Description of the condition
The Acute Dialysis Quality Initiative working group has developed the RIFLE criteria, an evidence-based consensus definition for acute kidney injury (AKI). RIFLE defines AKI severity ( R isk of kidney dysfunction, kidney I njury and kidney function F ailure) based on changes to serum creatinine (SCr) and urine output, and clinical outcomes (kidney L oss and E nd-stage kidney disease) (Bellomo 2004). Specific measures for AKI diagnostic criteria have been proposed as an increase in SCr to more than 300% from baseline, or more than 4.0 mg/dL with an acute increase of at least 0.5 mg/dL; or urine output less than 0.3 mL/kg/h in 24 hours, or anuria for 12 hours (Ronco 2007).
AKI is classified as pre-renal, intrinsic, and postrenal types (Guignard 1984). Pre-renal AKI affects up to 70% of patients and is principally caused by reduced blood flow to the kidneys; intrinsic AKI results from damage to kidney tissue and affects up to 40% of patients; postrenal AKI is caused by urinary tract obstruction and occurs in up to 10% of patients (Brady 1995). Sykes 2007 reports the predisposing factors for AKI "include massive haemorrhage, sepsis, diabetes, hypertension, cardiac disease, peripheral vascular disease, chronic renal impairment and age".
AKI is associated with significant morbidity and mortality, and has been variously estimated to affect nearly 15% of critically ill patients (Brivet 1996). however depending on the population in focus and diagnostic criteria applied, incidence rates from 1% to 25% have also been reported (Chertow 1998; De Mendonca 2000). Schrier 2004 reported mortality of 50% to 80% in critically ill patients with AKI admitted to intensive care. It has been estimated that mortality among patients with pre-renal AKI is 7% (Kaufman 1991) and 80% to 85% in patients who have multi-organ failure (Douma 1997; Spiegel 1991). Global AKI epidemiology also varies, but requirement for renal replacement therapy (RRT) among critically ill patients has been reported to be approximately 4% and hospital mortality 60% (Uchino 2006).
Description of the intervention
The goals of AKI treatment are to correct or treat underlying causes of kidney injury, support kidney function, and prevent or treat any complications. Current treatment calls for RRT - haemodialysis, peritoneal dialysis (PD) and, in extreme cases, kidney transplantation. In many centres, PD is favoured because it causes minimal cardiopulmonary instability and does not require anticoagulation (Hajarizadeh 1995). Haemodynamic stability is also thought to be enhanced as an effect of gradual removal of fluid and solutes (Passadakis 2007). Although PD has been considered to be less effective than haemodialysis and continuous RRT (CRRT) in patients with AKI, it remains an easily and simply instituted therapy, especially for infants and children (Passadakis 2007).
How the intervention might work
TPD is one form of automated PD (APD) which includes continuous APD (CAPD) and continuous equilibrating PD (CEPD; which is similar to CAPD except that the patients are not ambulatory). CAPD replaces some of the kidneys function by using the peritoneum to filter wastes and fluid out of the blood. TPD has been reported to be superior to CAPD and CEPD in terms of small molecule clearance. However some studies do not support this claim (Juergensen 2000; Piraino 1994; Perez 2000), producing conflicting results due to the many variables that affect the dialysis efficacy, and the small number of patients enrolled in the studies.
Why it is important to do this review
We sought to determine whether TPD was associated with better therapeutic effect and safety than other forms of PD to better inform clinical decision making about therapy for patients with AKI.
This review aimed to look at the benefits and harms of TPD versus any other form of PD for patients with AKI.
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 patients have been allocated to treatment with TPD or any other form of PD for AKI. The first period of randomised cross-over studies were also to be included.
Types of participants
Patients, regardless of sex or age, diagnosed with AKI) requiring RRT were eligible for this review. AKI was defined as an increase in SCr greater than 0.5 mg/dL (44 μmol/L) over baseline value or an increase of more than 50% over the baseline value; a reduction in creatinine clearance (CrCl) of more than 50%; elevated blood urea nitrogen (BUN) (Moore 1984; Solomon 1994; Zanardo 1994).
Studies enrolling patients with circumscribed peritonitis, abdominal wall infection, extensive peritoneal adhesions, or pregnancy were excluded.
Types of interventions
TPD versus any other form of PD used for patients with AKI.
Types of outcome measures
- Partial or complete recovery of kidney function
- Kidney function measures (CrCl, urea Kt/V, SCr, BUN, urine output, tubular proteins)
- Adverse events attributed to the intervention
- Protein loss
- Solute reduction indices (SRI). SRI measures the total amount of urea removed during a dialysis treatment. Kt/V measures the fractional change in blood urea concentration. SRI
Kt/V= 1 - e -Kt/VX 100
Search methods for identification of studies
We searched the Cochrane Renal Group's Specialised Register (February 2012) 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.
- Quarterly searches of the Cochrane Central Register of Controlled Trials CENTRAL.
- Weekly searches of MEDLINE OVID SP.
- Handsearching of renal-related journals & the proceedings of major renal conferences.
- Searching of the current year of EMBASE OVID SP.
- Weekly current awareness alerts for selected renal-journals.
- Searches of the International Clinical Trials Register (ICTRP) Search Portal & ClinicalTrials.gov.
Studies contained in the specialised register have been 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 and strategies used for this review.
Searching other resources
- Reference lists of nephrology textbooks, review articles and relevant studies.
- 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 search strategy described was used to obtain titles and abstracts of studies with potential relevance to the review. The titles and abstracts were screened independently by two authors, who discarded studies that were not applicable. However, we initially retained studies and reviews that might include relevant data or information on studies. Two authors independently assessed retrieved abstracts and, if necessary the full text, of these studies to determine which satisfied the inclusion criteria.
Data extraction and management
Data extraction was carried out independently by the same authors using standard data extraction forms. Studies not reported in English or Chinese were translated before assessment. Where more than one publication of one study existed, reports were to be grouped together and the most recent or most complete dataset used. Any discrepancy between published versions was to be highlighted.
Assessment of risk of bias in included studies
- 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?
Discrepancies were resolved by discussion with a third author.
Measures of treatment effect
Dichotomous outcomes results (mortality, recovery of kidney function) were to be expressed as risk ratios (RR) with 95% confidence intervals (CI). For continuous scales of measurement (CrCl, urea Kt/V, SCr, BUN, urine output, tubular proteins, protein loss, SRI) the mean difference (MD) was used, or the standardised mean difference (SMD) where different scales were used.
Unit of analysis issues
The first period of randomised cross-over studies was to be included.
Dealing with missing data
Any further information required from the original author was to be requested by written correspondence and any relevant information obtained in this manner 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
If sufficient studies were identified, we planned to examine for publication bias using a funnel plot (Higgins 2011).
Data were to be pooled using the random-effects model but the fixed-effect model was also used to ensure robustness of the model chosen and susceptibility to outliers.
Subgroup analysis and investigation of heterogeneity
Subgroup analysis was to be used to explore possible sources of heterogeneity (such as participants, interventions and study quality). Heterogeneity among participants could relate to age and renal pathology. Heterogeneity in interventions could relate to prior agent(s) used, and the agent, dose and duration of therapy. Adverse effects were to be tabulated and assessed using descriptive techniques.
Description of studies
Results of the search
The combined search of MEDLINE, EMBASE and CENTRAL identified a total of 185 articles of which 180 were excluded. Reasons for exclusion were:
- duplicate publications;
- non-RCTs; and
- RCTs of other interventions not stated in the inclusion criteria.
We assessed the full text of five potentially eligible studies. Of these, four were excluded because they did not relate to the intervention (TPD) or population (patients with AKI) (De Fijter 1994; Demetriou 2006; Holtta 2000; Kalra 1989). We therefore included one study enrolling 87 patients (Chitalia 2002). A flow chart of the study selection process is shown in Figure 1.
|Figure 1. Study flow diagram showing study identification and selection.|
We handsearched reference lists of identified articles but did not identify any additional studies that met our inclusion criteria.
Chitalia 2002 was a prospective, randomised cross-over study designed to explore the role of TPD and CEPD in patients with mild-to-moderate hypercatabolic AKI. this study evaluated the adequacy of both types of PD in terms of Kt/V (dialyser clearance, dialysis time, volume), normalised CrCl and modified SRI. Outcomes included Kt/V values; creatinine, urea, potassium and phosphate clearance; dextrose absorption; protein loss; and cost.
Risk of bias in included studies
|Figure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.|
|Figure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.|
This study clearly described the use of a random number table to generate the allocation sequence. The allocation concealment was unclear.
There was no specific statement describing blinding, however the interventions could not be blinded.
Incomplete outcome data
The number and reason for dropouts and withdrawals was not described; however, enrolled numbers and numbers reported for the measure of outcomes were the same.
We were unable to obtain the original protocol for Chitalia 2002, so we were unable to investigate selective outcome reporting. However this study did not report data relating to our primary outcomes of mortality and recovery of renal function.
Other potential sources of bias
The funding source of this study was not reported.
Effects of interventions
Mortality was not reported.
Partial or complete recovery of renal function
Partial or complete recovery of renal function was not reported.
Renal function measures
- The normalised CrCl (L/session/1.73 m² body surface area) for TPD and CEPD were 68.5 ± 4.43 and 58.85 ± 2.57, respectively. There was a significantly higher CrCl in the TPD group compared to the CEPD group ( Analysis 1.1: MD 1.88 mL/min, 95% CI 0.91 to 2.85). CrCl in the TPD group was 9.94 ± 2.93 mL/min and 6.74± 1.63 mL/min in the CEPD group (P = 0.001).
- The estimated weekly Kt/V values for TPD and CEPD were 2.43 ± 0.87 and 1.80 ± 0.32, respectively.
- BUN clearance was higher in the TPD group than in CEPD group ( Analysis 1.2: MD 14.71 mL/min, 95% CI 8.24 to 21.18). The mean urea clearances for TPD were reported as 19.85 ± 1.95 mL/min and 10.63 ± 2.62 mL/min for CEPD.
- TPD was superior to CEPD in the removal of potassium (24.56 ± 5.8 mL/min versus 16.81± 4.6 mL/min), phosphates (14.23 ± 5.4 mL/min versus 9.60 ± 3.90 mL/min) and in generating ultrafiltrate.
- SCr, urine output and tubular proteins were not reported.
Adverse events attributed to intervention
Adverse events were not reported.
Greater protein loss was reported in the TPD group (10.49 ± 1.55 g/session) compared to the CEPD group (6.63 ± 1.25 g/session) (P = 0.001).
Solute reduction indices (SRI)
TPD was better tolerated, consumed less time, and was less expensive than CEPD (Int$654.71 versus Int$717.55, respectively).
Summary of main results
Only one study that met our inclusion criteria was identified (Chitalia 2002). This study enrolled 87 patients with mild-to-moderate hypercatabolic AKI (excess UNA 12 g/d) who underwent 236 treatment sessions of PD (TPD 118, CEPD 118). This study reported the use of TPD resulted in higher BUN clearance and CrCl than CEPD; was superior to CEPD in the removal of potassium, phosphates and in generating ultrafiltrate; was better tolerated; consumed less time and was less expensive than CEPD. This study did not report mortality, recovery of renal function or any adverse events.
Overall completeness and applicability of evidence
We planned to include patients who had been allocated to treatment with TPD for AKI, however, only mild-to-moderate hypercatabolic rather than the severe hypercatabolic patients (rhabdomyolysis, multi-organ failure, and sepsis syndrome) were enrolled. Therefore, these findings may not apply to the patient population in the developed countries due to differences in aetiologies, co-morbidities and level of hypercatabolism (Chitalia 2002). We were unable to address all of the objectives of this review and the results are based on one small study. This study was inadequately powered to detect relevant differences between treatment effects; the enrolled population was poorly defined; and do not report our primary outcomes of interest (mortality, recovery of renal function). Any further studies conducted in this area must be well-designed RCTs assessing these primary outcomes.
Quality of the evidence
This review is based on evidence from only one cross-over RCT (Chitalia 2002) which compared 12 exchanges/session (1 session = 48 hours) for CEPD to 36 exchanges/session (1 session = 12 hours) for TPD. This resulted in daily comparisons of 12 L exchange (CEPD) versus 26 L (TPD). This is not a valid comparison. A more appropriate comparison would be IPD. It is therefore difficult to interpret the data. Similarly, the cost comparison of 12 hours versus 48 hours is misleading. No costs are included for the additional hours of care of TPD patients. In this one study, TPD with high flow rate (37 mL/min) yielded greater solute clearances and ultrafiltrate volume as compared to CEPD (9 mL/min), though the total volume of fluid used was the same. This is a source of bias since the better clearances with TPD are probably due to the higher dialysate flow rather than due to the tidal mode per se.
Potential biases in the review process
We searched for all relevant studies using sensitive and validated search strategies in several major medical electronic databases and other sources. It was, however, possible that not all the relevant studies be identified from computerized searching. In order to ensure a high degree of internal and external validity, we developed a comprehensive systematic review, rigid inclusion criteria for RCTs only, and a very comprehensive search strategy. Study identification, data extraction, data analysis, and method quality assessment for each study were performed by at least two independent investigators. However, only one RCT was included, Based on the limited number of RCTs comparing TPD with other PD modality used for patients with AKI, it is difficult to assess the benefits and risks of these treatment interventions. The small number of participants in the one included study, as well as its low quality, does not allow for a reliable conclusion. Our results were based on original studies and were therefore subject to the potential biases inherent in such studies. Potential limitations in this review include the lack of a uniform definition of AKI. In fact, until recently there was a universally recognised definition AKI by the Acute Kidney Injury Network (Mehta 2007). When looking at recent studies, our understanding of adequate PD has clearly moved away from focusing on small solute clearances. Indeed, several important studies show that small solute clearances (at least within the range studied) have no important influence on survival (Brown 2003; Paniagua 2002). In contrast, fluid balance and sodium balance have moved into the focus of interest in these patients. Further studies should assessing endpoint outcome measure, such as survival or mortality.
Agreements and disagreements with other studies or reviews
Few meta-analyses have been published in this area. A study by Holtta 2000 indicated that both TPD and continuous cyclic PD provided adequate dialysis for paediatric patients under and over five years of age, however the higher cost of TPD may restrict its use.
Implications for practice
The one RCT identified by this review evaluated TPD for the treatment of patients with AKI and was not designed to enable assessment of clinical outcome measures of efficacy. There was insufficient evidence to determine whether TPD was superior to any other mode of PD for the treatment of patients with AKI.
Implications for research
There is a need for more well-designed RCTs that compare the effects of TPD and other modes of dialysis for patients with AK). Cost-effectiveness analyses that account for patients' preferences are also required to enable clinicians to individualise optimal treatment. Pragmatic clinical outcome measures, such as mortality, recovery of renal function, and survival should be considered by future triallists. Adherence to study quality issues such as concealment of treatment allocation, blinding and long-term follow-up are required to enable evaluation of the risks and benefits of interventions in focus. Comprehensive reporting of trial methodology and outcomes that conform to the Consolidated Standards of Reporting Trials (CONSORT) statement should be undertaken by future triallists (Moher 2001).
- We would like to thank the referees for their editorial advice during the preparation of this review.
- We also thank to Dr ZHG Bai and Dr JY Tan for their constructive criticism that enabled us to improve the overall quality of this review.
- We would like to thank TX Liu for his extensive support during the entire editorial process.
Data and analyses
- Top of page
- Authors' conclusions
- Data and analyses
- Contributions of authors
- Declarations of interest
- Differences between protocol and review
- Index terms
Appendix 1. Electronic search strategies
Appendix 2. Risk of bias assessment tool
Protocol first published: Issue 1, 2008
Review first published: Issue 6, 2012
Contributions of authors
- Writing of protocol and review - Jiang L, Zeng R, Yang KH, Mi DH, Tian JH, Liu YL, Ma B
- Screening of titles and abstracts - Jiang L, Yang KH
- Assessment for inclusion - Jiang L, Mi DH
- Quality assessment - Jiang L, Zeng R, Tian JH
- Data extraction - Jiang L, Yang KH
- Data entry - Jiang L
- Data analysis - Jiang L, Yang KH, Tian JH
- Disagreement resolution - Yang KH, Tian JH
Declarations of interest
- Lei Jiang: none known
- Rong Zeng: none known
- KeHu Yang: none known
- Deng Hai Mi: none known
- Jin Hui Tian: none known
- Bin Ma: none known
- Yali Liu: none known
Differences between protocol and review
Risk of bias assessment tool has replaced the quality assessment checklist.
Medical Subject Headings (MeSH)
MeSH check words