (fluid$ or solution$ or dialysate$)).tw.

  18. or/5-17

  19. and/4,18

EMBASE
  1. Peritoneal Dialysis/

  2. Continuous Ambulatory Peritoneal Dialysis/

  3. peritoneal dialysis.tw.

  4. (CAPD or CCPD or APD or PD).tw.

  5. or/1-4

  6. Biocompatibility/

  7. Bicarbonate/

  8. Lactic Acid/

  9. Buffer/

  10. biocompatib$.tw.

  11. bicarbonate$.tw.

  12. (lactate$ or lactic acid).tw.

  13. buffer$.tw.

  14. neutral pH.tw.

  15. icodextrin.tw.

  16. (((low or lower) adj2 glucose degradation product$) and (fluid$ or solution$ or dialysate$)).tw.

  17. (((low or lower) adj2 GDP) and (fluid$ or solution$ or dialysate$)).tw.

  18. or/6-17

  19. and/5,18

Appendix 2. Risk of bias assessment tool

Potential source of bias Assessment criteria

Random sequence generation

Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence

Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimization (minimization may be implemented without a random element, and this is considered to be equivalent to being random).
High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.
Unclear: Insufficient information about the sequence generation process to permit judgement.

Allocation concealment

Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment

Low risk of bias: Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study (e.g. central allocation, including telephone, web-based, and pharmacy-controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes).
High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non-opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.
Unclear: Randomisation stated but no information on method used is available.

Blinding of participants and personnel

Performance bias due to knowledge of the allocated interventions by participants and personnel during the study

Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.
High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.
Unclear: Insufficient information to permit judgement

Blinding of outcome assessment

Detection bias due to knowledge of the allocated interventions by outcome assessors.

Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.
High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding.
Unclear: Insufficient information to permit judgement

Incomplete outcome data

Attrition bias due to amount, nature or handling of incomplete outcome data.

Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods.
High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.
Unclear: Insufficient information to permit judgement

Selective reporting

Reporting bias due to selective outcome reporting

Low risk of bias: The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon).
High risk of bias: Not all of the study’s pre-specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. sub scales) that were not pre-specified; one or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study.
Unclear: Insufficient information to permit judgement

Other bias

Bias due to problems not covered elsewhere in the table

Low risk of bias: The study appears to be free of other sources of bias.
High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data-dependent process (including a formal-stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem.
Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias.

What's new

DateEventDescription
18 August 2016AmendedCorrection of table 2 results

History

Protocol first published: Issue 1, 2009
Review first published: Issue 3, 2014

DateEventDescription
2 May 2014AmendedMinor edits to study names to match Renal Group's Specialised Register

Contributions of authors

  • Screening of titles and abstracts: YC, KW

  • Study eligibility: YC, KW

  • Quality assessment, data extraction, data analysis:- KW, YC, GFMS

  • Writing of review: KW, GFMS, DJ, JC, YC, SB

  • Disagreements were resolved in consultation with DJ, SB and JC

Declarations of interest

Professor David Johnson is a consultant for Baxter Healthcare Pty Ltd and has previously received research funds from this company. He has also received speakers Honoria and research grants from Fresenius Medical Care. He has previously been a consultant for Gambro.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Bajo 2011

Methods
  • Study design: parallel RCT

  • Study duration: 4 years

  • Follow-up period: 24 months

Participants
  • Country: Spain

  • Setting: multi-centre (2 centres), university hospital

  • Incident adult CAPD patients

  • Number: treatment group (13); control group (20)

  • Mean age ± SD (years): treatment group (62 ± 11); control group (59 ± 15)

  • Sex (M/F): treatment group (10/3); control group (9/11)

  • Exclusion criteria: none

Interventions

Treatment group

  • Balance (Fresenius Medical Care)

Control group

  • Standard PD fluid (Stay Safe)

Outcomes
  • Peritonitis rate

  • Peritoneal UF (4 hours, 4.25% glucose solution)

  • RRF

  • Patient survival

NotesSupported by grants from RETICS from Instituto de Salud Carlos III and unrestricted grant from Fresenius Medical Care
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskQuote: "patients were alternately assigned to either 'balance' or standard PD fluid depending on the time point of inclusion"
Allocation concealment (selection bias)High riskQuote: "patients were alternately assigned to either 'balance' or standard PD fluid depending on the time point of inclusion"
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskHigh drop-out rate: 21/33 (63.6%)
Selective reporting (reporting bias)Low riskAll relevant outcomes reported
Other biasHigh riskOutcome parameters significantly different at baseline (e.g. urine volume, RRF)

balANZ Trial 2006

Methods
  • Study design: open-label, parallel RCT

  • Study duration: November 2004 to September 2010

  • Follow-up period: 24 months

Participants
  • Countries: Australia, New Zealand, Singapore

  • Setting: multicentre (16 centres)

  • Adult PD patients ≥ 18 and < 81 years (either CAPD or APD); diagnosis of ESKD; first treatment for ESKD by any dialysis modality within 90 days prior to or following enrolment (patients may be enrolled prior to commencing first treatment if there is clear indication that the treatment modality is CAPD or APD and they consent in advance to enter the study); selected to be treated by CAPD or APD; residual GFR at enrolment ≥ 5mL/min/1.73 m²; urine volume/d ≥ 400 mL at enrolment; written informed consent before any study related activities; ability to understand the nature and requirements of the study

  • Number: treatment group (91); control group (91)

  • Mean age ± SD (years): treatment group (59.3 ± 14.2); control group (57.9 ± 14.7)

  • Sex (M/F): treatment group (52/39); control group (48/43)

  • Exclusion criteria: prognosis for survival < 12 months; pregnancy or lactation period; history of malignancy other than a successfully and completely treated cutaneous squamous cell or basal cell carcinoma or carcinoma in-situ of the cervix within the last 5 years; any acute infections at the time of enrolment; any disease of the abdominal wall, such as injury or surgery, burns, hernia, dermatitis, that in the opinion of the Investigator would preclude the patient from being able to have peritoneal dialysis; any inflammatory bowel diseases (Crohn's disease, ulcerative colitis or diverticulitis) that in the opinion of the Investigator would preclude the patient from being able to have peritoneal dialysis; any intra-abdominal tumours or intestinal obstruction; active serositis; any condition (mental or physical) that would interfere with the patient's ability to comply with the study protocol; known or suspected allergy to study product or related products; participation in any other clinical study where an intervention is designed to moderate rate of change of RRF

Interventions

Treatment group

  • Neutral pH, low GDP dialysis solution (Balance)

Control group

  • Conventional dialysis solution (Stay.safe) for a period of 2 years.

Outcomes

Primary outcome

  • Slope of RRF decline measured as GFR (mean of renal urea and CrCl) over time (follow-up 24 months)

Secondary outcomes

  • Time from initiation of PD to anuria (daily urine volume less than 100 mL)

  • Peritoneal small solute clearance (Kt/V, CrCl)

  • Peritoneal transport status (PET D/P creatinine and D/Do glucose)

  • Peritoneal UF capacity (mL/d) and UF (mL/day/m²)

  • Technical survival

  • Patient survival

  • Peritonitis rates

  • Adverse events

NotesStudy funded by Fresenius Medical Care
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "To ensure adequate concealment of allocation, randomization was performed using a central computer and web-based link to the central database, with stratification according to centre and the presence or absence of diabetic nephropathy"
Allocation concealment (selection bias)Low riskQuote: "To ensure adequate concealment of allocation, randomization was performed using a central computer and web-based link to the central database, with stratification according to centre and the presence or absence of diabetic nephropathy"
Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "An open-label study", but unlikely to have influenced the objective outcomes measured
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-out rate 3/185 (1.6%), balanced between groups
Selective reporting (reporting bias)Low riskAll relevant clinical parameters reported
Other biasUnclear riskInsufficient information to permit judgement

Bredie 2001

Methods
  • Study design: cross-over RCT

  • Study duration: not stated

  • Follow-up period: 6 weeks during each arm (overall 3 months)

Participants
  • Country: Netherlands

  • Setting: single centre, university hospital

  • Prevalent adult patients on CAPD; established on CAPD for at least 3 months, using 3-4 standard exchanges/24 hours; free of peritonitis and mechanical drainage complications for at least 3 months prior to their inclusion

  • Number: 21

  • Mean age ± SD: 50.3 ± 11.8 years

  • Sex (M/F):15/6

  • Exclusion criteria: not stated

Interventions

Treatment group

  • 7.5% icodextrin in place of glucose-containing fluid for the overnight dwell

Control group

  • Standard glucose-containing PD fluid (1.36%, 2.27%, 3.86%) for the overnight dwell

Patients performed CAPD with both control and treatment fluids for a period of 6 weeks each

Outcomes
  • Peritonitis

NotesFunding received from Rijnstate Hospital Arnhem and Baxter Healthcare Company, Benelux
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskDrop-out rate: 1/22 (5%)
Selective reporting (reporting bias)High riskLimited clinical outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Cancarini 1998

Methods
  • Study design: parallel RCT

  • Study duration: not stated

  • Follow-up period: 2 months

Participants
  • Country: Italy

  • Setting: multicentre

  • Prevalent adult patients on CAPD

  • Number: treatment group (16); control group (17)

  • Mean age ± SD: 64 ± 11 years

  • Sex (M/F): 15/18

  • Exclusion criteria: not stated

Interventions

Treatment group

  • 33 mmol/L bicarbonate PD solution

Control group

  • Standard 40 mmol/L lactate PD solution

Outcomes
  • Blood pressure

  • Biochemistry - serum bicarbonate, albumin, total protein concentrations

NotesOther clinical parameters (e.g. peritonitis, UF) not reported. However, the primary aim of the study was evaluate the effect on biochemistry. Author contacted, awaiting response
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot stated
Allocation concealment (selection bias)Unclear riskNot stated
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskOpen label, however unlikely to have affected outcome
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
High riskDrop-out rate of 7/33 (21.2%). Reason for dropout not stated
Selective reporting (reporting bias)High riskLimited reporting of outcomes
Other biasUnclear riskInsufficient information to permit judgement

Carrasco 2001

Methods
  • Study design: parallel RCT

  • Study duration:

  • Follow-up period: 3 months

Participants
  • Country: Spain

  • Setting: multicentre

  • Prevalent adult CAPD patients

  • Number: treatment group (20); control group (11)

  • Age, range (years): treatment group (58.8, 23-76); control group (56.7, 34-79)

  • Sex (M/F): treatment group (9/11); control group (5/6)

  • Exclusion criteria: antibiotics during the previous 30 days; serious illnesses (e.g. requiring hospitalisation during the previous 30 days); HIV positive; pregnancy or lactating; bicarbonate supplementation into PD fluids or orally

Interventions

Treatment group

  • 25 mmol/L bicarbonate/15 mmol/L lactate PD solution

Control group

  • Standard 35 mmol/L lactate PD solution

Outcomes
  • Venous plasma bicarbonate concentrations

  • Vital signs

NotesThis was a study primarily examining the ability of the new bicarbonate/lactate PD solutions on improving acidosis in PD patients. Author contacted, awaiting response. Funding received from Baxter Healthcare Ltd
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskBlock randomisation (3 patients/block)
Allocation concealment (selection bias)Unclear riskNot stated
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskOpen label, however, unlikely to have affected measured outcomes
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo drop-out
Selective reporting (reporting bias)High riskLimited reporting of clinical outcomes
Other biasUnclear riskInsufficient information to permit judgement

Choi 2008

Methods
  • Study design: open parallel RCT

  • Study duration: not stated

  • Follow-up period: 12 months

Participants
  • Country: Korea

  • Setting/ study design: single centre, university hospital

  • PrevaIent adult patients on CAPD; maintained on CAPD for at least 6 months prior to study enrolment using standard PDFs, and considered to be adequately dialysed; patients used three or four 1.5 to 2.5 L exchanges/d

  • Number: treatment group (51); control group (53)

  • Mean age ± SD (years): treatment group (52.6 ± 12.4); control group (55.4 ± 11.9)

  • Sex (M/F): treatment group (20/31); control group (27/26)

  • Exclusion criteria: dialysis-related complications (e.g. CAPD peritonitis, exit-site infection, tunnel infection) within the previous 8 weeks; more than 2 episodes of peritonitis within the previous 6 months

Interventions

Treatment group

  • Neutral pH, low GDP solution (Balance; Fresenius Medical Care)

Control group

  • Standard peritoneal dialysis fluid

Outcomes
  • Urine volume

  • All-cause mortality (death due to causes unrelated to PD)

  • 4-hour dialysate:plasma creatinine

  • Change in D:P Cr over the study period

  • Peritoneal UF

  • Change in peritoneal UF

  • Kt/V urea (renal, peritoneal and total)

  • CrCl (renal, peritoneal and total)

NotesFunding received from Yonsei University College of Medicine, the Korean Society of Nephrology and Fresenius Medical Care
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low riskOpen-label design thus no blinding of investigators or participants. However, unlikely to have impacted on objective clinical outcomes (e.g. urine volume)
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskLarge number of patients voluntarily changed to the low GDP PD solution (36/104 (35%)). Per protocol analysis
Selective reporting (reporting bias)Low riskAll appropriate outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Cnossen 2011

Methods
  • Study design: open parallel RCT

  • Study duration: not stated

  • Follow-up period: 3 months

Participants
  • Country: Germany, Netherlands

  • Setting: multicentre (2)

  • PrevaIent adult patients on CAPD

  • Number: treatment group (12); control group (11)

  • Mean age ± SD (years): treatment group (70.0 ± 13.1); control group (55.3 ± 15.6)

  • Sex (M/F): treatment group (9/3); control group (10/1)

  • Exclusion criteria: intercurrent infection; use of 1.1% amino acids (Nutrineal, Baxter Healthcare); treatment with APD

Interventions

Treatment group

  • Neutral pH, low GDP solution (Physioneal; Baxter Healthcare)

Control group

  • Standard peritoneal dialysis fluid (Dianeal, Baxter Healthcare)

Outcomes
  • Advanced glycation end product concentrations

  • RRF

NotesSignificant disparity in baseline age between the two groups noted. Author contacted, awaiting response
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot stated
Allocation concealment (selection bias)Unclear riskNot stated
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot stated
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLow drop-out rate (3/26 (11.5%))
Selective reporting (reporting bias)High riskLimited reporting of clinical outcomes
Other biasHigh riskA large difference in baseline age between the treatment and control groups raise concern for inadequate randomisation

Coles 1997

Methods
  • Study design: parallel RCT

  • Study duration: not stated

  • Follow-up period: 2 months, with optional 4 month extension period

Participants
  • Countries: UK, Italy

  • Setting: multicentre (5)

  • Prevalent adult patients on CAPD for at least 3 months; receiving Dianeal PD4 for at least 1 month; RRF of ≤ 5 mL/min; weekly (renal + peritoneal) CrCl of ≥ 50 L/1.73 m² RRF ≥ 5 mL/min; using 4 or 5, 2 litre bags/24 hours with no dry period

  • Number: treatment group 1 (20); treatment group 2 (20); control group (19)

  • Age, range (years): treatment group 1 (54.5, 21.6 to 73.7); treatment group 2 (54.8, 27.8 to 79.1); control group (58.4, 25.5 to 74.7)

  • Sex (M/F): treatment group 1 (17/3); treatment group 2 (13/7); control group (10/9)

  • Exclusion criteria: low peritoneal transport (4-hour dialysate:plasma creatinine < 0.5); known to be HIV positive; peritonitis within the previous 30 days; suffered from liver disease or diabetes mellitus; added medication routinely to the dialysis bag

Interventions

Treatment group 1

  • Bicarbonate-buffered (38 mmol/L bicarbonate) dialysis fluid

Treatment group 2

  • Bicarbonate/ lactate-buffered (25 mmol/L bicarbonate, 15 mmol/L lactate) dialysis fluid

Control group

  • Conventional lactate-buffered (40 mmol/L lactate) dialysis fluid

Outcomes
  • Peritoneal UF at 2 months

  • Peritonitis

  • Abdominal pain

  • Other adverse events

NotesFunding received from Baxter Healthcare Corporation, Brussels, Belgium
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskBlock randomisation in groups of 3, done separately for each centre; actual method of randomisation not stated
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label. Measured outcome (e.g. abdominal pain) may have been influenced by lack of blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskDrop-out 13/59 (22%). Unequal between three groups with peritonitis being the major cause which may have been due to the treatment received
Selective reporting (reporting bias)Low riskAll relevant clinical outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Davies 2003

Methods
  • Study design: parallel RCT

  • Study duration:

  • Follow-up period: 6 months

Participants
  • Countries: Germany, Sweden, UK

  • Setting: multicentre

  • Prevalent adult patients > 18 years on APD or CAPD; uncontrolled hypertension (BP > 140/90 mmHg), treated hypertension, or a dialysis prescription with a daily average glucose concentration of ≥ 2.27%; high or high-average peritoneal solute transport (corrected 4h D/P creatinine ratio ≥ 0.65); urine output ≤ 750 mL/d; patient tolerance of a dialysis regimen with a long dwell of ≥ 6 hours with 2.27% glucose with fill volume of 1.5 to 2.5 L; able to give written informed consent; on PD for at least 90 days

  • Number: treatment group (28); control group (22)

  • Mean age ± SD (years): treatment group (56 ± 15); control group (54 ± 15)

  • Sex (males): treatment group (54%); control group (45%)

  • Exclusion criteria: received icodextrin or other non-glucose solutions in the 30 days before randomisation; treated for peritonitis in the 30 days before randomisation; considered noncompliant; considered to have hypertension despite being clinically volume depleted; use of a 1.36% glucose solution for each exchange; allergy to starch; glycogen storage disease; life expectancy < 12 months; serious illness or injury in the 30 days before randomisation that would invalidate study entry; participation in another interventional study; pregnant or lactating; significant psychiatric disorder that would interfere with their ability to provide informed consent and/ or comply with the study procedures

Interventions

Treatment group

  • 7.5% icodextrin for the long dwell

Control group

  • 2.27% glucose (Dianeal) for the long dwell

Outcomes
  • Decline in RRF (change in urine output)

  • Change in peritoneal UF volume

NotesFunded by Baxter Healthcare
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote from Methods section of paper: "Randomised 1:1 with stratification for centre/country, dialysis modality (CAPD or APD), and presence of cardiovascular disease or LVH"
Allocation concealment (selection bias)Low riskQuote from Methods section of paper: "The treatment codes were supplied to study sites in sealed envelopes, which were checked at the end of the study"
Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote from Methods section of paper: "Identity of the long-dwell solution blinded to patients, investigators and clinical monitors; specially created packaging was used to conceal which solution was which solution was which"
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High risk

Drop-out rate 20% (10/50)

Quote from Results section of paper: "Additional withdrawals from the 2.27% glucose group were for UF failure and patient preference"

Selective reporting (reporting bias)Low riskAll relevant outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

di Paolo 2000

Methods
  • Study design: cross-over RCT

  • Study duration: not stated

  • Follow-up period: 3 months

Participants
  • Country: Italy

  • Setting: single centre

  • CAPD patients with clinical signs such as hypotension and hyperhydration

  • Number: 9

  • Mean age (range): 72.5 years (50 to 83)

  • Sex (M/F): 6/3

  • Exclusion criteria: not stated

Interventions
  • Night dwell (> 6 hours) of icodextrin

Cross-over design, with two study periods of 3 months each, separated by a 2 week wash out period

Outcomes
  • Arterial blood pressure

NotesThe study was reported in abstract form only, with blood pressure the only clinical endpoint reported. Data from the first arm of the cross-over study was unable to be isolated. Attempts to contact the authors for further information were unsuccessful due to inability to find contact details
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information provided
Selective reporting (reporting bias)Unclear riskNo information provided
Other biasUnclear riskNo information provided

DIUREST Study 2010

Methods
  • Study design: open, parallel RCT

  • Study duration: 1999 to 2005

  • Follow-up period: 18 months

Participants
  • Country: Germany, France, Austria

  • Setting: multicentre (23)

  • Adult patients on CAPD or APD, 18-80 years; ESKD, GFR ≥ 3 mL/min (arithmetic mean of renal urea and CrCl) or ≥ 6 mL/min (CrCl) as measured by 24-hour urine collection

  • Number: treatment group (44); control group (36)

  • Mean age ± SD (years): treatment group (52 ± 12); control group (53.8 ± 14.6)

  • Sex (M/F): treatment group (36/18); control group (14/12)

  • Exclusion criteria: pregnant or breastfeeding; severe peritonitis episodes; cancer; positive for hepatitis B, hepatitis C and HIV

Interventions

Treatment group

  • Received either Gambosol trio, a multi-compartment bag with minimal amounts of GDPs (3, 4-DGE < 1 µM)

Control group

  • Standard PD fluids from different manufacturers in single compartment bags, all containing 3,4-DGE (13-20 µM)

Outcomes
  • RRF (arithmetic mean of renal creatinine and urea clearance)

  • Assessment of fluid balance (body weight, 24-hour urine volume)

  • Serum parameters (CRP, total protein, albumin, electrolytes and phosphate)

  • CA125 in PD effluent

  • Assessment of peritoneal membrane transport characteristics

  • Medications (e.g. blood pressure medications, diuretics and phosphate binders)

NotesSponsored by Gambro
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote from Methods section of paper: "Randomization was performed by means of a centrally managed list based on a table of random numbers in blocks of four and stratified for the presence of diabetes"
Allocation concealment (selection bias)Low riskQuote from Methods section of paper: "Randomization was performed by means of a centrally managed list based on a table of random numbers in blocks of four and stratified for the presence of diabetes"
Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote from Methods section of paper: "... open, parallel study". As fluid balance is one of the main outcomes assessed, risks influencing co-intervention
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskHigh drop-out rate (41/80 (51.3%)), imbalance between the number of dropouts from each arm. Per protocol analysis
Selective reporting (reporting bias)Low riskAll relevant clinical outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

EURO-BALANCE Study 2004

Methods
  • Study design: open, cross-over design and parallel arms

  • Study duration: not stated

  • Follow-up: 12 weeks

Participants
  • Country: 11 European countries

  • Setting: multicentre (22)

  • Prevalent adult patients on PD

  • Number: treatment group (36); control group (35)

  • Median age, IQR (years): treatment group (61, 46-68); control group (57, 51-71)

  • Sex (M/F): treatment group (19/7); control group (23/12)

  • Exclusion criteria: not stated

Interventions

Treatment group

  • neutral pH, low GDP dialysate (Balance)

Control group

  • Conventional dialysate

Patients received 12 weeks of treatment with both solutions

Outcomes
  • 4-four dialysate:plasma creatinine

  • Kt/V

  • CrCl

  • UF

  • Urine volume

  • Peritonitis rate

  • Adverse events (including inflow pain)

NotesStudy funded by Fresenius Medical Care
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Specific randomisation technique not stated.

Quote: "After the run-in phase, patients were randomized (1:1) to either ..."

Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen-label study with subjective outcome measure such as inflow pain was one of the assessed parameters
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskDropout rate: 15/86 (17%). Although per protocol analysis performed, the reasons for dropout from initial study group is balanced after excluding the reasons that are unlikely to be dialysis related (e.g. transplantation, flare-up of vasculitis)
Selective reporting (reporting bias)Low riskAll relevant outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Fan 2008

Methods
  • Study design: parallel RCT

  • Study duration: 1 January 2004 to 31 December 2005

  • Follow-up: 12 months

Participants
  • Country: UK

  • Setting: single centre

  • Incident adult patients on APD or CAPD

  • Number: treatment group (57); control group (61)

  • Mean age ± SD (years): treatment group (51.6 ± 2); control group (54.5 ± 1.7)

  • Sex (M/F): treatment group (38/19); control group (39/22)

  • Exclusion criteria: not stated

Interventions

Treatment group

  • Biocompatible solution (Physioneal or Balance depending on the connectology that was felt to be best suited to the individual)

Control group

  • Standard PD solution (Dianeal or Stay Safe depending on the connectology that was felt to be best suited to the individual)

Outcomes
  • RRF (assessed by 24-h urine collection)

  • Peritonitis rate

  • PD technique survival

  • Changes in peritoneal membrane function using PET

  • Biomarker of inflammation, CRP

Notes

Differences in connectology may have influenced the peritonitis risk.

Baxter group also allowed to use Nutrineal/Icodextrin

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low riskNo blinding of investigators or participants. However, unlikely to have impacted on objective clinical outcomes (e.g. urine volume)
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskdropout rate of 21.2% (25/118). Not all accounted for with many under "did not complete". Reason unclear
Selective reporting (reporting bias)Low riskAll relevant outcomes reported
Other biasHigh risk

Issue of connectology and allowance of Nutrineal/icodextrin usage in patients who used Baxter System.

Multiple types of PD solutions used in both intervention and control groups

Feriani 1998

Methods
  • Study design: parallel, open label RCT

  • Study duration: not stated

  • Follow-up period: 24 weeks

Participants
  • Countries: Germany

  • Setting: multicentre (14)

  • Adult patients on CAPD (prevalent) who were free of peritonitis for at least 4 weeks preceding the study commencement.

  • Phase II study (24 weeks)

    • Number: treatment group (37); control group (36)

    • Median age, range (years): treatment group (54.5, 18.6-78); control group (55, 21.27-79.4)

    • Sex (M/F): treatment group (17/20); control group (20/16)

  • Exclusion criteria: not stated

Interventions

Treatment group

  • 34 mmol/L bicarbonate-buffered solution

Control group

  • 35 mmol/L lactate-buffered peritoneal dialysis solution

Outcomes
  • RRF

  • UF

  • Subjective assessment - symptoms

  • Adverse events

Notes

Grant from Fresenius.

Phase I study data only available from conference abstract

36 patients left at the end of phase I of study - no explanation provided.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomised centrally and separately for each study centre and block randomisation in steps of four used
Allocation concealment (selection bias)Low riskNo specific information provided. However central randomisation with probable low risk of selection bias
Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label, may have affected symptom assessment
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskLarge number of participants missing between two phases of study that are not accounted for in the paper. 18/123 (14.6%) for 12 weeks; 4/73 (5.5%) for 24 week study
Selective reporting (reporting bias)Low riskAll relevant clinical outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Fernandez-Perpen 2012

Methods
  • Study design: prospective RCT, presumed open-label (not disclosed)

  • Study duration: not stated

  • Follow-up period: 24 months

Participants
  • Countries: Spain

  • Setting: multicentre (2 university hospitals)

  • Incident patients who are able and willing to perform CAPD with no expressed indication for APD

  • Number: treatment group (11); control group (20)

  • Mean age ± SD (years): treatment group (68.22 ± 8.8); control group (59 ± 15)

  • Sex (M/F): treatment group (8/3); control group (9/11)

  • Diabetic: treatment group (38%); control group (15%)

  • Exclusion criteria: none

Interventions

Treatment group

  • BicaVera (1.5, 2.3%, 4.25% glucose)

Control group

  • Conventional PD fluid (Stay-safe; 1.5%, 2.3% and 4.25%)

Outcomes
  • Peritonitis rate

  • Death

  • Technique survival

  • UF capacity

  • RRF

Notes

Study supported by grants from REDinREN, MLC and unrestricted grant from Fresenius Medical Care.

Note - significant difference in outcome re: UF capacity and RRF reported, but these differences were present from the baseline

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskQuote: "patients were randomly assigned to either BicaVera or the standard PD fluid by the doctors"
Allocation concealment (selection bias)High riskQuote: "patients were randomly assigned to either BicaVera or the standard PD fluid by the doctors"
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskHigh dropout rate (23 /31 (74.2%)). Imbalance in missing data between the two groups
Selective reporting (reporting bias)Low riskAll relevant clinical outcomes reported
Other biasHigh riskOutcome parameters significantly different at baseline (e.g. urine volume, RRF)

Finkelstein 2005

Methods
  • Study design: parallel RCT

  • Study duration: 1 July 2001 to 11 October 2003

  • Follow-up period: 2 weeks

Participants
  • Countries: Australia, USA

  • Setting: multicentre

  • Adult patients ≥ 18 years on APD with peritoneal membrane transport characteristics in the high-average or high category; high or high average peritoneal transport characteristics (4-hour dialysate:plasma creatinine > 0.70 and 4-hour D/D₀ glucose < 0.34) based on the results of the screening PET; receiving treatment with APD using HomeChoice (Baxter) or HomeChoice PRO (Baxter) cycler for at least 30 days before the baseline visit; stable on their PD prescription before the screening visit; using an APD prescription for at least 3 days before the baseline visit that included a long-dwell exchange with duration of 12 to 16 hours and fill volume of 2.0 to 2.5 L of a 4.25% dextrose solution; stable health; able to tolerate a 12 to 16 hour long dwell; free from peritonitis for at least 45 days before use of the study solution

  • Number: treatment group (47); control group (45)

  • Mean age ± SD (years): treatment group (50.1 ± 2.1); control group (53.3 ± 1.8)

  • Sex (M/F): treatment group (28/19); control group (28/17)

  • Exclusion criteria

Interventions

Treatment group

  • 7.5% icodextrin (Extraneal; Baxter) for the long dwell

Control group

  • 4.25% dextrose solution (Dianeal PD-2; Baxter) for the long dwell

Outcomes
  • UF

  • Small solute clearances

  • Adverse events (rash)

NotesStudy funded by Baxter Healthcare Corporation, which also manufactured the double-blind product
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskCentrally maintained randomisation list
Allocation concealment (selection bias)Low riskCentrally maintained randomisation list
Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blind - use of identical solution bags
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskDropout rate: 7/92 (8%), balanced between groups
Selective reporting (reporting bias)Unclear riskAll relevant outcomes within the short time frame reported
Other biasUnclear riskInsufficient information to permit judgement

Fusshoeller 2004

Methods
  • Study design: open, cross-over RCT

  • Study duration: not stated

  • Follow-up period: 12 months (6 months in each phase)

Participants
  • Country: Germany

  • Setting: single centre, university

  • Adult patients on APD

  • Number: 14

  • Mean age ± SD: 40.0 ± 10.7 years

  • Sex (M/F): 4/10

  • Exclusion criteria: not stated

Interventions

Treatment group

  • Neutral pH bicarbonate/ lactate buffered PD solution (Physioneal; Baxter Healthcare)

Control group

  • Conventional PD solution (Dianeal; Baxter Healthcare)

Patients completed 6 months of APD using either control or treatment PD solution, followed by a further 6 months of APD using the alternative PD solution

Outcomes
  • Inflow pain

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskNot blinded. This is particularly relevant as 'inflow pain' was reported as one of the outcomes in unblinded state
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported
Incomplete outcome data (attrition bias)
All outcomes
Low riskDropout rate: 2/14 (14%)
Selective reporting (reporting bias)High riskPrimary outcome of interest of this study related to peritoneal macrophages and inflammatory markers. No other clinical parameter was reported - including peritonitis, survival, RRF
Other biasUnclear riskInsufficient information to permit judgement

Kim 2003

Methods
  • Study design: parallel RCT

  • Study duration: not stated

  • Follow-up period: 12 months

Participants
  • Country: South Korea

  • Setting: multicentre (2 hospitals)

  • Incident adult patients on CAPD

  • Number: treatment group (16); control group (10)

  • Mean age ± SD (years): treatment group (51.6 ± 3.6); control group (56.1 ± 5.2)

  • Sex (M/F): not stated

  • Exclusion criteria: not stated

Interventions

Treatment group

  • Low GDP PD solution (pH 7.0, two compartment bag, Staysafe Balance solution; Fresenius Medical Care)

Control group

  • Standard glucose-containing dialysis fluid (pH 5.5, single compartment bag, stay-safe; Fresenius Medical Care)

Outcomes
  • RRF

  • Peritoneal transport (4-hour dialysate:plasma creatinine)

NotesFunding received from Fresenius Medical Care Korea and Medical Research Institute grant, Kyungpook National University Hospital (1998)
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided, stratified for diabetes mellitus
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low riskOpen-label, however unlikely to have influenced the objective outcome measured
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskDropout rates - 38/64 (59%). Missing participants not accounted for. Per protocol analysis
Selective reporting (reporting bias)High riskNo report of peritonitis or survival
Other biasUnclear riskInsufficient information to permit judgement

Kim 2008

Methods
  • Study design: open-label, parallel RCT

  • Study recruitment period: June 2004 to May 2006

  • Follow-up period: 12 months (24-month follow-up result in abstract form available)

Participants
  • Country: South Korea

  • Setting: multicentre

  • Incident adult patients > 18 years commencing on CAPD

  • Number: treatment group (48); control group (43)

  • Mean age ± SD (years): treatment group (55.3 ± 13.2); control group (52.8 ± 13.6)

  • Sex (M/F): treatment group (31/17); control group (24/19)

  • Exclusion criteria: mechanical problems with PD catheter; expected kidney transplantation within 12 months; life expectancy < 6 months; plans to transfer to another hospital; dialysis required due to acute renal failure; patient refusal

Interventions

Treatment group

  • Low-GDP solution (Balance)

Control group

  • Conventional PD solution

After 4-week run-in phase on conventional fluid, each group started CAPD with the designated PD solution

Outcomes

Primary end point

  • GFR defined by the mean of renal urea and CrCl

Secondary end points

  • Urine volume

  • Survival: patient survival, technique survival and peritonitis-free survival

  • Clinical laboratory data: peritoneal solute transport rate represented by dialysate-to-plasma ratio for creatinine at 4h (D/P Cr) and blood chemistry

NotesPartly supported by Fresenius Korea
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Quote: "open-labelled, randomised, prospective study"

However, unlikely to have influenced the objective outcomes measured

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskDropout rate, 22/91 (24.1%), 5/48 patients in low GDP group switched to haemodialysis - no reason specified that may have been relevant to the therapy they had received
Selective reporting (reporting bias)Low riskAll relevant clinical outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Konings 2003

Methods
  • Study design: parallel RCT

  • Study duration:

  • Follow-up period: 4 months

Participants
  • Country: The Netherlands

  • Setting: multicentre

  • Prevalent adult patients on CAPD and APD

  • Number: treatment group (22); control group (18)

  • Mean age ± SD (years): treatment group (52.7 ± 10.9); control group (56.4 ± 11.6)

  • Sex (M/F): treatment group (14/8); control group (14/8)

  • Exclusion criteria: recent complications (e.g. peritonitis, malignancy, surgery); type I diabetes mellitus; congestive heart failure or coronary artery disease (defined as NYHA class III and higher)

Interventions

Treatment group

  • 7.5% icodextrin in place of glucose-containing fluid for the overnight dwell (patients on CAPD) or the daytime dwell (patients on APD)

Control group

  • Standard glucose-containing peritoneal dialysis fluid

Outcomes
  • Technique failure

  • Peritonitis

  • Other adverse events (exfoliative dermatitis)

  • Peritoneal UF

  • Residual renal GFR

  • Urine output

Notes

Funding received from Baxter Healthcare

Performed baseline characteristics as if ITT but performed as per protocol for the outcome assessment

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot stated
Allocation concealment (selection bias)Low risk"Randomized with the use of sealed envelopes"
Blinding of participants and personnel (performance bias)
All outcomes
Low riskOpen label - but unlikely to have influenced objective outcomes measured
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskDropout 20% (8/40), but all accounted for. Per protocol analysis
Selective reporting (reporting bias)Low riskAll relevant clinical outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Lai 2012a

Methods
  • Study design: parallel RCT

  • Study duration: commenced July 2003

  • Follow-up period: average 3.6 years

Participants
  • Country: Hong Kong

  • Setting: multicentre

  • Incident adult patients on CAPD

  • Number: treatment group (58); control group (67)

  • Mean age ± SD (years): treatment group (56.4 ± 1.6); control group (59.5 ± 1.35)

  • Sex (M/F): treatment group (36/22); control group (33/34)

  • Exclusion criteria: malignancy; systemic lupus erythematosus; chronic valvular or congenital heart disease

Interventions

Treatment group

  • low-GDP PDFs, Gambrosol Trio, Physioneal 40 and Balance

Control group

  • Conventional PD Solutions - lactate-buffered glucose based Dianeal PD-2 or ANDY-Disc

Outcomes

Composite co-primary outcomes

  • biochemical profile of cytokines, growth factors, adipokines, and cardiac biomarkers determined after stable PD treatment for an average duration of 2.3 years

  • dialysis adequacy determined by GFR and daily urine output at initiation and at the time of census after stable PD for an average duration of 3.6 years

Also determined

  • UF

  • Urine volume

  • Dialysis Adequacy (Kt/V, CrCl)

  • Residual GFR

  • 4-hour dialysate:plasma creatinine

Notes

Study supported in part by a Renal Discoveries-International Society of Nephrology grant and a Baxter extramural grant

Randomisation and recruitment into this study unusual. Patients were informed only at 2.3 years after starting their 'study' of their participation

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskRandom assignments were made by the patient's training nursing officer at the individual renal centre
Allocation concealment (selection bias)High riskRandom assignments were made by the patient's training nursing officer at the individual renal centre
Blinding of participants and personnel (performance bias)
All outcomes
Low riskOpen-label, however unlikely to have affected the objective outcomes measured
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskPer protocol analysis
Selective reporting (reporting bias)High riskPeritonitis not reported
Other biasHigh risk

Although baseline characteristics were reported to be similar. The paper did not disclose the duration of PD that these patients received, so one cannot exclude that they may represent different vintage.

Also, for biochemical analyses, there is no baseline value available, thus it is difficult to be certain whether differences are present truly or due to type I error

Multiple types of PD solutions used in intervention and control groups.

Lin 2009a

Methods
  • Study design: parallel RCT

  • Study duration: not stated

  • Follow-up period: 4 weeks

Participants
  • Country: China

  • Setting: multicentre (7)

  • Prevalent CAPD patients ≥ 18 years stable during at least 90 days; a minimum of 6 L of daily 2.5% Dianeal PD-2 or PD-4 dialysate with a night dwell above 8 hours; night dwell volume of 2 L for a minimum of 30 days before inclusion

  • Number: treatment group (98); control group (103)

  • Mean age ± SD (years): treatment group (56.8 ± 13.5); control group (55.4 ± 14.0)

  • Sex (M/F): treatment group (51/47); control group (45/58)

  • Exclusion criteria: Documented anaphylaxis with icodextrin; concomitant chronic diseases such as hepatitis, malignancy, severe cardiac disease; ongoing infection or known infection within the last 30 days; planned or ongoing pregnancy; participation in another clinical or drug study concurrently

Interventions

Treatment group

  • 7.5% icodextrin in night dwell

Control group

  • 2.5% glucose (Dianeal) in night dwell

Outcomes
  • Changes of peritoneal CrCl (mL/min)

  • Changes of UF volume

  • Metabolic parameters (fasting blood glucose, cholesterol, and triglycerides)

NotesAdditional information obtained from author
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "Randomization was done using a computer program that generated numbers instead of treatment assignments"; block randomisation, using a 1:1 ratio
Allocation concealment (selection bias)Low riskQuote: "Envelopes that contained the number corresponding to the dialysate regiment were held by personnel not directly involved with the study, and could be opened only in an emergency"
Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Neither doctors nor patients knew the dialysate regimen"
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Neither doctors nor patients knew the dialysate regimen"
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskLow Dropout rate, 18/201 (8.9%)
Selective reporting (reporting bias)Low riskAll relevant clinical outcome parameters are reported
Other biasUnclear riskInsufficient information to permit judgement

Mactier 1998

Methods
  • Study design: cross-over RCT

  • Study duration: not stated

  • Follow-up period: three study visits within 1-3 week period

Participants
  • Countries: UK, Sweden

  • Setting: multicentre (8)

  • Prevalent adult patients on CAPD ≥ 18 years and experienced repeated infusion pain that based on medical judgement was not related to the catheter or excessive intraperitoneal volume of dialysis fluid

  • Number: 18

  • Mean age: 63.5 years

  • Sex (M/F): not stated

  • Exclusion criteria: peritonitis within the previous 30 days

Interventions

Patients evaluated during two dialysis exchanges with each test solution in random order. Thus, all patients underwent six separate study dwells, with a maximum of 2 test evaluations in 1 day, but it was required that these study exchanges were separated by a routine dwell (40 mM lactate solution) of at least 4 hours. All dwells for at least 3 hours, using 3.86% glucose solutions. Solutions used:

  1. Lactate - Dianeal PD4

  2. Bicarbonate

  3. Bicarbonate/lactate

Outcomes
  • Pain scores

  • Adverse symptoms

NotesLarge variation within the 8 participating centres in the frequency of inflow pain. Mean frequency was 1/25 (range 1/3 to 1/66) patients
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blind
Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble-blind
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk1/18 (5.6%) lost to follow-up
Selective reporting (reporting bias)Unclear riskLimited reporting of outcomes, but given short duration of study, not possible
Other biasHigh riskLarge variation within the 8 participating centres in the frequency of inflow pain

MIDAS Study

Methods
  • Study design: parallel RCT

  • Study duration: March 1991 to February 1992

  • Follow-up period: 6 months

Participants
  • Country: UK

  • Setting: multicentre (11)

  • Prevalent adult patients on CAPD ≥ 18 years or older and established on CAPD for at least 3 months using standard 3 to 4 exchanges, with no more than one hypertonic (3.86% glucose) bag/24 hours; free of peritonitis and mechanical drainage complications for at least one month prior to the study

  • Number: treatment group (103); control group (106)

  • Mean age ± SD (years): treatment group (55 ± 15); control group (55 ± 14)

  • Sex (M/F): treatment group (67/36); control group (71/35)

  • Exclusion criteria: not stated

Interventions

Treatment group

  • 7.5% icodextrin as overnight dwell

Control group

  • Standard glucose-containing peritoneal dialysis fluid as overnight dwell

Outcomes
  • All-cause mortality

  • Peritonitis rate

  • Peritoneal UF

NotesStudy supported by ML Laboratories plc and conducted by Innovata Biomed Limited
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "telephone from a single office (Innovata Biomed) at the first visit"
Allocation concealment (selection bias)Low riskQuote: "telephone from a single office (Innovata Biomed) at the first visit"
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskAlthough mod-high dropout rate (71/209 (34%)), all missing participants are accounted for and reasonably balanced in terms of cause
Selective reporting (reporting bias)High riskRRF not reported
Other biasUnclear riskInsufficient information to permit judgement

Pajek 2008

Methods
  • Study design: open label, cross-over RCT

  • Study duration: not stated

  • Follow-up period: 6 months

Participants
  • Country: Slovenia

  • Setting: single-centre, University hospital

  • Prevalent CAPD patients (adult), treated with Dianeal solution for at least 3 months and > 18 years

  • Number: 21

  • Mean age ± SD: 54.3 ± 12.4 years

  • Sex (M/F): 13/8

  • Exclusion criteria: peritonitis episode in the last 3 months; a history of or current systemic inflammatory disease or immunomodulatory therapy; HIV, HBV or HCV positivity or other chronic infectious disease; malignant disease; acute exacerbation of heart failure in the last 3 months prior to inclusion in the study

Interventions
  • After 1-month run-in phase with the Dianeal solution (D solution), patients were randomised (1:1) to either 3 months of treatment with the D solution (group D-P) or to 3 months of treatment with Physioneal 40 (P solution; group P-D)

  • After 3 months, patients switched therapies to receive a further 3 months of treatment

Outcomes

Primary endpoint

  • Daily UF

Secondary endpoints

  • Overnight UF of a timed 10-hour dwell

  • 4-hour UF with 2.27% solution on PET

  • Low-molecular-weight solute peritoneal transport rates expressed as a D/P for creatinine ratio and D/D1 for glucose ratio

  • Peritoneal urea and CrCl

  • Residual GFR

NotesStudy partly supported by a grant from the Slovenian Research Agency and partly by a grant from Baxter Healthcare, Ljubljana, Slovenia. One of the authors is employed by Baxter Healthcare
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot reported other than, quote: "patients were randomized (1:1)"
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "open-label, randomized". However, unlikely to have influenced the measured objective outcomes
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskDropout rate - 5/26 (19.2%). Per protocol analysis
Selective reporting (reporting bias)Low riskAll relevant outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Paniagua 2008

Methods
  • Study design: open label, parallel RCT

  • Study recruitment: October 2004 to January 2005

  • Follow-up period: 12 months

Participants
  • Country: Mexico

  • Setting: multicentre (4 centres)

  • Adult prevalent CAPD patients; diabetes mellitus; high and high average peritoneal transport status

  • Number: treatment group (30); control group (29)

  • Mean age ± SD (years): treatment group (58.9 ± 7.9); control group (60.5 ± 9.3)

  • Sex (M/F): treatment group (12/18); control group (16/13)

  • Exclusion criteria: seropositive for hepatitis B or HIV; malignancies; receiving immunosuppressive medications; peritonitis episode within 1 month of screening period

Interventions

Treatment group

  • 7.5% icodextrin in the long dwell

Control group

  • At least 1 bag with 2.5% glucose in the long dwell

Liberal use of 2.5% or 4.25% glucose was allowed in both groups in order to reach treatment goals.

Dietary sodium intake prescription was 50 mmol/d for both groups

Outcomes

Primary outcomes

  • Improvement in peritoneal UF

  • Reduction in extracellular fluid volume

  • Improvement in metabolic control

Secondary outcomes

  • Hospitalisations

  • Therapy-related complications

NotesFinancial support from Baxter, SA de RL, Mexico
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: Assignment was in a 1:1 ratio through a central randomization centre
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low riskOpen-label study. However, unlikely to have influenced the objective outcomes measured
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High risk23 participants dropped out. It is also unclear if 23 were out of 59, or the 82 participants to start with. Per protocol analysis
Selective reporting (reporting bias)High riskLimited reporting of clinical outcomes
Other biasUnclear riskInsufficient information to permit judgement

Plum 2002

Methods
  • Study design: open label, parallel RCT

  • Study duration: January 1997 to February 1998

  • Follow-up period: 14 weeks

Participants
  • Countries: Germany, France; Belgium

  • Setting: multicentre

  • Adult prevalent APD patients who had been treated with APD for at least 90 days before the screening visit and whose standard prescription included a long dwell daytime exchange of 2L of 2.27% glucose PD4. Excluded patients with any dry period.

  • Number: treatment group (20); control group (19)

  • Mean age, range (years): treatment group (46.1, 27 to 74); control group (45.5, 26 to 75)

  • Sex (M/F): treatment group (13/6); control group (17/3)

  • Exclusion criteria: not stated

Interventions

Treatment group

  • 7.5% icodextrin as daytime dwell

Control group

  • Daytime dwell of Dianeal 2.27%

Outcomes
  • Solute transport - peritoneal urea and CrCl, RRF

  • Fluid balance - net UF, blood pressure, body weight

  • Adverse events

Notes

Two diabetic patients in each group

Funded by Baxter

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen-label, could have affected introduction of co-intervention affecting the fluid balance measurement
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskPer protocol analysis; 6/39 (15.4%) lost to follow-up
Selective reporting (reporting bias)High riskPeritonitis not reported
Other biasUnclear riskInsufficient information to permit judgement

Posthuma 1997

Methods
  • Study design: open label, parallel RCT

  • Study duration:

  • Follow-up period: 24 months

  • Loss to follow-up: 13/38 (34%) at 24 months

Participants
  • Country: Netherlands

  • Setting: single centre

  • Adult prevalent (and some presumed incident) CCPD patients

  • Number: treatment group (19); control group (19)

  • Mean age, range (years): treatment group (49, 32 to 71); control group (56, 21 to 68)

  • Sex (M/F): not stated

  • Exclusion criteria: women of childbearing potential were excluded unless taking adequate contraceptive precautions

Interventions

Treatment group

  • icodextrin for the daytime dwell (14 to 16 hours)

Control group

  • glucose-containing solution as daytime dwell

Outcomes
  • Death

  • Peritonitis

  • Body weight

  • RRF

  • UF

  • Urine volume

  • Serum creatinine

  • CrCl

  • Weight

Notes

Partially supported by ML laboratories

There are 13 publications associated with this study

Due to variable follow-up, number of assessed patients in publications differ

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low riskOpen label, unlikely to have influenced the objective outcomes measured
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskDropout rate of 34% (13/38), but all accounted for and balanced
Selective reporting (reporting bias)Low riskAll relevant outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Rippe 2001

Methods
  • Study design: open label, parallel RCT

  • Study duration: not stated

  • Follow-up period: 24 months (initially planned for 12 month study, extended to 24 months without additional patient recruitment)

Participants
  • Country: Denmark, Sweden

  • Setting: multicentre (5 centres)

  • Adult incident and prevalent CAPD patients, > 18 years, able to use 2L bags with a calcium concentration of 1.35 mmol/L

  • Number: treatment group (40); control group (40)

  • Mean age, range (years): treatment group (58, 28 to 80); control group (57, 26 to 82)

  • Sex (M/F): treatment group (25/15); control group (30/10)

  • Exclusion criteria: seropositive for hepatitis B or HIV; malignancy; pregnant

Interventions

Treatment group

  • neutral pH, low GDP PD solution

Control group

  • Gambrosol 40 CAPD solution

Outcomes
  • Personal dialysis capacity (PDP) used as a tool to:

    • Assess peritoneal transport characteristics

    • Evaluate RRF

  • UF following overnight dwell using 2.5%

  • Dialysate markers - e.g. CA125, hyaluronan, PICP, PIINP

  • Infusion pain

Notes

Supported by Gambro

Pain assessment not blinded

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskCentral randomisation office (stratified randomisation with respect to patient age (< 55, > 55 years), diabetes (using insulin or not), and time on PD (< 9 months, > 9 months))
Allocation concealment (selection bias)Low riskNot reported but presume low risk given central randomisation
Blinding of participants and personnel (performance bias)
All outcomes
High risk"Open-label". During pain assessment phase, no blinding took place which may have affected patient response
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskAlthough all dropouts accounted for, extremely high proportion (67/80, 83.75%) did not complete the study duration
Selective reporting (reporting bias)High riskRRF not reported
Other biasUnclear riskInsufficient information to permit judgement

Schmitt 2002

Methods
  • Study design: open cross-over RCT

  • Study duration: not stated

  • Follow-up period: 12 weeks

Participants
  • Countries: Austria, France, Germany

  • Setting: multicentre (6 specialised paediatric dialysis units)

  • Prevalent paediatric patients < 18 years on APD with an average peritoneal fill volume close to 1000-1100 mL/m² BSA

  • Number: 28

  • Median age (range): 6.0 years (range 0.6 to 15.7)

  • Sex (M/F): 19/9

  • Exclusion criteria: severe chronic pulmonary, cardiac, hepatic or malignant disease; history of peritonitis in the previous 3 weeks; clinical evidence of major peritoneal adhesions

Interventions

Treatment group

  • Neutral pH PD fluid (34 mM bicarbonate, BicaVera 170/180/190; Fresenius Medical Care)

Control group

  • Conventional PD fluid (35 mL lactate, pH 5.5, CAPD 17/18/19; Fresenius Medical Care)

Patients performed their usual APD regimen with either the control or treatment fluid for 12 weeks. After a 4 week washout period they completed 12 weeks of APD using the alternative fluid

Outcomes
  • Peritonitis rate, relapsing peritonitis rate

  • Other adverse events (acute fluid overload, aggravated hypertension, severe hyperparathyroidism)

  • Residual GFR

  • 24-hour UF

  • Peritoneal transport (4-hour dialysate:plasma creatinine)

NotesFunding received from Fresenius Medical Care (Bad Homburg, Germany)
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low riskOpen-label, however, unlikely to have influenced the objective outcome measures reported
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskHigh dropout rate (12/28, 43%), unclear during which phase of treatment the dropouts occurred. Per protocol analysis
Selective reporting (reporting bias)Low riskAll relevant clinical outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Szeto 2007

Methods
  • Study design: parallel RCT

  • Study duration

  • Follow-up: 12 months

  • Loss to follow-up: 2/50 (4%)

Participants
  • Country: Hong Kong

  • Setting: university teaching hospital

  • Incident adult patients on CAPD

  • Number: treatment group (25); control group (25)

  • Mean age ± SD (years): treatment group (60.9 ± 11.2); control group (55.0 ± 13.7)

  • Sex (M/F): treatment group (16/9); control group (14/11)

  • Exclusion criteria: unlikely to survive; planned to have elective living-related kidney transplant or transfer to other renal centre within 6 months

Interventions

Treatment group

  • Neutral pH (lactate buffered), low GDP dialysate (Balance; Fresenius)

Control group

  • Conventional dialysate

Outcomes
  • Total Kt/V

  • Residual GFR

  • UF

  • Urine output

  • Length of hospitalisation

  • Technique failure

  • All-cause mortality

NotesStudy partially funded by Fresenius Medical Care
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "randomized by drawing sealed envelopes, which were prepared and then maintained by a third party not involved in the conduction of the study"
Allocation concealment (selection bias)Low riskQuote: "randomized by drawing sealed envelopes, which were prepared and then maintained by a third party not involved in the conduction of the study"
Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Open-label", but unlikely to have influenced the objective outcomes measured
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported other than for Subjective global assessment - trained observers were blinded from treatment group allocation and biochemical results of the patients
Incomplete outcome data (attrition bias)
All outcomes
Low riskDropout rate: 2/50 (4%)
Selective reporting (reporting bias)Low riskAll relevant outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Takatori 2011

Methods
  • Study design: parallel RCT

  • Study duration: May 2005 to April 2007

  • Follow-up: 24 months

  • Loss to follow-up: 18/41 (43.9%)

Participants
  • Country: Japan

  • Setting: multicentre (23 centres)

  • Adult incident PD patients (CAPD/APD) with ESKD because of diabetic nephropathy

  • Number: treatment group (21); control group (20)

  • Mean age ± SD (years): treatment group (55.9 ± 11.16); control group (56.5 ± 9.86)

  • Sex (M/F): treatment group (14/7); control group (13/7)

  • Exclusion criteria: age < 18 years or > 80 years; urine volume < 400 mL/d; urinary tract obstruction due to neoplasm; neurogenic bladder; pregnancy; previous renal replacement therapies including PD, HD and kidney transplantation

Interventions

Treatment group

  • Treated with a maximum of 6 L of daily 1.5% or 2.5% Dianeal PD-2 or PD-4 in association with an overnight or daytime dwell of 2 or 1.5 L of 7.5% icodextrin-containing solution

Control group

  • Treated with a maximum of 8 L of daily 1.5% or 2.5% Dianeal PD-2 or PD-4 (Baxter)

Outcomes

Primary outcome

  • Rate at 2 years of PD technical survival

Secondary outcomes

  • Rate of decline in RRF

    • fluid status measured using body weight, blood pressure, cardiothoracic ratio on CXR, UF volume

    • RRF measured with daily urine volume renal CrCl, weekly Kt/V measured at baseline, 3, 6, 12, 18 and 24 months from the initiation of PD

  • Status of lipid and glucose metabolism

    • haemoglobin A1c, glycoalbumin, LDL-cholesterol, HDL-cholesterol, triglycerides

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot reported
Allocation concealment (selection bias)Unclear riskNot reported
Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: "open-label multicenter clinical trial". Given fluid balance is one of the major outcomes assessed, unblinded nature may have influenced introduction of co-intervention
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskHigh dropout rate - 18/41 (43.9%). However, the majority of dropouts (12) were due to reaching the primary endpoint (i.e. fluid overload), presence of attrition bias for other outcomes cannot be excluded
Selective reporting (reporting bias)Low riskAll relevant clinical outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Tranaeus 2000

Methods
  • Study design: open parallel RCT

  • Study duration: not stated

  • Follow-up period: 6 months with elective 6 month extension period

Participants
  • Countries: Europe, UK

  • Setting: multicentre (17 centres)

  • Prevalent adult patients on CAPD for at least 3 months, and being treated with 40 mmol/L lactate dialysate (Dianeal PD4) using an integrated disconnect system (Twin-bag) for at least 1 month; normalised (to BSA) GFR of ≤ 7 mL/min/1.73 m² (average of urea and CrCl) using 4 to 5 2-2.5 L exchanges/d, 7 days/wk, with no dry period; total weekly CrCl ≥ 55 L/ 1.73 m² BSA

  • Number: treatment group (70); control group (36)

  • Mean age, range (years): treatment group (55.1, 26.0 to 77.0); control group (56.6, 23.0 to 76.0)

  • Sex (M/F): treatment group (42/28); control group (18/18)

  • Exclusion criteria: acute or chronic exit site or tunnel infection; completed a course of antibiotics for exit site/ tunnel infection or peritonitis in the previous 30 days; other serious illnesses including the need for hospitalisation in the previous 30 days; HIV positive; pregnant or lactating; adding bicarbonate to bags or taking bicarbonate orally

Interventions

Treatment group

  • Bicarbonate-lactate buffered (25 mmol/L bicarbonate, 15 mmol/L lactate, pH 7.4) dialysis solution

Control group

  • Standard lactate-buffered (40 mmol/L lactate) dialysis solution (Dianeal PD4)

Outcomes
  • Peritoneal UF

  • Dialysis adequacy

  • Peritonitis

NotesFunding received from Baxter Healthcare, Ltd
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Open-label", however, unlikely to have influenced the objective outcomes measured
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High risk18/106 (17%) at 6 months; 13/57 (23%) at 12 months, dropout rate at 12 months not accounted for. Overall drop-out rate 62/106 (58.5%)
Selective reporting (reporting bias)Low riskAll relevant clinical outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Weiss 2009

Methods
  • Study design: open cross-over RCT

  • Study duration: not stated

  • Follow-up period: 24 weeks (+ pain assessment phase, but duration not specified)

Participants
  • Countries: Sweden, Netherlands, Switzerland

  • Setting: multicentre (16 centres)

  • Adult prevalent CAPD patients with no PD-related complications during the previous month.

  • Number: all patients (53); full set analysis (27); pain assessment analysis set ()

  • Mean age ± SD (years): all patients (60.9 ± 14.8); full set analysis (56.0 ± 16.8); pain assessment analysis set (58.7 ± 16.4)

  • Sex (M/F): all patients (31/22); full set analysis (16/11); pain assessment analysis set (15/8)

  • Exclusion criteria: not stated

Interventions
  • Patients randomly assigned to two groups, starting with either standard lactate-buffered PD fluid (SPDF) for 12 weeks (phase 1) and switching to bicarbonate-buffered PD fluid (bicPDF) for another 12 weeks (phase 2), or vice versa

  • After completing the biocompatibility study phase, pain assessment was performed to allow blinded administration of the solutions (4 exchanges - two with SPDF and two with bicPDF)

Outcomes
  • Biocompatibility markers in effluent and serum

    • Cancer antigen 125

    • hyaluronic acid

    • tumour necrosis factor-alpha

    • interleukin-6

    • vascular endothelial growth factor

    • interferon gamma

    • transforming growth factor-beta1

    • high-sensitivity C-reactive protein

  • RRF - GFR

  • Total fluid loss - peritoneal UF and urine volume in 24 hours

  • Peritoneal function - dialysate-to-plasma ratios of creatinine and urea

  • Acid-base parameters

  • Acid-base parameters

  • Pain assessment during exchange using McGill pain questionnaire

NotesStudy was supported by Fresenius Medical Care
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "A centralized randomization procedure was applied stratifying for diabetes status and time on PD"
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "open-label study", however during pain assessment phase the treatment was instituted in blinded manner. Other measured parameters are objective and unlikely to have been affected
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High riskHigh dropout rate, 19/53 (35.8%). Although all missing participants accounted for, but not reported at what stage. Difficult to be certain how many patients completed each phase of the study. Four patients did not participate in pain assessment phase and reasons not provided
Selective reporting (reporting bias)Low riskAll relevant clinical outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Wolfson 2002

Methods
  • Study design: open parallel RCT

  • Study duration: not stated

  • Follow-up period: 4 weeks - efficacy; 52 weeks - safety

Participants
  • Countries: Canada, USA

  • Setting: multicentre (32 - efficacy; 42 - safety)

  • Adult prevalent PD patients (CAPD only for efficacy; APD/CAPD for safety) with standard dialysis prescription for at least 30 days before screening that included a long dwell of 8-16 hours using a solution containing 2.5% dextrose at a fill volume of 2-2.5L

  • Number:

    • Efficacy study: treatment group (90); control group (85)

    • Safety study: treatment group (175); control group (112)

  • Mean age, range(years)

    • Efficacy study: treatment group (54.4, 22 to 82); control group (55.2, 26 to 86)

    • Safety study: treatment group (53.5, 22 to 83); control group (55.1, range 25 to 86)

  • Sex (M/F)

    • Efficacy study: treatment group (24/56); control group (26/59)

    • Safety study: treatment group (93/82); control group (50/62)

  • Exclusion criteria: not stated

Interventions

Treatment group

  • PD solution containing 7.5% icodextrin with PD-2 electrolytes (Extraneal; Baxter)

Control group

  • 2.5% dextrose (2.5% Dianeal with PD-2 or PD-4 electrolytes) for the long dwell (dwell time, 8 to 16 hours).

Dialysate volume was either 2L or 2.5L, depending on the patient's usual prescriptions

Outcomes

Efficacy study

  • Net UF during the long overnight dwell in CAPD patients

  • Also performed PET and calculated MTAC

Safety study

  • Mortality rate

  • Change from baseline in membrane transport characteristics using the PET

  • Incidence of adverse events

  • Plasma levels of total icodextrin and metabolites, and clinically meaningful changes in laboratory parameters

  • Chest radiographs

  • Fluid imbalances

  • Vital signs

  • Physical examinations

During the study period, group added quality of life assessment as part of the study protocol

NotesSponsored by Baxter
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer program
Allocation concealment (selection bias)Low riskCentral list maintained by personnel not directly involved with the study
Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blind status
Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble-blind
Incomplete outcome data (attrition bias)
All outcomes
High riskHigh dropout rate: 118/287 (41%); efficacy (12/175, 6.9%); safety (118/287, 41%)
Selective reporting (reporting bias)High riskLimited clinical outcomes reported
Other biasUnclear riskInsufficient information to permit judgement

Zeier 2003

  1. a

    APD - automated peritoneal dialysis; CAPD - continuous ambulatory peritoneal dialysis; CrCl - creatinine clearance; ESKD - end-stage kidney disease; GFR - glomerular filtration rate; HD - haemodialysis; PET - peritoneal equilibration test; PD - peritoneal dialysis; RCT - randomised controlled trial; UF - ultrafiltration

Methods
  • Study design: cross-over RCT

  • Study duration: not stated

  • Follow-up period: 16 weeks

Participants
  • Country: Germany

  • Setting: multicentre

  • Adult prevalent CAPD patients treated with exchange volumes of 1500 mL to 2500 mL

  • Number: treatment group A (9); treatment group B (6)

  • Mean age ± SD (years): treatment group A (49 ± 12); treatment group B (51 ± 8)

  • Sex (M/F): treatment group A (3/6); treatment group B (5/1)

  • Exclusion criteria: requirement of antibiotic treatment; history of peritonitis; seropositive for hepatitis B, C or HIV

Interventions
  • Group A

    • Patients were either first exposed to PD fluid with neutral pH, low GDP PD solution (Gambrosol trio, Gambro Co) during eight weeks and subsequently switched to conventional PD fluid (Gambrosol, Gambro Co) for subsequently 8 weeks

  • Group B

    • Patients received reversal of treatment sequence

Outcomes
  • Determine the fate of GDP in PD fluids during PD by performing ex vivo studies from collected PD effluent after each treatment period

  • CA125 concentrations from PD effluent

NotesAuthor contacted to obtain clinical parameters, awaiting response
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot stated
Allocation concealment (selection bias)Unclear riskNot stated
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot stated
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
High riskHigh dropout rate, 6/21 (28.6%)
Selective reporting (reporting bias)High riskLimited reporting of clinical outcomes. However, the primary purpose of the study was to examine the non-clinical effects (e.g. biomarkers) of GDP in biocompatible PD solutions
Other biasUnclear riskInsufficient information to permit judgement

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
BIOKID 2004Comparing two types of biocompatible peritoneal dialysis solutions
Boudville 2005Not RCT
Braide 2009Assessment of citrate supplementation rather than use of biocompatible peritoneal dialysis fluids
Dallas 2004Compared Icodextrin versus Icodextrin/glucose combination novel fluid
de Fijter 1993Study conducted over a short period with a view to assessing macrophage function hence study duration too short to evaluate pre-specified outcomes
Fang 2008Used neutral pH, low GDP PD solution as peritoneal equilibration test solution
Fischbach 2004Study conducted over two days to examine the effect of PD solutions on intraperitoneal pressure. Duration of study was too short to evaluate pre-specified patient level clinical outcomes
Hwang 2006Used Icodextrin as peritoneal equilibration test solution
Jenkins 2003Comparing the effect of icodextrin with novel combination solution composed of icodextrin and dextrose
John 2008Study conducted over one day to examine the effect of biocompatible PD solutions on baroreflex sensitivity. Duration of study was too short to evaluate pre-specified patient level clinical outcomes
La Milia 1999Not RCT of biocompatible PD solutions
Le Poole 2004Study includes amino acid-based dialysis solution
Liberek 2002Study conducted following 2 overnight dwells (one week apart) of biocompatible and conventional PD solutions to measure inflammatory markers in the PD effluent. Duration of study was too short to evaluate pre-specified patient level clinical outcomes
Martikainen 2005Study of amino acid-containing dialysis solution
Parikova 2007Used neutral pH, low GDP PD solution as a peritoneal equilibration test solution
Pedersen 1985Study comparing buffers in PD solution
Peers 1997Study of novel icodextrin/ glucose combination fluid
Pickering 2002Not RCT of biocompatible PD fluids
Plum 1997Study of amino acid-containing dialysis solution
Rodriguez-Carmona 2007Study including amino acid based dialysis solution
Sav 2009Comparing the use of twice-daily icodextrin versus daily icodextrin
Sav 2010Comparing the use of twice-daily icodextrin versus daily icodextrin
Selby 2005Study conducted over two days to examine the effect of PD solutions on haemodynamic parameters. Duration of study was too short to evaluate pre-specified patient level clinical outcomes
Smit 2000Used glycerol-based fluid
Smit 2001No biocompatible PD solution studied. Compared different strengths of glucose solutions
Stankovic-Popovic 2010Not RCT. Cross-sectional observational study
Ueda 2000Amino acid fluid study
Van Biesen 2004Amino acid fluid study
Vychytil 2008Not RCT
Wilflingseder 2009Letter

Characteristics of studies awaiting assessment [ordered by study ID]

Cho 2010

Methods
  • Study design: parallel RCT

  • Randomisation method: not stated

  • Blinding: not stated

  • Intention to treat: unclear

  • Follow-up period: 12 months

Participants
  • Country: Republic of Korea

  • Setting: single centre

  • Incident adult CAPD patients

Interventions

Group 1

  • 55 participants

  • Neutral pH, low GDP PD solution (Balance, Fresenius Medical Care, Germany)

Group 2

  • 23 participants

  • Conventional PD solution (Stay.safe, Fresenius Medical Care, Germany)

Group 3

  • 22 participants

  • Neutral pH, low GDP PD solution (Physioneal, Baxter Healthcare, USA)

Group 4

  • 26 participants

  • Conventional PD solution (Dianeal, Baxter Healthcare, USA)

Outcomes
  • UF volume

  • Glucose absorption

  • 24-hour peritoneal UF

  • Urine volume

  • Body weight

  • Bioimpedance analysis for fluid status assessment

NotesAbstract format only. Unable to obtain additional information from authors

Dai 2010

Methods
  • Study design: parallel RCT

  • Randomisation method: not stated

  • Blinding: double blind

  • Intention to treat: unclear

  • Follow-up period: 4 weeks

Participants
  • Country: China

  • Setting: single centre

  • CAPD patients

Interventions
  • 7.5% icodextrin (27) or glucose (27) at night for 4 weeks

Outcomes
  • 4-hour dialysate:plasma creatinine

  • UF volume

  • CrCl

NotesUnable to access full-text

Feriani 1993

Methods
  • Study design: cross-over RCT

  • Randomisation method: not stated

  • Blinding: open label

  • Intention to treat: unclear

  • Follow-up period: 6 weeks (inclusive of 2 weeks wash-out period)

Participants
  • Country: Italy

  • Setting: single centre

  • Prevalent adult continuous ambulatory peritoneal dialysis patients

Interventions

Group 1

  • After a control period (2 weeks) with a standard CAPD solution (lactate, 35 mmol/L), a two-chamber bag containing 34 mmol/L of bicarbonate was used for 4 weeks.

Group 2

  • Started with a two-chamber bag containing 34 mmol/L of bicarbonate for 4 weeks then changed to 2 weeks of standard CAPD solution (lactate, 35 mmol/L)

Outcomes
  • UF (mL/d)

  • Dialysate urea clearance (L/d)

  • Dialysate CrCl (L/d)

  • Renal urea clearance (mL/min)

  • Renal CrCl (mL/min)

NotesUnable to isolate data from the first phase of the cross-over study

Infante 2000

Methods
  • Study design: parallel RCT

  • Randomisation method: not stated

  • Blinding: not stated

  • Intention to treat: Unclear

  • Follow-up period: 12 months

Participants
  • Country: Italy

  • Setting: single centre, university hospital

  • Prevalent adult PD patients (24)

Interventions

Treatment group

  • Bicarbonate-buffered PD solution

Control group

  • Lactate-buffered PD solution

Outcomes
  • Mesothelial biomarkers (e.g. CA125)

NotesInformation available only in abstract form. Clinical outcomes of interest not available

Opatrna 2000

Methods
  • Study design: parallel RCT

  • Randomisation method: unclear

  • Blinding: not stated for participants, investigators and outcome assessors

  • Intention to treat: yes

  • Follow-up period: 3 months

  • Loss to follow-up: unclear

Participants
  • Country: Czech Republic

  • Setting: single centre

  • CAPD-treated patients with difficult hydration control versus a control group

Interventions
  • Icodextrin for the night-time exchange for a period of 3 months

Outcomes
  • UF

  • Blood pressure

NotesNo data given in the abstract for the control group

Rodriguez-Carmona 2012

Methods
  • Study design: cross-over design

  • Randomisation method: not stated

  • Blinding: open label

  • Intention to treat: Unclear

  • Follow-up period: 10 weeks

Participants
  • Country: Spain

  • Setting: single centre

  • Prevalent PD patients

  • Exclusion criteria: age < 18 or > 85 years; PD for < 2 months; significant clinical events (including peritonitis) during the previous 3 months; unwillingness or inability to cooperate

Interventions

Treatment group

  • Neutral pH, low GDP PD solution (Physioneal Clear Flex, Baxter)

Control group

  • Conventional PD solution (Dianeal, Baxter)

5 weeks in each arm then cross-over

Outcomes
  • Body weight

  • Urine output

  • RRF

  • Peritoneal small solute clearance

  • Peritoneal UF

  • 4-hour dialysate:plasma creatinine

NotesUnable to obtain data from the first phase of cross-over study

Yang 2002b

  1. a

    CAPD - continuous ambulatory peritoneal dialysis; PD - peritoneal dialysis; UF - ultrafiltration

Methods
  • Study design: cross-over RCT

  • Randomisation method: not stated

  • Blinding: open label

  • Intention to treat: unclear

  • Follow-up period: 8 weeks

Participants
  • Countries: Taiwan

  • Setting: single centre

  • Prevalent CAPD patients

Interventions
  • Received either 7.5% icodextrin or 2.5% dextrose for the overnight dwell for 28 days and then cross-over for another 28 days

Outcomes
  • UF

  • 4-hour dialysate:plasma creatinine

  • Blood pressure

NotesUnable to obtain data from the first phase of cross-over study

Characteristics of ongoing studies [ordered by study ID]

Tam 2006

  1. a

    AGE - advanced glycation end products; GDP - glucose degradation products; PD - peritoneal dialysis; PET - peritoneal equilibration test; UF - ultrafiltration

Trial name or titleEffect of low glucose degradation product peritoneal dialysis solution Gambrosol-Trio on residual renal function in patients receiving peritoneal dialysis - a randomized controlled trial
Methods
  • Countries: Canada, China

  • Setting: multicentre (3)

  • Study design: not stated

  • Randomisation method: not stated

  • Blinding: unclear

Participants

Adult PD patients

  • Inclusion criteria

    • Age 18 years or above; patients with PD catheter in situ

  • Exclusion criteria

    • Previous haemodialysis

    • Those unlikely to continue PD for less than six months (including anticipated kidney transplantation)

    • Previous renal transplant.

    • Incremental PD program

    • 24-hour urine volume < 100 mL or CrCl < 1 mL/min or both

Target patient number: 98

InterventionsUsual (standard) PD solution versus PD solution with low GDP
Outcomes
  • Peritoneal UF

  • Peritonitis episodes

  • Cardiovascular events (combination of non-fatal myocardial infarction, peripheral vascular disease requiring lower limb amputation, strokes, and deaths due to cardiovascular causes)

  • PET results

  • Peritoneal clearance of urea and creatinine

  • Changes in dialysate CA125 and AGE

Starting date

1/7/2005

Status - completed

Contact information

Dr Paul Tam

Scarborough, Canada

NotesUnable to obtain outcome of the study

Ancillary