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Interventions for protecting renal function in the perioperative period

  1. Mathew Zacharias1,*,
  2. Mohan Mugawar2,
  3. G Peter Herbison3,
  4. Robert J Walker4,
  5. Karen Hovhannisyan5,
  6. Pal Sivalingam6,
  7. Niamh P Conlon7

Editorial Group: Cochrane Anaesthesia, Critical and Emergency Care Group

Published Online: 11 SEP 2013

Assessed as up-to-date: 11 AUG 2012

DOI: 10.1002/14651858.CD003590.pub4


How to Cite

Zacharias M, Mugawar M, Herbison GP, Walker RJ, Hovhannisyan K, Sivalingam P, Conlon NP. Interventions for protecting renal function in the perioperative period. Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No.: CD003590. DOI: 10.1002/14651858.CD003590.pub4.

Author Information

  1. 1

    Dunedin Hospital, Department of Anaesthesia & Intensive Care, Dunedin, New Zealand

  2. 2

    St Vincent's University Hospital, Department of Anaesthesia and Intensive Care Medicine, Dublin, Ireland

  3. 3

    Dunedin School of Medicine, University of Otago, Department of Preventive & Social Medicine, Dunedin, New Zealand

  4. 4

    University of Otago, Department of Medicine, Dunedin, New Zealand

  5. 5

    Rigshospitalet, The Cochrane Anaesthesia Review Group, Copenhagen, Denmark

  6. 6

    Princess Alexandra Hospital, Department of Anaesthesia, Brisbane, Australia

  7. 7

    St Vincent's University Hospital, Department of Anaesthesia, Dublin, Ireland

*Mathew Zacharias, Department of Anaesthesia & Intensive Care, Dunedin Hospital, Great King Street, Dunedin, Private Bag 192, New Zealand. mathew.zacharias@otago.ac.nz. mzach@xtra.co.nz.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 11 SEP 2013

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Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

 
Summary of findings for the main comparison. Interventions in patients with pre-existing renal dysfunction

Interventions for protecting renal function in patients with pre-existing renal impairment who are undergoing surgery

Patient or population: patients with pre-existing renal impairment

Settings: perioperative period (7 days)

Intervention: interventions to protect the kidneys during the perioperative period

Comparison: placebo or no intervention

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No. of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Placebo or no interventionVarious interventions

Mortality in patients with pre-existing renal impairment

As reported in the included trials

Folliow-up: 7 days
Study populationOR 0.74 (0.36 to 1.52)959
(10 studies)
⊕⊝⊝⊝
very lowa,b,c,d
Evidence is not strong and is of poor quality

38 per 100029 per 1000
(15 to 56)

Moderate

20 per 100015 per 1000

(8 to 30)



Acute renal injury in patients with pre-existing renal impairment

As reported in the included trials

Follow-up: 1 to 7 days
Study populationOR 0.40 (0.22 to 0.76)979
(11 studies)
⊕⊝⊝⊝
very lowe,f,g,h
Evidence is not strong and is of poor quality (although it might give a statistical edge)

62 per 100028 per 1000
(15 to 50)

Moderate

40 per 100018 per 1000

(9 to 32)



*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in the footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; OR: Odds ratio.

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.

 aOnly six of the 10 studies showed low risk of bias.
bSignificant clinical heterogeneity between studies was noted.
cClinical heterogeneity and indications varied across the chosen studies.
dThe numbers of events and the total numbers of cases studied were small.
eOnly six of the 11 included studies were assessed as having low risk of bias.
fSsignificant clinical heterogeneity amongst the included studies was noted.
gClinical scenarios in the included studies varied.
hReported incidences were low and the numbers of participants in the included studies were small.

 Summary of findings 2 Interventions to protect the kidneys in the perioperative period in patients undergoing surgery: low ROB studies only

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Description of the condition

Intraoperative changes in renal blood flow and glomerular filtration rate are common. Postoperative renal dysfunction is mainly attributed to adverse events that occur during the perioperative period, including hypotension, hypovolaemia and sepsis, or it may be due to perioperative administration of contrast material (Morcos 2004). The reported risk of perioperative renal failure varies according to aetiology, definition and type of surgery; acute renal failure during the perioperative period is a serious complication associated with considerable morbidity and mortality. When postoperative renal dysfunction occurs, it is generally thought to be multi-factorial in nature.

 

Description of the intervention

Over the past few decades, attempts have been made to protect the kidneys both during surgery and in the immediate postoperative period (Wang 2003). Various regimens, such as low-dose dopamine, dopexamine, fenoldopam or diuretics, have been tried. The results are somewhat uncertain, hence a number of other measures have been tried. These include N-acetyl cysteine (Adabag 2008; Barr 2008; Burns 2005; Fischer 2005; Hynninen 2006; Prasad 2010; Ristikankare 2006), atrial natriuretic peptide (ANP) (Chen 2007; Mitaka 2008; Sezai 2000; Sezai 2009) and erythropoietin (EPO) (Song 2009). Amongst nephrologists, considerable enthusiasm has surrounded the potential for EPO to provide some renal protection (Johnson 2006).

Different tests, some simple and some complicated, are used with varying success to detect acute kidney injury (AKI) in the perioperative period. Measurement of urine output over a 24-hour period after surgery is one of the simpler tests. A commonly used measure is creatinine clearance, which is often examined by using the Cockcroft-Gault formula, which takes into consideration the age, body weight and sex of the individual, as well as serum creatinine levels. Glomurular filtration rate (GFR) can be measured, as can renal plasma flow. Other tests include assessment of the ability of kidneys to clear a water load (free water clearance) and to excrete sodium (fractional excretion of sodium).

Several newer tests are used as markers of renal damage. The ratio in urine of microalbumin to creatinine (Hynninen 2006; Turner 2008) has been used but is considered an index of kidney damage, most often in chronic kidney disease. Urinary N-acetyl-beta-D-glucosaminidase (U-NAG) to creatinine ratio (Hynninen 2006; Mitaka 2008), retinol-binding protein (RBP) to creatinine ratio and urinary neutrophil gelatinase-associated lipocalin (NGAL) to creatinine ratio are newer methods that can be used to detect renal damage; we have looked at these tests in preparing this update of the review. Plasma cystatin C (CysC) (Chen 2007; Haase 2007; Harten 2008; Hynninen 2006) is another available marker. In a recent study (Endre 2011), glutamytranspeptidase (GGT), alkaline phosphatase (ALP), NGAL, CysC, kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) were used in intensive care units as biomarkers of acute kidney injury.

 

How the intervention might work

Over the past few decades, several strategies have been used to attempt to protect the kidneys both during surgery and in the immediate postoperative period on a physiological basis (maintaining adequate cardiac output, maintaining renal vasodilatation, suppressing renal vasoconstriction and maintaining renal tubular flow). Various pharmacological regimens, such as use of low-dose dopamine, dopexamine, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors or diuretics, have been tried. Some success has been reported with such interventions (Welch 1995) but no clear evidence of success (Renton 2005) or of deterioration in renal function has been found (Lassnigg 2000).

Dopamine, an endogenous catecholamine, given at a dose of 2 µg·kg·min to 5 µg·kg·min (low-dose or renal dopamine), causes renal vasodilatation with a dose-dependent increase in renal blood flow (McDonald 1964; Seri 1988); at higher doses, dopamine augments renal blood flow by increasing cardiac output through β-adrenergic stimulation. The effect of dopamine has been studied extensively over the years (ANZICS CTG 2000). The net sum of these actions is seen as an increase in renal blood flow, an increase in GFR, diuresis and natriuresis. Mannitol, an osmotic diuretic, attenuates ischaemic reperfusion injury through multiple mechanisms, including maintenance of glomerular filtration pressure, prevention of tubular obstruction by cellular casts, scavenging of hydroxyl free radicals and prevention of cellular swelling (Schrier 1984). Furosemide, a loop diuretic, blocks ion transport activity in the medullary thick ascending loop of Henle and enhances tubular oxygen balance by decreasing tubular oxygen demand and consumption. However, loop diuretics also cause renal cortical vasodilatation, resulting in redistribution of blood flow, which could undermine the benefit previously described (Moitra 2009). Calcium channel blockers appear to confer protection against intracellular calcium injury in ischaemic reperfusion injury (Schrier 1991). Rapid administration of fluids results in expansion of intravascular volume, leading to an increase in cardiac output. ACE inhibitors alter the balance between the vasoconstrictive and salt-retentive properties of angiotensin ІІ and between the vasodilatory and natriuretic properties of bradykinin (Brown 1998). In the kidneys, ACE inhibitors decrease glomerular capillary pressure by decreasing arterial pressure and by selectively dilating efferent arterioles (Anderson 1986).

N-acetyl cysteine (NAC) has a variety of biological actions. It is an antioxidant (Zafarullah 2003); it stimulates endothelium-derived relaxing factor, thereby improving microvascular flow (Kiefer 2000); and it increases cyclic guanosine monophosphate (GMP) levels, thereby acting as a vasodilator and as an inhibitor of platelet aggregation. These various clinical actions might have led several investigators to focus on the use of NAC for the prevention of contrast-induced nephropathy (CIN) (Kay 2003; Tepel 2000). The natriuretic peptides play an important role in cardiovascular, renal and endocrine homeostasis. The natriuretic and diuretic actions of ANP are due to renal haemodynamic and direct tubular actions (Levin 1998). ANP increases GFR by increasing pressure within the glomerular capillaries (Marin-Grez 1986). ANP also inhibits angiotensin II-stimulated sodium and water transport in proximal tubules (Harris 1987), vasopressin-stimulated water transport in the collecting tubules (Dillingham 1986) and sodium absorption in the inner medullary collecting duct (Sonnenberg 1986). The combined effect of all of this consists of natriuresis and diuresis. Thus ANP has been used to try to counteract the two proposed pathophysiological mechanisms of decreased GFR in AKI, namely, reduced glomerular perfusion and tubular obstruction (Edelstein 1997). Accumulating evidence indicates that EPO has tissue protective or pleiotropic effects (Chatterjee 2005; Maiese 2005) that may be useful in preventing or treating AKI. The protective mechanisms are multi-factorial and involve inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways and promotion of recovery (Moore 2011).

 

Why it is important to do this review

The previously published version of this review (Zacharias 2008) was unable to detect much benefit derived from various interventions to protect the kidneys during the perioperative period. The efficacy of dopamine and its analogues, diuretics, calcium channel blockers, ACE inhibitors, NAC, ANP, sodium bicarbonate, EPO and antioxidants has yet to be proved in the capacity of reversing or preventing AKI during the perioperative period. In this updated review, we are taking a fresh look at the current status of this important topic.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

This review is aimed at determining the effectiveness of various measures advocated to protect patients' kidneys during the perioperative period.

We considered the following questions: (1) Are any specific measures known to protect kidney function during the perioperative period? (2) Of measures used to protect the kidneys during the perioperative period, does any one method appear to be more effective than the others? (3) Of measures used to protect the kidneys during the perioperative period,does any one method appear to be safer than the others?

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Criteria for considering studies for this review

 

Types of studies

We considered all randomized controlled trials of any intervention (dopamine and its analogues, diuretics, calcium channel blockers, ACE inhibitors, N-acetyl cysteine, atrial natriuretic peptides, hydration fluids or any other interventions) versus control (placebo or no intervention), published in any language.

 

Types of participants

We included participants undergoing all types of major surgery during which a specified intervention was used to protect the kidneys from possible damage during surgery. We did not include studies that specifically considered a paediatric population. We did not include studies with participants undergoing transplant surgery (heart, liver or kidney) because of the complexity of the surgery and the postoperative management required for these participants.

 

Types of interventions

We included studies that used the following interventions to maintain or protect kidney function during anaesthesia and surgery.

  • Dopamine and its analogues.
  • Diuretics.
  • Calcium channel blockers.
  • Angiotensin-converting enzyme (ACE) inhibitors.
  • Hydration fluids.
  • N-acetyl cysteine.
  • Atrial natriuretic peptide.
  • Erythropoietin (EPO).
  • Any other measures.

 

Types of outcome measures

 

Primary outcomes

Postoperative adverse outcomes. These included significant adverse outcomes: acute renal failure or death.

 

Secondary outcomes

Any changes in perioperative renal function. These included the following measures.

  • Urine output.
  • Creatinine clearance (or glomerular filtration rate).
  • Renal plasma flow (or renal blood flow).
  • Free water clearance.
  • Fractional excretion of sodium.
  • Urinary NAG/creatinine ratio.
  • Urinary RBP/creatinine ratio.
  • Plasma cystatin C.
  • Urinary NGAL/creatinine ratio.

 

Search methods for identification of studies

 

Electronic searches

In our updated review, we searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2012); MEDLINE (Ovid SP) (1966 to August 2012); and EMBASE (Ovid SP) (1988 to August 2012). We used the search strategies given in Appendix 1.

 

Searching other resources

We originally handsearched six major journals in anaesthesia and vascular or thoracic surgery (1985 to 2004).

  • Anesthesia and Analgesia.
  • Anesthesiology.
  • Annals of Surgery.
  • British Journal of Anaesthesia.
  • Journal of Thoracic and Cardiovascular Surgery.
  • Journal of Vascular Surgery.

However, because these journals are properly indexed in MEDLINE, we decided to rely on the electronic searches only without handsearching these journals from 2004 onwards.

 

Data collection and analysis

 

Selection of studies

We evaluated for appropriateness of inclusion all studies obtained by the search methods described above, as well as their abstracts and summaries. We obtained full publications for those studies, which required further assessment. Two of the review authors (MZ, NPC or PS or MM) evaluated these studies without prior consideration of the results, and consensus was reached on the final selection. Colleagues at the local hospital or university translated some of the selected studies into English.

 

Data extraction and management

We used specifically designed data extractions forms to extract the relevant data (Appendix 2). Two authors (MZ, NC or PS or MM) separately extracted and compared data. We resolved differences by discussion and reaching consensus. Wherever we considered it necessary, we attempted to contact the authors for further clarification, data, or both, with limited success.

The data collected included the following.

  • Reported mortality or acute renal failure.
  • Nature of the surgical intervention.
  • Nature of the intervention used.
  • Methodological quality (risk of bias) of the study.
  • Presence of pre-existing renal damage.
  • Any other relevant information.

Results of the individual studies were reported in many different ways, including means, standard deviations (SDs), standard errors of the mean (SEMs), median or interquartile ranges (IQRs) or ranges. We converted standard errors of the mean and interquartile ranges to standard deviations using appropriate formulae. We considered the interquartile range to be 1.35 times the standard deviation (for the purpose of this review, we assumed that the data were normally distributed). We calculated the standard deviation as the square root of the sample size times the standard error of the mean.

We considered creatinine clearance as a surrogate measure of GFR. When data involved weights, we made an assumption of 70 kg to convert the data. When data were presented in graphical form, we extracted the numerical data from the graphs as accurately as possible. We converted all data to uniform measurements; thus urine output, creatinine clearance, renal plasma flow and free water clearance were expressed in mL/min and fractional excretion of sodium as a percentage, urinary microalbumin/creatinine ratio as mg/mg, U-NAG (N-acetyl-beta-D-glucosaminidase)/creatinine ratio as mcmol/mmol, urinary retinol-binding protein/creatinine ratio as mcg/mmol, urinary NGAL (urinary neutrophil gelatinase-associated lipocalin)/creatinine ratio as ng/mmol and plasma cystatin C as mg/L.

In this review, we chose to look at data for the various renal function tests at 24 hours, two to three days and five to seven days, because these were the times that the results were most frequently reported in the selected studies. We were reluctant to look at data collected earlier than 24 hours because these would have shown acute changes brought on by anaesthesia and surgery. Even though it is not specified in most of the publications, we assumed that data on urine output at 24 hours reflect the average reading for urine output in the first 24 hours after surgery; the same applies to urine output results at two to four days and five to seven days postoperatively. For measurements such as creatinine clearance, renal plasma flow, free water clearance and fractional excretion of sodium, we assumed that the data were obtained at the specified time.

 

Assessment of risk of bias in included studies

At least two review authors independently assessed each included study for methodological quality on the basis of assessment of the following domains of quality: randomization, concealment of allocation, blinding and acknowledgement of dropouts. An overall quality assessment was rated as good, moderately good or poor (see  Table 1).

 

Measures of treatment effect

We pooled continuous outcomes with mean differences (MDs) and 95% confidence intervals (CIs). Initially, we pooled the results using a fixed-effect model, but substantial heterogeneity existed in many analyses, and we explored the reasons for this. Because of considerable heterogeneity seen in the results, we opted to present the data using a random-effects model.

Dichotomous outcomes (acute renal failure and mortality) were very rare events, hence we have presented these as odds ratios (ORs), using the Peto method.

 

Unit of analysis issues

We found no unit of analysis issues.

 

Dealing with missing data

We attempted to contact the authors of the publications to ask for information related to missing data, as well as further information on risk of bias.

 

Assessment of heterogeneity

Heterogeneity was assessed by visual inspection of forest plots, the test for heterogeneity and I2. We suspected significant heterogeneity on the basis of the I2 tests; values of I2 greater than 25% were regarded as moderate heterogeneity and values of I2 greater than 75% as significant heterogeneity) (Higgins 2008). Clinical heterogeneity was determined on the basis of clinical and demographic data provided in the studies.

 

Assessment of reporting biases

Reporting biases were assessed by using funnel plots constructed from the data.

 

Data synthesis

We used RevMan 5.1 for the synthesis of data (Deeks 2008). Continuous data are presented as MDs with 95% CIs. Because substantial heterogeneity was suspected, these results were pooled using a random-effects model. For dichotomous outcome data (primary outcomes, mortality and acute renal injury), we used a fixed-effect model because the incidence rate was very low; results are presented as ORs, using the Peto method.

 

Subgroup analysis and investigation of heterogeneity

We undertook subgroup analyses for the following situations.

  • Methods used for renal protection.
  • Types of operation.
  • Studies on participants with pre-existing renal dysfunction.

 

Sensitivity analysis

We undertook sensitivity analyses for randomized controlled trials using only studies with low or moderate risk of bias.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Description of studies

Details of studies can be found in 'Characteristics of included studies' and 'Characteristics of excluded studies'.

 

Results of the search

In the 2008 update (Zacharias 2008), we identified 136 studies from the MEDLINE search, 113 studies from the EMBASE search and 177 from CENTRAL (426 studies in total). We searched reference lists and bibliographical data from all retrieved articles and reviews for additional, relevant material. We sought information from authors of published studies and contacted recognized experts on this topic about any unpublished data. We identified a further 25 studies by this method. Thus in 2008, a total of 451 studies were considered potentially eligible for this review.

The extended search strategy in 2011 yielded 655 studies, and four studies were obtained from other sources. Of these, we obtained full papers for 35 studies and included 26 additional studies in the review. A further search in August 2012 provided a further 318 studies. From this group, we added one study to the review, one conference presentation to the list of studies awaiting further analysis and one exclusion due to duplicity. In this updated review, we have included 72 studies (Figure 1).

 FigureFigure 1. Study flow diagram, as of December 2012.

 

Included studies

See 'Characteristics of included studies'. The 72 included studies comprised a total of 4378 participants; 2291 of these received some form of intervention to protect the kidneys, and 2087 acted as controls. Of the 72 included studies, 13 had multiple arms (Barr 2008; Berendes 1997; Carcoana 2003; Colson 1992; Costa 1990; Dehne 2001; Donmez 1998; Dural 2000; Kleinschmidt 1997; Lassnigg 2000; Wahbah 2000; Yavuz 2002B; Zanardo 1993). We used the data from each arm separately for analysis of the interventions; whenever we did this, we adjusted (reduced) the numbers in the control groups in the appropriate sections. Barr 2008 had three arms; one arm used fenoldopam, one arm N-acetyl cysteine and another arm a combination of the two (the latter was excluded from the review). Berendes 1997 had three treatment arms with increasing strengths of dopexamine in cardiac surgery; another arm acted as control. We combined the three treatment groups for the purpose of analysis. Carcoana 2003 had three treatment arms and a control arm; one treatment group received dopamine infusion during the surgery, one group received a bolus of mannitol in the pump prime and the third group received both treatments. We excluded the third arm of the study. Colson 1992 had two treatment arms and one control arm; one treatment group received a calcium channel blocker, and the second group received an angiotensin-converting enzyme (ACE) inhibitor. Costa 1990 also had three arms-two treatment arms and one control arm; we excluded the arm that used multiple interventions (dopamine and SNP). Dehne 2001 had two control groups-one for participants with normal renal function and one for participants with pre-existing renal dysfunction. Intervention groups in this study (two) used dopexamine and matched the control for the presence or absence of pre-existing renal failure. Donmez 1998 used two intervention groups-one received verapamil and the other received nimodipine. Dural 2000 had three arms; one arm received dopamine, another arm received mannitol and the third arm was the control group. Kleinschmidt 1997 had two intervention groups-pentoxyfilline and gamma hydroxybutyrate-and one control group. Lassnigg 2000 had three arms-two active (dopamine or furosemide) and one control. In the case of Wahbah 2000, we used only one of three treatment arms because two arms combined multiple interventions (dopamine and mannitol, or dopamine and furosemide). This study contained a fourth control arm. Yavuz 2002B had three treatment arms and one control arm; one treatment arm used two interventions simultaneously, and we excluded this arm in the appropriate sections. Zanardo 1993 used two doses of dopamine by infusion; we combined the two groups in the analysis.

We identified three studies that were published both in abstract form and as full papers. We were unable to confirm whether they were duplicate papers and hence considered only the full papers for inclusion in the analysis (Kulka 1996; O'Hara 2002; Ryckwaert 2001) for this review. We have referred to the abstract publications (Kulka 1993; O'Hara 2002A; Ryckwaert 1995) in the table 'Characteristics of excluded studies'.

The details of participants' sex were not available for all studies, so we did not attempt to separately document this information. All included studies except one (Cregg 1999) involved adult populations; the Cregg study involved correction of scoliosis surgery and included a younger age group.

Forty-nine studies involved participants undergoing cardiac surgery (Adabag 2008; Amano 1994; Amano 1995; Ascione 1999; Barr 2008; Berendes 1997; Bergman 2002; Burns 2005; Carcoana 2003; Chen 2007; Cogliati 2007; Colson 1990; Costa 1990; Cregg 1999; Dehne 2001; Donmez 1998; Dural 2000; Durmaz 2003; Fischer 2005; Haase 2007; Haase 2009; Kaya 2007; Kleinschmidt 1997; Kramer 2002; Kulka 1996; Lassnigg 2000; Loef 2004; Marathias 2006; Morariu 2005; Morgera 2002; Myles 1993; Nouri-Majalan 2009; Prasad 2010; Prowle 2012; Ristikankare 2006; Ryckwaert 2001; Sezai 2000; Sezai 2009; Sezai 2011; Shim 2007; Song 2009; Tang 1999; Tang 2002; Urzua 1992; Witczak 2008; Woo 2002; Yavuz 2002A; Yavuz 2002B; Zanardo 1993). Fifteen trials included participants undergoing abdominal aortic surgery (for aortic aneurysm and occlusive arterial disease) (Colson 1992; Dawidson 1991; de Lasson 1995; de Lasson 1997; Halpenny 2002; Hynninen 2006; Lau 2001; Licker 1996; Mitaka 2008; Nicholson 1996; Pull Ter Gunne 1990; Shackford 1983; Turner 2008; Welch 1995; Wijnen 2002). Four trials consisted of participants undergoing biliary surgery (Gubern 1988; Parks 1994; Thompson 1986; Wahbah 2000); one involved laparoscopic colorectal surgery (Perez 2002); one partial nephrectomy (O'Hara 2002); and one correction of scoliosis (Cregg 1999). Fourteen studies involved participants with pre-existing renal dysfunction or those with increased risk of renal dysfunction as a result of the surgery (Adabag 2008; Burns 2005; Chen 2007; Cogliati 2007; Dehne 2001; Durmaz 2003; Haase 2007; Haase 2009; Marathias 2006; Nouri-Majalan 2009; Prasad 2010; Prowle 2012; Ristikankare 2006; Witczak 2008).

Various treatment measures were used in the different trials to protect the kidneys during the perioperative period. Interventions included dopamine and its analogue or agonist (dopexamine or fenoldopam) in 22 studies (Barr 2008; Berendes 1997; Carcoana 2003; Cogliati 2007; Costa 1990; Cregg 1999; de Lasson 1995; Dehne 2001; Dural 2000; Halpenny 2002; Lassnigg 2000; Myles 1993; O'Hara 2002; Parks 1994; Perez 2002; Tang 1999; Wahbah 2000; Welch 1995; Woo 2002; Yavuz 2002A; Yavuz 2002B; Zanardo 1993); diuretics (mannitol, furosemide) in six trials (Carcoana 2003; Dural 2000; Gubern 1988; Lassnigg 2000; Nicholson 1996; Shim 2007); calcium channel blockers (diltiazem, nicardipine, felodipine, verapamil, nimodipine) in nine trials (Amano 1995; Bergman 2002; Cho 2009; Colson 1992; de Lasson 1997; Donmez 1998; Witczak 2008; Yavuz 2002B; Zanardo 1993); ACE inhibitors (captopril, enalapril) in four trials (Colson 1990; Colson 1992; Licker 1996; Ryckwaert 2001); N-acetyl cysteine in seven trials (Adabag 2008; Barr 2008; Burns 2005; Fischer 2005; Hynninen 2006; Prasad 2010; Ristikankare 2006); atrial natriuretic peptide in five trials (Chen 2007; Mitaka 2008; Sezai 2000; Sezai 2009; Sezai 2011); and, in one trial each, glutathione (Amano 1994), prostaglandin (Morgera 2002), theophylline (Kramer 2002), clonidine (Kulka 1996), dexamethasone (Loef 2004; Morariu 2005), pentoxifylline (Kleinschmidt 1997), gamma hydroxybutyrate (Kleinschmidt 1997), antioxidant therapy (Wijnen 2002), phenylephrine (Urzua 1992), ursodeoxycholic acid (Thompson 1986) and preoperative haemodialysis (Durmaz 2003); and surgical measures such as off-pump cardiac surgery (Ascione 1999; Tang 2002) and an extraperitoneal approach to aortic surgery (Lau 2001). Five studies looked at the effects of hydration fluids (Dawidson 1991; Harten 2008; Marathias 2006; Pull Ter Gunne 1990; Shackford 1983). One trial (Song 2009) used erythropoietin (EPO) as the intervention. We have included this because it is currently an area of interest in this field.

We have conducted subgroup analyses of trials to observe the effects of different interventions on renal protection in the perioperative period. These subgroups included dopamine and its analogue or agonist; diuretics; calcium channel blockers; ACE inhibitors; atrial natriuretic peptide; N-acetyl cysteine; EPO; and hydration fluids. We also undertook subgroup analyses to observe the effects of the type of surgery; these included cardiac surgery, abdominal aortic surgery and biliary surgery. We performed a limited subgroup analysis of studies with pre-existing renal impairment.

We also completed a limited sensitivity analysis on studies with low risk of bias.

 

Excluded studies

We provide the reasons for excluding studies in the table 'Characteristics of excluded studies'. Studies published in languages other than English (German, Turkish, Serbian, Russian and Japanese) were translated with the help of volunteers. All of these studies were available as full publications. We have had only limited success in receiving adequate information and feedback from the authors whom we attempted to contact, in spite of repeated attempts. All included and excluded studies were published between 1976 and 2012. We did not include three studies in the analysis because we could not confirm that they were not duplicate publications (see below). We did not include three studies authored by Boldt et al because of issues surrounding the reliability of studies from that group of researchers.

 

Risk of bias in included studies

Even though we included 72 studies in the review, the overall methodological quality of the studies was poor. We used a quality assessment system (see 'Methodological quality of studies'  Table 1) based on method of randomization, allocation concealment, blinding and reporting of dropouts as the criterion. We scored the methodological quality of selected studies as good, moderately good or poor. When randomization, allocation concealment and blinding (participants, researchers, care givers and nurses) were adequately described and appropriately done, we classified the study as a good quality study. When randomization, allocation concealment and blinding (participants, researchers, care givers and nurses) were stated to have been done but no details were given in the publication, we classified the study as moderately good. When we found no evidence of allocation concealment and blinding, we classified the study as having poor methodological quality. The risk of bias information is given in Figure 2 and Figure 3.

The methodological quality assessment identified twelve studies of good quality (Adabag 2008; Burns 2005; Carcoana 2003; Cogliati 2007; Fischer 2005; Haase 2007; Haase 2009; Kaya 2007; Myles 1993; Prowle 2012; Song 2009; Turner 2008) and another nine studies for which the methodological quality was considered moderately good (Ascione 1999; Barr 2008; Cho 2009; de Lasson 1997; Hynninen 2006; Lassnigg 2000; Perez 2002; Ristikankare 2006; Shim 2007). Most of the studies that we assessed (51 studies) were classified as having poor methodological quality (see 'Methodological quality of studies', additional  Table 1). We had no success in obtaining data on concealment of allocation, blinding and method of randomization from most of the trial authors. Some trials were old, and we had very little chance of contacting these authors. We received replies from only five authors.

 FigureFigure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across 78 included studies.
 FigureFigure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

 

Allocation

See 'Characteristics of included studies' and  Table 1 for details.

 

Blinding

See 'Characteristics of included studies' and  Table 1 for details.

 

Incomplete outcome data

Data are available in 'Characteristics of included studies'.

 

Selective reporting

Funnel plots for primary outcomes, reported mortality and reported acute renal failure showed no evidence of selective reporting (see  Analysis 1.1 and  Analysis 1.2).

 

Other potential sources of bias

None of the publications mentioned any conflict of interest with respect to the choice of drugs used. The following studies acknowledged pharmaceutical company sponsorships: de Lasson 1995; de Lasson 1997; Halpenny 2002; Kramer 2002; Lassnigg 2000; and Thompson 1986.

We constructed funnel plots to detect publication bias in primary outcomes, mortality and acute renal injury (failure) but employed this approach only in studies that looked at participants with pre-existing renal damage and studies that were assessed to have low risk of bias.

 

Effects of interventions

See:  Summary of findings for the main comparison Interventions in patients with pre-existing renal dysfunction;  Summary of findings 2 Interventions to protect the kidneys in the perioperative period in patients undergoing surgery: low ROB studies only

We collected and analysed data from the selected 72 studies.

The dichotomous data (mortality and acute renal failure) consisted of rare events, so we used the Peto method of analysis and reported these results as Peto odds ratios (ORs) with 95% confidence intervals (CIs). We presented all continuous data results as mean differences (MDs) with 95% CIs. Results were plagued by heterogeneity throughout the analyses, so we used a random-effects model instead of a fixed-effect model. We undertook subgroup analysis for treatment measures and type of surgery. We were able to conduct only limited subgroup analysis for studies with pre-existing renal impairment because of the inadequate number of trials identified. A limited sensitivity analysis was done for studies with low risk of bias. To make the review less cumbersome for the reader, study results are listed in the text only when they were considered essential; references to appropriate 'Data and Analysis' tables are given.

 

Mortality

Data on perioperative mortality were reported in 41 studies, which included 3116 participants. Many cases of mortality were due to a combination of factors, including surgical causes and pathology. The risk of mortality was very low, and we did not perform a meta-analysis because of the significant clinical heterogeneity noted.

 

Acute renal injury

Acute renal injury (renal damage) in the postoperative period was reported in 44 studies. Many studies did not specify the criteria used to diagnose acute renal failure (ARF), hence we obtained information from these studies on the numbers of participants with acute renal injury requiring renal replacement therapy, in both treatment and control groups. Reported incidences were very low, and because of the significant clinical heterogeneity observed, we did not perform a meta-analysis of the data.

 

Effectiveness of measures used for renal protection

In this section, we tried to combine the data from the 72 identified studies to ascertain the effectiveness of treatments provided to protect the kidneys during the perioperative period compared with findings in the control population. Again, because of clinical heterogeneity in the form of different procedures and populations and decades of reporting such data, we decided to refrain from combining the data for a meta-analysis.

 

Effect of various interventions on renal protection

Most studies looked at dopamine and its analogues, although some trials used other measures to protect the kidneys during the perioperative period.

 

Dopamine or its analogues

Infusions of dopamine or its analogue (dopexamine) or agonist (fenoldopam) were used as treatment in 22 studies (Barr 2008; Berendes 1997; Carcoana 2003; Cogliati 2007; Costa 1990; Cregg 1999; de Lasson 1995; Dehne 2001; Dural 2000; Haase 2007; Halpenny 2002; Lassnigg 2000; Myles 1993; O'Hara 2002; Parks 1994; Perez 2002; Tang 1999; Wahbah 2000; Welch 1995; Woo 2002; Yavuz 2002A; Yavuz 2002B).

Mortality was reported in 11 trials (583 participants, OR 1.50, 95% CI 0.48 to 4.73, I2 = 25%; see  Analysis 1.1), and acute renal injury was reported in 10 trials (541 participants, OR 1.36, 95% CI 0.44 to 4.23, I2 = 63%; see  Analysis 1.2).

Urine output at 24 hours after operation was studied in 13 trials (see  Analysis 1.3.1). Considerable heterogeneity was observed (I2 = 92%), and no difference was noted between intervention and control groups (MD 0.18 mL/min, 95% CI -0.19 to 0.54). Urine flow at two to three days showed no significant increase with the intervention in seven studies (see  Analysis 1.3.2); the urine flow difference was 0.51 mL/min (95% CI 0.04 to 0.97), and heterogeneity was high (I2 = 95%). On the fifth to seventh day, treatment did not offer any advantages in five trials (see  Analysis 1.3.3) (MD 0.23 mL/min, 95% CI -0.06 to 0.51, I2 = 72%).

Creatinine clearance was studied in 15 trials after dopamine or its analogues were administered (see  Analysis 1.4). Fourteen trials reported creatinine clearance at 24 hours; nine studies at two to three days; and five studies at five to seven days after an operation. Analysis showed no significant difference between intervention and control groups at 24 hours (616 participants, MD 7.17 mL/min, 95% CI -5.53 to 19.86) and considerable heterogeneity (I2 = 91%); one study, in particular, favoured the treatment group (Berendes 1997). No differences were reported at two to four days (MD 7.31 mL/min, 95% CI -6.19 to 20.82, I2 = 94%) or at five to seven days after the operation (MD -3.33 mL/min, 95% CI -13.63 to 6.98, I2 = 18%).

Free water clearance in mL/min was looked at 24 hours after surgery in six trials (see  Analysis 1.5). Results showed no difference between treatment and control groups (MD 0.03 mL/min, 95% CI -0.17 to 0.22, I2 = 0%). Fractional excretion of sodium at 24 hours was reported in five trials (see  Analysis 1.6). As in the previous section, we did not analyse these data.

Renal blood flow in mL/min was studied at 24 hours after surgery in only two trials (see  Analysis 1.7) (de Lasson 1995; O'Hara 2002). No difference was noted (48 participants, MD 75.36 mL/min, 95% CI -63.27 to 213.98, I2 = 45%).

 

Diuretics

Mortality was reported in four trials (255 participants, OR 2.49, 95% CI 0.50 to 7.74, I2 = 0%; see  Analysis 2.1), and acute renal injury was reported in five trials (305 participants, OR 2.39, 95% CI 0.68 to 8.47, I2 = 35%; see  Analysis 2.2).

Mannitol or furosemide was used as treatment in six studies. Data were available for only five studies (see  Analysis 2.3). Urine output did not show a significant difference between groups at 24 hours in four studies (MD 0.10 mL/min, 95% CI -0.12 to 0.33, I2 = 0%; see  Analysis 2.3.1); at two to three days in three studies (MD 0.17 mL/min, 95% CI -0.06 to 0.40, I2 = 0%). No significant differences were noted on any occasion.

Creatinine clearance was measured at 24 hours in three studies. This measure showed no statistically significant differences (see  Analysis 2.4.1; MD -18.02 mL/min, 95% CI -41.78 to 5.75, I2 = 55%). The same was true on the second to fourth day (see  Analysis 2.4.2; MD 2.33 mL/min, 95% CI -14.76 to 19.42, I2 = 0%).

 

Calcium channel blockers

Mortality was reported in two trials (68 participants), and acute renal injury was reported in six trials (172 participants, OR 0.11, 95% CI 0.01 to 1.17; see  Analysis 3.1 and  Analysis 3.2, respectively).

Calcium channel blockers such as diltiazem, nicardipine and felodipine were used in nine studies. Four studies looked at urine output at 24 hours after treatment; no difference was observed between treatment and control groups (MD 0.23 mL/min, 95% CI 0.02 to 0.45, I2 = 0%; see  Analysis 3.3.1). Five studies looked at creatinine clearance at 24 hours postoperatively (see  Analysis 3.4.1). No advantage was derived from treatment (MD 4.74 mL/min, 95% CI -3.30 to 12.77, I2 = 57%). A total of 251 participants were included in the four studies.

Three studies measured free water clearance at 24 hours (see  Analysis 3.5.1) and reported no difference (MD -0.09 mL/min, 95% CI -0.47 to 0.29, I2 = 43%).

 

ACE inhibitors

Data were insufficient for calculations of risk of mortality and acute renal injury in this intervention group (see  Analysis 4.1 and  Analysis 4.2).

Four trials (Colson 1990; Colson 1992; Licker 1996; Ryckwaert 2001) looked at the usefulness of ACE inhibitors (enalapril or captopril) as renal protective agents. Data from three studies show that renal plasma flow in mL/min at the end of the operation (see  Analysis 4.3.1) was not significantly different (MD 46.37 mL/min, 95% CI -68.61 to 161.34, I2 = 0%).

 

Atrial Natriuretic Peptide

Mortality was reported in three trials (825 participants, OR 0.52, 95% CI 0.19 to 1.44, I2 = 48%; see  Analysis 5.1), and acute renal injury was reported in four trials (865 participants, OR 0.23, 95% CI 0.08 to 0.64, I2 = 0%; see  Analysis 5.2).

Five trials produced evidence for the use of atrial natriuretic peptide (ANP) (Chen 2007; Mitaka 2008; Sezai 2000; Sezai 2009; Sezai 2011). Much larger numbers of participants were included in Sezai 2009 and Sezai 2011 (789 participants), and this considerably influenced the meta-analysis.

Urine output at 24 hours showed no significant change in three studies; this favoured the intervention (4.82 mL/min, 95% CI -2.74 to 12.38, I2 = 100%; see  Analysis 5.3). Creatinine clearance at 24 hours in five studies showed similar results, favouring treatment by 4.31 mL/min (95% CI 0.34 to 8.28, I2= 99%; see  Analysis 5.4). Creatinine clearance at 2 to 3 days in four studies favoured the intervention (13.11 mL/min, 95% CI 13.11 to 13.76, but with I2 = 100%; see  Analysis 5.5). The poor methodological quality and the large heterogeneity (I2=100%) of the two dominant studies (Sezai 2009; Sezai 2011) make any conclusions worthless.

 

N-Acetyl Cysteine

Mortality was reported in six trials (641 participants, OR 1.01, 95% CI 0.42 to 2.42, I2 = 0%; see  Analysis 6.1), and acute renal injury was reported in five trials (601 participants, OR 0.91, 95% CI 0.32 to 2.62; I2 = 0%; see  Analysis 6.2).

Seven trials used administration of N-acetyl cysteine (NAC) as a measure to protect the kidneys intraoperatively (Adabag 2008; Barr 2008;Burns 2005; Fischer 2005; Haase 2007; Hynninen 2006; Prasad 2010; Ristikankare 2006). Urine output at 24 hours was estimated in two studies (146 participants). No differences were reported (0.23 mL/min, 95% CI -0.21 to 0.68, I2 = 47%).

 

Erythropoietin (EPO)

Recognition of EPO as a possible drug for renal protection is increasing, hence we reported data from the single available study. One study (Song 2009) used this drug in participants undergoing cardiac surgery, some of whom had pre-existing raised creatinine. The data are given in  Analysis 7.3,  Analysis 7.4 and  Analysis 7.5.

We estimated the risk of mortality with this intervention in one study (71 participants, OR 0.13, 95% CI 0.00 to 6.63; see  Analysis 7.1). The risk of acute renal injury was not estimable from this single intervention study (see  Analysis 7.2).

 

Intravenous fluid

Mortality was reported in four trials (152 participants, OR 0.75, 95% CI 0.16 to 3.42, I2 = 0%; see  Analysis 8.1), and acute renal injury was reported in three trials (123 participants, OR 0.22, 95% CI 0.05 to 0.96, I2 = 56%; see  Analysis 8.2).

Five trials studied the role of intravenous fluids such as colloids and hypertonic saline (Dawidson 1991; Harten 2008; Marathias 2006; Pull Ter Gunne 1990; Shackford 1983). Two studies (Pull Ter Gunne 1990; Shackford 1983) looked at creatinine clearance at 24 hours (see  Analysis 8.3.1), and no difference was noted (MD -10.34 mL/min, 95% CI -29.57 to 8.88, I2 = 0%).

 

Cardiac surgery

Forty-eight studies looked at the influence of different interventions in protecting the kidneys during cardiac surgery, and various measures were attempted.

 

Mortality

The risk of mortality (as reported in the trials) was estimated from 26 trials (2390 participants, OR 0.96, 95% CI 0.56 to 1.64, I2 = 10%; see  Analysis 9.1).

 

Acute renal injury

The risk of acute renal injury (as reported in the trials) was estimated from 31 trials (2504 participants, OR 0.55, 95% CI 0.32 to 0.92, I2 = 49%; see  Analysis 9.2).

 

Urine output

Seventeen studies (774 participants in the intervention groups and 701 participants in the control groups) looked at the influence of different interventions on urine output after cardiac surgery at 24 hours (see  Analysis 9.3.1). Urine output increased by 0.26 mL/min in the treatment group (95% CI 0.17 to 0.36) but with significant heterogeneity in the results (I2 = 86%). Nine studies (see  Analysis 9.3.2) looked at urine output two to three days after surgery. This measurement also showed no difference between intervention and control groups (MD 0.21 mL/min, 95% CI -0.13 to 0.54, I2 = 100%).

 

Creatinine clearance

Twenty-four studies (see  Analysis 9.4.1) looked at creatinine clearance after cardiac surgery at 24 hours in 1120 participants in the intervention groups and in 1016 participants in the control groups. The results suggested no significant improvement in creatinine clearance with treatment compared with control (MD 9.38 mL/min, 95% CI -5.99 to 24.74). Heterogeneity was high (I2 = 100%). Creatinine clearance was reported in 17 studies at two to three days after cardiac surgery (see  Analysis 9.4.2) and in seven studies on the fifth to seventh day (see  Analysis 9.4.3). Any evidence of beneficial effects of treatment in the later postoperative days was not clear because of the high heterogeneity of the results. Creatinine clearance improved on the second to third postoperative days (MD 14.21 mL/min, 95% CI 3.58 to 24.85, I2 = 100%) and on the fifth to seventh postoperative days (MD 14.99 mL/min, 95% CI 0.84 to 29.13, I2 = 97%). However, it is worthwhile noting that Sezai 2000, Sezai 2009 and Sezai 2011 (using atrial natriuretic peptide infusion as the treatment) estimated the GFR, which considerably favoured the treatment groups; the latter two studies included disproportionately high numbers of participants (789) and showed poor methodological quality.

 

Free water clearance

Free water clearance in mL/min was measured at 24 hours in seven studies (see  Analysis 9.5.1). The results suggested less water clearance with treatment at 24 hours (MD -1.81 mL/min, 95% CI -2.02 to -1.60), with significant heterogeneity (I2 = 98%). Again, Sezai 2009 has largely influenced the results. A difference was reported from the second to the third day in four studies (MD -3.55 mL/min, 95% CI -3.89 to -03.21) but with significant heterogeneity (I2 = 99%).

 

Fractional excretion of sodium

Eight studies documented fractional excretion of sodium at 24 hours, and three studies at two to three days postoperatively (see  Analysis 9.6).

 

Aortic surgery

 

Mortality

The risk of mortality (as reported in the trials) was estimated from eight trials (236 participants, OR 0.76, 95% CI 0.20 to 2.89, I2 = 5%; see  Analysis 10.1).

 

Acute renal injury

The risk of acute renal injury (as reported in the trials) was estimated from eight trials (284 participants, OR 0.62, 95% CI 0.11 to 3.70, I2 = 0%; see  Analysis 10.2).

 

Urine output

Seven studies measured urine output at 24 hours after elective aortic surgery. No demonstrable benefit was derived from treatment (see  Analysis 10.3.1; MD -0.04 mL/min, 95% CI -0.10 to 0.19, I2 = 0%). Two trials measured urine output on second and third postoperative days and on fifth and seventh postoperative days (see  Analysis 10.3.2 and  Analysis 10.3.3) and showed no difference with treatment (MD 0.26 mL/min, 95% CI -0.06 to 0.58, I2 = 12% and MD -0.09 mL/min, 95% CI -0.39 to 0.21, I2 = 23%, respectively).

 

Creatinine clearance

Ten studies (see  Analysis 10.4) looked at creatinine clearance after elective aortic surgery. All ten studies estimated creatinine clearance at 24 hours after surgery (see  Analysis 10.4.1), and the results suggested no benefit resulting from treatment (MD 7.99 mL/min, 95% CI -0.77 to 16.74, I2 = 22%). The same conclusions were drawn from five trials that measured creatinine clearance on the second to third postoperative days and on the fifth to seventh postoperative days (see  Analysis 10.4.2 and  Analysis 10.4.3). The MD were 11.62 mL/min (95% CI -6.13 to 29.37, I2 = 46%) and -12.85 mL/min (95% CI -26.41 to 0.72, I2 = 5%), respectively. It is interesting to note that heterogeneity was moderate in these results.

 

Free water clearance

Five trials studied this outcome at 24 hours after aortic surgery (see  Analysis 10.5.1). Results showed no significant benefit derived from treatment (MD -0.25 mL/min, 95% CI -0.51 to 0.01, I2 = 0%). Two studies looked at free water clearance on the second to fourth postoperative days and on the fifth to seventh postoperative days (see  Analysis 10.5.2 and  Analysis 10.5.3). No differences were noted (MD 0.37 mL/min, 95% CI -0.12 to 0.85, I2 = 0% and MD 0.24 mL/min, 95% CI -0.13 to 0.61, I2 = 0%, respectively).

 

Fractional excretion of sodium

Five studies reported this outcome (see  Analysis 10.6.1) at 24 hours, and two studies (see  Analysis 10.6.2) reported the results on the second to fourth postoperative days.

 

Renal plasma flow

Four trials estimated renal plasma flow after aortic surgery (see 'Data and analyses';  Analysis 10.7). Analysis of results at the end of the operation in two studies (see  Analysis 10.7.1) showed no statistically significant difference between treatment and control groups (MD 50.29 mL/min, 95% CI -92.83 to 193.40, I2 = 28%). The same held true for renal plasma flow at 24 hours after operation in two studies (see  Analysis 10.7; MD 45.86 mL/min, 95% CI -18.64 to 110.36, I2 = 0%).

 

Biliary surgery

 

Urine output

Only two trials looked at urine output at 24 hours, two to four days, and five to seven days after biliary surgery (see  Analysis 11.1). Some evidence from these two studies showed that urine output was less at 24 hours after an intervention was used (MD -0.59 mL/min, 95% CI -0.99 to -0.19, I2 = 18%), but it was not different at two to four days (MD 0.24 mL/min, 95% CI -0.22 to 0.69, I2 = 26%) and favoured control at five to seven days (MD 0.23 mL/min, 95% CI 0.09 to 0.37, I2 = 0%).

 

Creatinine clearance

Three trials measured creatinine clearance in mL/min at 24 hours (see  Analysis 11.2.1). No benefit was derived from the use of an intervention (MD -2.84 mL/min, 95% CI -14.07 to 8.39, I2 = 46%). The same was true for creatinine clearance values from three trials measuring creatinine clearance on the second to fourth postoperative days (see  Analysis 11.2.2; MD 0.42 mL/min, 95% CI -16.68 to 17.52, I2 = 8%) and from two trials at five to seven days postoperatively (MD 0.58 mL/min, 95% CI -16.43 to 17.60, I2 = 28%).

 

Pre-existing renal impairment

Fourteen studies included participants with pre-existing renal impairment or high risk of renal damage, although different criteria were used (Adabag 2008; Burns 2005; Chen 2007; Cogliati 2007; Dehne 2001; Durmaz 2003; Haase 2007; Haase 2009; Marathias 2006; Nouri-Majalan 2009; Prasad 2010; Prowle 2012; Ristikankare 2006; Witczak 2008). All of these trials involved participants undergoing cardiac surgery. Bergman 2002 used diltiazem infusions; Costa 1990 used dopamine or dopexamine infusions; Durmaz 2003 used preoperative haemodialysis; and Marathias 2006 used preoperative hydration. We identified an additional ten studies with pre-existing renal damage.

Ten studies looked at mortality. No differences were noted between treatment groups and control groups (OR 0.74, 95% CI 0.36 to 1.52, I2= 20%; see  Analysis 12.1). Participants who developed acute renal injury requiring renal dialysis were reported in eleven studies (OR 0.40, 95% CI 0.22 to 0.76, I2 = 37%; see  Analysis 12.2). Both of these analyses used the fixed-effect model because the incidence rate was very low. Studies were sufficient for the construction of funnel plots (Figure 4 and Figure 5); both suggested no significant publication bias.

 FigureFigure 4. Funnel plot of comparison: 12 Studies on participants with pre-existing renal impairment, outcome: 12.1 Mortality.
 FigureFigure 5. Funnel plot of comparison: 12 Studies on participants with pre-existing renal impairment, outcome: 12.2 Acute renal injury.

Four studies looked at urine output at 24 hours. The heterogeneity of these studies was large and hence precludes any conclusions; at 24 hours, the difference between intervention groups and control groups was 0.55 mL/min (95% CI 0.37 to 0.74 mL, I2 = 76%; see  Analysis 12.3.1), and at 2 to 3 days postoperatively, the difference was 0.48 mL/min (95% CI 0.32 to 0.64, I2 = 98%; see  Analysis 12.3.2). Four studies also looked at creatinine clearance at 24 hours, and the difference was insignificant (0.65 mL/min, 95% CI -0.75 to 2.06, I2 = 97%; see  Analysis 12.4.1). On postoperative days 2 to 3, the difference was 1.33 mL/min in three studies (95% CI -0.02 to 2.68, I2 = 95%; see  Analysis 12.4.2).

 

Low risk of bias studies

In this update, we identified 24 studies as having low risk of bias (Additional  Table 1, Characteristics of included studies), 12 of them being assessed as good (Adabag 2008; Burns 2005; Cogliati 2007; Fischer 2005; Haase 2007; Haase 2009; Kaya 2007; Myles 1993; Prowle 2012; Shim 2007; Song 2009; Turner 2008) and 12 assessed as moderately good (Ascione 1999; Barr 2008; Carcoana 2003; Cho 2009; Dawidson 1991; de Lasson 1995; de Lasson 1997; Hynninen 2006; Lassnigg 2000; Morariu 2005; Perez 2002; Ristikankare 2006). Data from these studies were subjected to sensitivity analysis. Unfortunately, reports on Perez 2002 contained data that were unsuitable for analysis, and this was confirmed by contact with the authors. We performed sensitivity analyses on the low risk of bias studies, and available data enabled us to report on mortality, acute renal impairment requiring renal supportive measures (dialysis) and urine output and creatinine clearance at 24 hours.

Nineteen studies reported mortality numbers (1604 participants,OR 1.01, 95% CI 0.52 to 1.97, I2= 0%; see  Analysis 13.1). Fifteen studies reported data on acute renal injury requiring dialysis (1600 participants, OR 1.05, 95% CI 0.55 to 2.03, I2= 1%; see  Analysis 13.2). Studies were sufficient for construction of funnel plots (Figure 6 and Figure 7); both suggested no significant publication bias.

 FigureFigure 6. Funnel plot of comparison: 13 Studies with low risk of bias: sensitivity analysis, outcome: 13.1 Reported mortality, low risk of bias studies only.
 FigureFigure 7. Funnel plot of comparison: 13 Studies with low risk of bias: sensitivity analysis, outcome: 13.2 Acute renal injury, requiring dialysis, low risk of bias studies only.

Urine output at 24 hours was reported in 11 studies; the difference was 0.20 mL/min (95% CI -0.04 to 0.44 mL/min, I2 = 71%; see  Analysis 13.3). Creatinine clearance at 24 hours was reported in nine studies, and the difference was 6.59 mL/min (95% CI -3.53 to 16.72 mL/min, I2 = 94%; see  Analysis 13.4).

Results suggested that even the low risk of bias studies, although few, showed no overall advantage for treatment versus control groups.

 

Assessment of small study bias

Funnel plots were examined for meta-analyses with 10 or more studies. Results showed no evidence of small sample biases (graphs not shown).

 

Summary of findings    [Explanations]

A summary of findings (SoF) table was developed using GradePro on studies with pre-existing renal impairment ( Summary of findings for the main comparison). The results suggest no advantage of interventions for mortality, but statistical evidence suggests that interventions might be helpful for reducing acute renal injury. However, it should be noted that the evidence is of low quality because clinical heterogeneity was considerable. Studies with low risk of bias ( Summary of findings 2) show no significant changes in reported perioperative mortality and in acute renal injury between intervention and control groups. Both SoF analyses suffer from low quality of evidence because of clinical heterogeneity and the small numbers of participants and events included in each study.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Summary of main results

Renal dysfunction after major surgery is one of the causes of postoperative morbidity and mortality. The cause of renal injury in the postoperative period is thought to be multi-factorial. Over the past three or four decades, many studies have tried to identify interventions that could provide renal protection during the perioperative period. Many different interventions have been tried, such as continuous infusions of dopamine or its analogues, use of diuretics such as mannitol and diligent use of ACE inhibitors and calcium channel blockers, to name a few. Drugs such as N-acetyl cysteine (NAC), atrial natriuretic peptide (ANP), sodium bicarbonate, antioxidants and erythropoietin (EPO) are some of the more recent interventions. None of these interventions appears to have a good evidence base.

We were unable to combine the whole data because of significant heterogeneity among selected studies. Given the large range of treatments, operation types and methods used to protect the kidneys, it is not surprising that heterogeneity is large. Heterogeneity could have been the result of multiple causes, including differences in the nature of treatment, the duration of treatment or participants' conditions, and of course it could have been related to the methodological quality of the studies. We used subgroup analyses to explore this further.

We performed subgroup analyses for the different interventions that were studied. Dopamine and its analogues showed no improvement in urine output or in other tests such as creatinine clearance, free water clearance or fractional excretion of sodium. Overall, on the basis of available studies, it appears that dopamine and its analogues do not offer much protection to the kidneys. It is worth noting that in a multi-centre study of participants in intensive care units (ANZICS CTG 2000), no significant benefit of dopamine was noted for these seriously ill individuals.

A 'Summary of findings' table, which used only low risk of bias studies, showed no benefit derived from interventions for domains of mortality and acute renal injury requiring dialysis. We looked at the effects of some of the major interventions (dopamine and its analogues, diuretics, calcium channel blockers, ACE inhibitors, atrial natriuretic peptide, N-acetyl cysteine, IV fluids and EPO) and major surgical procedures (cardiac surgery and abdominal aortic surgery), as well as groups of participants identified as having pre-existing renal damage; none of these groups showed a significant change in reported mortality or renal injury (as reported in the individual studies) in treatment groups versus control groups.

 

Overall completeness and applicability of evidence

Many physiological and biochemical variables can be used as markers of change in renal function. The various trials included in this review used numerous different markers as indicators of altered renal function. Each test has significant limitations, and results of the analysis must be interpreted in the context of these limitations.

  • Plasma creatinine is the most frequently measured marker of renal function. It is assumed that plasma creatinine remains constant and that clearance of creatinine occurs solely by glomerular filtration. Thus plasma creatinine is an indirect determinant of glomerular filtration rate (GFR). However, a greater than 50% reduction in GFR is needed before a change in plasma creatinine is seen. Plasma creatinine also reflects an individual's muscle mass, and alterations in muscle mass influence the plasma creatinine concentration, which does not reflect changes in GFR. A small amount of tubular excretion of creatinine occurs, which, in terms of normal GFR, is insignificant. However, with severe renal impairment, tubular secretion of creatinine has a greater role, and therefore plasma creatinine does not accurately reflect GFR. GFR is usually determined by the clearance of an inert substance, which is freely filtered at the glomerulus and has no tubular secretion or reabsorption. The gold standard has been estimation of inulin clearance. Creatinine clearance correlates well with GFR. For accuracy, it is essential that creatinine clearance is determined correctly. This requires a timed and complete collection of urine, along with a plasma creatinine determination. A variety of formulae have been derived that are based on plasma creatinine, body weight and age and are to estimate creatinine clearance and hence GFR. When renal function is stable, these estimates correlate well with measured GFR (r = 0.9).

  • Urine output is a non-specific measure of renal function. Clearly, if no urine is produced, then no glomerular filtration occurs. However, urine output can be influenced by several factors that regulate renal tubular handling of water. Oliguria (<400 mL urine/24 h) may just reflect excess salt and water retention by the kidney due to low fluid intake, not necessarily impaired renal function or the effects of increased antidiuretic hormone (ADH) release-a normal response to surgery or stress.

  • In clinical practice, renal blood flow is rarely determined, but this can be done by using clearance techniques using the Fick principle.

  • Free water clearance measures urinary concentrating ability. Any form of damage to the kidney impairs urinary concentrating ability. With renal tubular injury, free water clearance is impaired. Likewise, free water clearance is modified by diuretic therapy.

  • The fractional excretion of sodium has been used as a marker of renal function. More correctly, it reflects renal tubular reabsorption of sodium. The normal physiological response to a reduction in renal perfusion and glomerular filtration is to activate the tubular glomerular feedback mechanism, leading to increased reabsorption of sodium, along with water. The net effect consists of increased blood pressure and hence renal perfusion. In the acute situation (the first 24 hours after an event that affects renal function), low fractional sodium excretion (FeNa < 1%) indicates impaired renal perfusion. With any form of established renal damage, or the use of diuretics, the fractional excretion of sodium is increased and becomes impossible to interpret. It is, therefore, essential that the changes in markers of renal function that were recorded in the analysed papers are examined critically for the variables that influence reported measurements. Conclusions drawn from the results should be closely examined for the validity of the renal function measures that were used. An inability to correctly interpret the results prompted us to refrain from analysing the data on FeNa and instead to provide the raw data.

  • Newer advances in determining acute renal injury have been reported. These include use of various biomarkers such as urinary N-acetyl-beta-D-glucosaminidase (U-NAG) to creatinine ratio, urine retinol-binding protein (RBP) to creatinine ratio and urinary neutrophil gelatinase-associated lipocalin (NGAL) to creatinine ratio and blood plasma cystatin C levels. We have looked at these tests in this review update.

We believe it is important to emphasize that the lack of statistical significance described in this review could be due to many factors. We have already discussed heterogeneity as a significant factor; causes of heterogeneity include different types and durations of operations, gender differences, smoking status, state of nutrition, age, alcohol intake and co-morbidities such as hypertension, diabetes or other unknown causes. The potential role of publication (or small sample) bias is also important. One of the common methods employed to facilitate recognition of publication bias is the funnel plot. The most common reasons for small sample bias are the reluctance of trialists or journal editors to publish because results are non-statistically significant, but other reasons include small numbers of cases investigated in trials; lack of allocation concealment; and inadequate blinding. All of these events may result in misleading positive outcomes, leading to publication bias. Apart from visual examination of funnel plots, various complicated statistical methods are available, but none are wholly satisfactory for recognizing and avoiding small sample bias. A high level of suspicion is always required when reviews consisting of poor quality studies and studies with small sample sizes are interpreted, as with this review. Of particular concern are the high I2 values seen in many analyses; these may be due to significant statistical and clinical heterogeneity.

Results obtained with the use of diuretics were disappointing and suggested no real advantage for participants who received the treatment. The same is true for the use of calcium channel blockers and ACE inhibitors, both of which apparently offer no advantages. The use of hydration fluids also showed no obvious advantage for clear fluids over specialized colloid solutions, although the methodology of the studies and the information provided were of poor quality. It is interesting to note that only four studies investigated the role of different types of intravenous fluids in the perioperative setting, although in most studies participants were well hydrated. Wahbah 2000 makes special mention of the fluid status of participants. Is it simply that kidneys are at their happiest when they have a good pre-load to wash out toxic substances?

Other interventions such as N-acetyl cysteine and EPO have failed to show any advantage. It is a matter of note that a meta-analysis of studies using Atrial Natriuretic Peptides has shown some benefit of treatment in the form of improved creatinine clearance. However, caution is required in accepting these findings because two large studies conducted by one particular author reported an advantage of NAC over controls and considerably influenced the overall results (Sezai 2009; Sezai 2011).  

Potential renal damage in participants with pre-existing renal injury is widely recognized (Wijeysundera 2006). One area of interest for the authors of this review involved looking at the beneficial effects of treatment in participants with pre-existing renal impairment. Fortunately, we were able to include in this updated review 14 studies that considered this topic. These studies used different interventions. Unfortunately, available data are somewhat limited for the purpose of analysis. No difference was noted in reported mortality, but some advantage seems to be associated with treatment intervention, thus avoiding acute renal injury. Note that we have previously discussed differing criteria between studies for the diagnosis of acute renal damage. Urine output seems to improve when interventions are provided for patients with pre-existing renal damage, but the heterogeneity of the studies makes the results less valid.

We performed a sensitivity analysis of 24 studies of high and moderately high methodological quality. The results suggest no benefit for mortality or acute renal damage associated with treatment intervention. A marginal advantage seen in better urine output at 24 hours was offset by high heterogeneity, and no advantage was noted for creatinine clearance at 24 hours. These results substantiate the overall findings on questionable renal protection effects for various interventions given during the perioperative period.

It is important to remember that the effect of ADH is part of the usual stress response of surgery. Both urine output and free water clearance in the first 12 to 24 hours after surgery are reduced because of the influence of ADH (Brazel 1996). Fractional excretion of sodium is increased with the use of diuretics. Hence we would question the worth of measurements of urine output, free water clearance and fractional excretion of sodium as measures of renal function in the perioperative period. Glomerular filtration rate (and creatinine clearance) and renal plasma flow are good measures of renal function, but these must be measured accurately if meaningful conclusions are to be drawn.

 

Quality of the evidence

A major outcome of interest, mortality, was reported in a number of studies. Only a small number of deaths were reported in the trials, and this review shows that no advantage was conferred by individual interventions. Similarly, another outcome of major importance, acute renal injury after operation, was reported in only a few of the included studies. No evidence suggests that specific interventions offered any advantages for participants. However, it is important to recognize that the methodological quality of many of the included studies was poor and that the number of reported cases was small. Another point to consider is the inconsistency of the criteria used to diagnose renal injury across multiple studies. As a result, the statistical significance may not indicate a true advantage of interventions over no interventions.

In the subgroup of surgical procedures, cardiac surgery, aortic surgery and biliary surgery were considered for analysis. In cardiac surgery, interventions helped to increase urine output at 24 hours after surgery, but a high level of heterogeneity made the results unconvincing. Creatinine clearance also improved slightly at two to three days and five to seven days after surgery with treatment given to participants undergoing cardiac surgery, ,but the results are considerably swayed by the studies conducted by Sezai et al (Sezai 2009; Sezai 2011). None of the other tests showed any significant changes. Reported mortality and acute renal injury were no different after cardiac surgery and after abdominal aortic surgery.

No benefit was noted in other forms of interventions and surgery. However, the number and quality of studies in these areas are limited.

 

Potential biases in the review process

Even though we included 72 studies in this review, the overall methodological quality of the studies was poor. The methodological quality assessment identified twelve studies of good quality and another nine studies in which the methodological quality was considered moderately good. Most of the studies that we assessed (51 studies) were classified as showing poor methodological quality. This would reflect on any conclusions drawn from this review.

A note of caution: Many of the studies included in this review are old and were conducted before adaptations were made to the RIFLE (risk, injury, failure, loss of kidney function and end-stage kidney disease) classification, which was introduced in 2004 (Bellomo 2007), and to acute kidney injury (AKI) diagnosis and classification criteria, introduced in 2007 (Mehta 2007). These classifications are generally accepted in modern clinical practice and research (Lopes 2013). So that the reader might find no uniformity or consistency for the diagnosis or classification of renal damage in many of the older studies included in this review; we have taken the criteria and diagnosis used by the authors. Any future update of this review should include a subgroup of studies conforming to such classification as RIFLE or AKI.

Another area of concern was that we were unable to standardize the administration or withholding of various medications, which may or may not have influenced individual study results.

 

Agreements and disagreements with other studies or reviews

Results of this review reflect previous versions of the review (Zacharias 2005; Zacharias 2008). A recent systematic review, undertaken to look at renal protection offered by perioperative haemodynamic manipulation, looks at the effects of haemodynamic stabilization and the effects of inotropes and fluids or a combination of these (Brienza 2009). Although we are reluctant to comment on the methodological rigor of the Brienza review, it is of note that this review agrees with the present review on the use of fluids as a measure to protect renal function, showing no clear advantage for fluid management alone. However, the focus of our review is exploration of the effects of pharmacological agents used in the perioperative period.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

 

Implications for practice

No convincing evidence suggests that pharmacological or other interventions used to protect the kidneys during surgery are of benefit to patients, as seen from 72 included studies. Reasonable numbers of studies are currently available to substantiate this point. It is also of note that we were unable to find any significant adverse effects associated with the various interventions.

 
Implications for research

Many studies are available on the use of various pharmaceutical agents to protect renal function during surgery. Further areas of possible research might include the use of newer methods of identifying acute renal damage, such as urinary biomarkers. Future studies should focus on evaluation of preventive measures or more precise and accurate methods of identifying the benefit or harm of interventions. Use of RIFLE or AKI classification to identify renal damage would result in better comparisons of the effects of interventions and procedures.

Feedback

Please forward any comments and feedback to Jane Cracknell (jane_cracknell@yahoo.com), Managing Editor, Cochrane Anaesthesia Review Group.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

We would like to thank Anna Lee, Nathan Pace, Mike Bennett, Giovanni Strippoli, Giuseppe Remuzzi, Amy Arkel, Janet Wale and Nete Villebro, as well as Suetonia Palmer, Marliers Ostermann and Giovanni Strippoli, for their valuable suggestions during the editorial process of preparing the previous review (Zacharias 2005) and this review. We are very grateful to Dr Ian Gilmore for his contribution as co-author to the previous versions of this review. Our special thanks to Jane Cracknell, the Co-ordinator for the Cochrane Anaesthesia Review Group, for her encouragement, support, help and great patience. We thank Dolores Matthews for the copy editing of this review.

We are also grateful to Toni Yalovitch, Mina Nishimori and Murat Genc for their assistance with manuscript translation, from Slovakian, Japanese and Turkish, respectively.

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
Download statistical data

 
Comparison 1. Dopamine and analogues versus no intervention

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality11583Peto Odds Ratio (Peto, Fixed, 95% CI)1.50 [0.48, 4.73]

 2 Acute renal injury10541Peto Odds Ratio (Peto, Fixed, 95% CI)1.36 [0.44, 4.23]

 3 Urine output13Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 24 hours (mL/min)
13670Mean Difference (IV, Random, 95% CI)0.18 [-0.19, 0.54]

    3.2 2 to 4 days (mL/min)
7380Mean Difference (IV, Random, 95% CI)0.51 [0.04, 0.97]

    3.3 5 to 7 days (mL/min)
4103Mean Difference (IV, Random, 95% CI)0.23 [-0.06, 0.51]

 4 Creatinine clearance15Mean Difference (IV, Random, 95% CI)Subtotals only

    4.1 24 hours (mL/min)
14616Mean Difference (IV, Random, 95% CI)7.17 [-5.53, 19.86]

    4.2 2 to 4 days (mL/min)
9459Mean Difference (IV, Random, 95% CI)7.31 [-6.19, 20.82]

    4.3 5 to 7 days (mL/min)
5115Mean Difference (IV, Random, 95% CI)-3.33 [-13.63, 6.98]

 5 Free water clearance6Mean Difference (IV, Random, 95% CI)Subtotals only

    5.1 24 hours (mL/min)
6166Mean Difference (IV, Random, 95% CI)0.03 [-0.17, 0.22]

 6 Fractional excretion of sodium5Mean Difference (IV, Random, 95% CI)Totals not selected

    6.1 24 hours (%)
5Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 7 Renal plasma flow (24 hours)248Mean Difference (IV, Random, 95% CI)75.36 [-63.27, 213.98]

 
Comparison 2. Diuretics versus no intervention

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality4255Peto Odds Ratio (Peto, Fixed, 95% CI)2.49 [0.80, 7.74]

 2 Acute renal injury5305Peto Odds Ratio (Peto, Fixed, 95% CI)2.39 [0.68, 8.47]

 3 Urine output4Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 24 hours (mL/min)
4141Mean Difference (IV, Random, 95% CI)0.10 [-0.12, 0.33]

    3.2 2 to 4 days (mlL/min)
289Mean Difference (IV, Random, 95% CI)0.15 [-0.14, 0.45]

 4 Creatinine clearance4Mean Difference (IV, Random, 95% CI)Subtotals only

    4.1 24 hours (mL/min)
3123Mean Difference (IV, Random, 95% CI)-18.02 [-41.78, 5.75]

    4.2 2 to 4 days (mL/min)
3120Mean Difference (IV, Random, 95% CI)2.33 [-14.76, 19.42]

 
Comparison 3. Calcium channel blockers versus no intervention

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality268Peto Odds Ratio (Peto, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Acute renal injury6172Peto Odds Ratio (Peto, Fixed, 95% CI)0.11 [0.01, 1.17]

 3 Urine output4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    3.1 Urine output: 24 hours (mL/min)
4170Mean Difference (IV, Fixed, 95% CI)0.23 [0.02, 0.45]

 4 Creatinine clearance5Mean Difference (IV, Random, 95% CI)Subtotals only

    4.1 24 hours (mL/min)
5251Mean Difference (IV, Random, 95% CI)4.74 [-3.30, 12.77]

    4.2 2 to 4 days (mL/min)
2130Mean Difference (IV, Random, 95% CI)13.92 [-24.62, 52.46]

 5 Free water clearance3Mean Difference (IV, Random, 95% CI)Subtotals only

    5.1 24 hours (mL/min)
391Mean Difference (IV, Random, 95% CI)-0.09 [-0.47, 0.29]

 
Comparison 4. ACE inhibitors versus no intervention

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality114Peto Odds Ratio (Peto, Fixed, 95% CI)7.39 [0.15, 372.38]

 2 Acute renal injury364Peto Odds Ratio (Peto, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Renal plasma flow3Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 RPF: end of operation (mL/min)
362Mean Difference (IV, Random, 95% CI)46.37 [-68.61, 161.34]

 
Comparison 5. Atrial natriuretic peptide versus no intervention

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality3825Peto Odds Ratio (Peto, Fixed, 95% CI)0.52 [0.19, 1.44]

 2 Acute renal injury4865Peto Odds Ratio (Peto, Fixed, 95% CI)0.23 [0.08, 0.64]

 3 Urine output at 24 hours3584Mean Difference (IV, Random, 95% CI)0.42 [0.18, 0.67]

 4 Creatinine clearance, 24 hours5905Mean Difference (IV, Random, 95% CI)35.23 [-0.48, 70.94]

 5 Creatinine clearance, 2 to 3 days5905Mean Difference (IV, Random, 95% CI)27.30 [4.36, 50.23]

 
Comparison 6. N-Acetyl cysteine versus no intervention

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality6641Peto Odds Ratio (Peto, Fixed, 95% CI)1.01 [0.42, 2.42]

 2 Acute renal injury5601Peto Odds Ratio (Peto, Fixed, 95% CI)0.91 [0.32, 2.62]

 3 Urine output, 24 hours2146Mean Difference (IV, Random, 95% CI)0.18 [-0.24, 0.60]

 
Comparison 7. Erythropoietin (EPO) versus control

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality171Peto Odds Ratio (Peto, Fixed, 95% CI)0.13 [0.00, 6.63]

 2 Acute renal injury171Peto Odds Ratio (Peto, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Urine output: 24 hours171Mean Difference (IV, Random, 95% CI)-0.13 [-0.47, 0.21]

 4 Urine output: 2 to 3 days171Mean Difference (IV, Random, 95% CI)-0.19 [-0.56, 0.18]

 5 Urine output: 5 to 7 days171Mean Difference (IV, Random, 95% CI)-0.14 [-0.50, 0.22]

 
Comparison 8. Intravenous fluid versus control

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality4152Peto Odds Ratio (Peto, Fixed, 95% CI)0.75 [0.16, 3.42]

 2 Acute renal injury3123Peto Odds Ratio (Peto, Fixed, 95% CI)0.22 [0.05, 0.96]

 3 Creatinine clearance2Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 24 hours (mL/min)
277Mean Difference (IV, Random, 95% CI)-10.34 [-29.57, 8.88]

 
Comparison 9. Cardiac surgery: subgroup analysis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality262390Peto Odds Ratio (Peto, Fixed, 95% CI)0.96 [0.56, 1.64]

 2 Acute renal injury312504Peto Odds Ratio (Peto, Fixed, 95% CI)0.55 [0.32, 0.92]

 3 Urine output19Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 24 hours (mL/min)
171475Mean Difference (IV, Random, 95% CI)0.26 [0.17, 0.36]

    3.2 2 to 3 days (mL/min)
91058Mean Difference (IV, Random, 95% CI)0.21 [-0.13, 0.54]

 4 Creatinine clearance27Mean Difference (IV, Random, 95% CI)Subtotals only

    4.1 24 hours (mL/min)
242136Mean Difference (IV, Random, 95% CI)9.38 [-5.99, 24.74]

    4.2 2 to 3 days (mL/min)
171844Mean Difference (IV, Random, 95% CI)14.21 [3.58, 24.85]

    4.3 5 to 7 days (mL/min)
7949Mean Difference (IV, Random, 95% CI)14.99 [0.84, 29.13]

 5 Free water clearance8Mean Difference (IV, Random, 95% CI)Subtotals only

    5.1 24 hours (mL/min)
7700Mean Difference (IV, Random, 95% CI)-0.02 [-0.22, 0.19]

    5.2 2 to 3 days (mL/min)
4591Mean Difference (IV, Random, 95% CI)-0.29 [-0.30, -0.28]

 6 Fractional excretion of sodium9Mean Difference (IV, Random, 95% CI)Totals not selected

    6.1 24 hours (%)
8Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    6.2 2 to 4 days (%)
3Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 10. Aortic surgery: subgroup analysis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality8236Peto Odds Ratio (Peto, Fixed, 95% CI)0.76 [0.20, 2.89]

 2 Acute renal injury8284Peto Odds Ratio (Peto, Fixed, 95% CI)0.62 [0.11, 3.70]

 3 Urine output7Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 24 hours (mL/min)
7227Mean Difference (IV, Random, 95% CI)0.04 [-0.10, 0.19]

    3.2 2 to 3 days (mL/min)
395Mean Difference (IV, Random, 95% CI)0.26 [-0.06, 0.58]

    3.3 5 to 7 days (mL/min)
255Mean Difference (IV, Random, 95% CI)-0.09 [-0.39, 0.21]

 4 Creatinine clearance9Mean Difference (IV, Random, 95% CI)Subtotals only

    4.1 24 hours (mL/min)
9323Mean Difference (IV, Random, 95% CI)7.99 [-0.77, 16.74]

    4.2 2 to 3 days (mL/min)
5195Mean Difference (IV, Random, 95% CI)11.62 [-6.13, 29.37]

    4.3 5 to 7 days (mL/min)
4116Mean Difference (IV, Random, 95% CI)-12.85 [-26.41, 0.72]

 5 Free water clearance5Mean Difference (IV, Random, 95% CI)Subtotals only

    5.1 24 hours (mL/min)
5154Mean Difference (IV, Random, 95% CI)-0.25 [-0.51, 0.01]

    5.2 2 to 4 days (mL/min)
285Mean Difference (IV, Random, 95% CI)0.37 [-0.12, 0.85]

    5.3 5 to 7 days (mL/min)
285Mean Difference (IV, Random, 95% CI)0.24 [-0.13, 0.61]

 6 Fractional excretion of sodium5Mean Difference (IV, Random, 95% CI)Totals not selected

    6.1 24 hours (%)
5Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

    6.2 2 to 4 days (%)
2Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]

 7 Renal plasma flow4Mean Difference (IV, Random, 95% CI)Subtotals only

    7.1 End of operation (mL/min)
244Mean Difference (IV, Random, 95% CI)50.29 [-92.83, 193.40]

    7.2 24 hours (mL/min)
247Mean Difference (IV, Random, 95% CI)45.86 [-18.64, 110.36]

 
Comparison 11. Biliary surgery: subgroup analysis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Urine output2Mean Difference (IV, Random, 95% CI)Subtotals only

    1.1 Urine output: 24 hours (mL/min)
243Mean Difference (IV, Random, 95% CI)-0.59 [-0.99, -0.19]

    1.2 Urine output: 2 to 4 days (mL/min)
243Mean Difference (IV, Random, 95% CI)0.24 [-0.22, 0.69]

    1.3 Urine output: 5 to 7 days (mL/min)
243Mean Difference (IV, Random, 95% CI)0.23 [0.09, 0.37]

 2 Creatinine clearance4Mean Difference (IV, Random, 95% CI)Subtotals only

    2.1 24 hours (mL/min)
383Mean Difference (IV, Random, 95% CI)-2.84 [-14.07, 8.39]

    2.2 2 to 4 days (mL/min)
374Mean Difference (IV, Random, 95% CI)0.42 [-16.68, 17.52]

    2.3 5 to 7 days (mL/min)
243Mean Difference (IV, Random, 95% CI)0.58 [-16.43, 17.60]

 
Comparison 12. Studies on participants with pre-existing renal impairment

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality10959Peto Odds Ratio (Peto, Fixed, 95% CI)0.74 [0.36, 1.52]

 2 Acute renal injury11979Peto Odds Ratio (Peto, Fixed, 95% CI)0.40 [0.22, 0.76]

 3 Urine output4707Mean Difference (IV, Random, 95% CI)0.35 [-0.16, 0.85]

    3.1 Urine output, 24 hours
4416Mean Difference (IV, Random, 95% CI)0.35 [-0.12, 0.81]

    3.2 Urine output, 2 to 3 days
2291Mean Difference (IV, Random, 95% CI)0.43 [-0.78, 1.65]

 4 Creatinine clearance4646Mean Difference (IV, Random, 95% CI)10.65 [0.04, 21.27]

    4.1 Creatinine clearance, 24 hours
4347Mean Difference (IV, Random, 95% CI)7.78 [-10.39, 25.94]

    4.2 Creatinine clearance, 2 to 3 days
3299Mean Difference (IV, Random, 95% CI)14.16 [-6.20, 34.52]

 
Comparison 13. Studies with low risk of bias: sensitivity analysis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Reported mortality, low risk of bias studies only191604Peto Odds Ratio (Peto, Fixed, 95% CI)1.01 [0.52, 1.97]

 2 Acute renal injury, requiring dialysis, low risk of bias studies only161550Peto Odds Ratio (Peto, Fixed, 95% CI)1.05 [0.55, 2.03]

 3 Urine output at 24 hours, low risk of bias studies only11798Mean Difference (IV, Random, 95% CI)0.20 [-0.04, 0.44]

 4 Creatinine clearance at 24 hours, low risk of bias studies only9817Mean Difference (IV, Random, 95% CI)6.59 [-3.53, 16.72]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Appendix 1. Search strategies employed

Search strategy for MEDLINE (Ovid SP)
1 exp Kidney Failure/ or exp Kidney Failure Acute/ or exp Kidney Failure Chronic/ or exp Kidney Function Tests/ or exp Glomerular Filtration Rate/ or exp Renal Circulation/ or exp Renal Plasma Flow/ or exp Renal Insufficiency/ or kidney.ti,ab. or (glomerul* adj3 filtration).mp. or (renal adj3 (failure or protect* or function*)).mp. or kidney function test*.mp. or renal function test*.mp. or free water clearance.mp. or fractional excretion of sodium.mp. or (urine adj3 (output or flow)).mp.
2 exp Angiotensin Converting Enzyme Inhibitors/ or exp Fluid Therapy/ or exp Infusions Intravenous/ or exp Angiotensin Converting Enzyme Inhibitors/ or exp diuretics/ or exp mannitol/ or exp Furosemide/ or exp Dopamine/ or exp Dopamine Agonists/ or (diuretic* or mannitol or frusemide or furosemide).mp. or (fluid* adj3 therap*).mp. or (intravenous adj3 fluid*).mp. or hydration.ti,ab. or angiotensin converting enzyme inhibitor*.mp. or ACE inhibitor*.mp. or dopamin*.ti,ab.
3 exp Perioperative Care/ or exp Intraoperative Period/ or exp Intraoperative Care/ or exp Intraoperative Complications/ or (peri?operativ* or intra?operativ*).ti,ab.
4 1 and 2 and 3
5 reno?protect*.af.
6 4 or 5 (2513)
7 ((randomized controlled trial or controlled clinical trial).pt. or randomized.ab. or placebo.ab. or clinical trials as topic.sh. or randomly.ab. or trial.ti.) not (animals not (humans and animals)).sh.
8 6 and 7

Search strategy for EMBASE (Ovid SP)

1 exp kidney failure/ or exp kidney failure/ or exp kidney function test/ or exp glomerulus filtration rate/ or exp kidney circulation/ or exp kidney clearance/ or exp kidney plasma flow/ or exp urine flow rate/ or exp urine volume/ or kidney.ti,ab. or (glomerul* adj3 filtration).mp. or (renal adj3 (failure or protect* or function*)).mp. or kidney function test*.mp. or renal function test*.mp. or free water clearance.mp. or fractional excretion of sodium.mp. or (urine adj3 (output or flow)).mp.
2 exp dipeptidyl carboxypeptidase inhibitor/ or exp fluid therapy/ or intravenous drug administration/ or exp diuretic agent/ or exp diuretic agent/ or exp mannitol/ or exp furosemide/ or exp dopamine/ or exp dopamine receptor stimulating agent/ or (diuretic* or mannitol or frusemide or furosemide).mp. or (fluid* adj3 therap*).mp. or (intravenous adj3 fluid*).mp. or hydration.ti,ab. or angiotensin converting enzyme inhibitor*.mp. or ACE inhibitor*.mp. or dopamin*.ti,ab.
3 exp perioperative period/ or exp intraoperative period/ or exp peroperative care/ or (peri?operativ* or intra?operativ*).ti,ab.
4 1 and 2 and 3
5 reno?protect*.ti,ab.
6 4 or 5
7 (placebo.sh. or controlled study.ab. or random*.ti,ab. or trial*.ti,ab. or ((singl* or doubl* or trebl* or tripl*) adj3 (blind* or mask*)).ti,ab.) not (animals not (humans and animals)).sh.
8 6 and 7

Search strategy for CENTRAL, The Cochrane Library

#1 MeSH descriptor Acute Kidney Injury explode all trees
#2 MeSH descriptor Kidney Failure, Chronic explode all trees
#3 MeSH descriptor Kidney Function Tests explode all trees
#4 MeSH descriptor Glomerular Filtration Rate explode all trees
#5 MeSH descriptor Renal Circulation explode all trees
#6 MeSH descriptor Renal Plasma Flow, Effective explode all trees
#7 MeSH descriptor Renal Insufficiency explode all trees
#8 kidney
#9 glomerul* near filtration
#10 renal near (failure or protect* or function*)
#11 kidney function test*
#12 renal function test*
#13 free water clearance
#14 (fractional excretion) of sodium
#15 urine near (output or flow)
#16 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15)
#17 MeSH descriptor Angiotensin-Converting Enzyme Inhibitors explode all trees
#18 diuretic* or mannitol or frusemide or furosemide
#19 MeSH descriptor Fluid Therapy explode all trees
#20 fluid* near therap*
#21 MeSH descriptor Infusions, Intravenous explode all trees
#22 (intravenous near fluid*) or hydration
#23 angiotensin converting enzyme inhibitor*
#24 ACE inhibitor*
#25 MeSH descriptor Diuretics explode all trees
#26 MeSH descriptor Mannitol explode all trees
#27 MeSH descriptor Furosemide explode all trees
#28 MeSH descriptor Dopamine explode all trees
#29 MeSH descriptor Dopamine Agonists explode all trees
#30 dopamin*
#31 (#16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30)
#32 MeSH descriptor Perioperative Care explode all trees
#33 MeSH descriptor Intraoperative Care explode all trees
#34 MeSH descriptor Intraoperative Complications explode all trees
#35 MeSH descriptor Intraoperative Period explode all trees
#36 perioperativ* or intraoperativ*
#37 (#32 OR #33 OR #34 OR #35 OR #36)
#38 (#16 AND #31 AND #37)

 

Appendix 2. data extraction form

Data extraction form

Study ID:                                 

Language: English/

What was the surgical procedure? 

What was the study intervention?

How many participants were studied?

How many in the intervention group?

How many in the control group?

Were the inclusion criteria clearly defined?

Were the exclusion criteria clearly defined?

Age group         Intervention                   Control

Male:Female numbers:

Bias:

Was there randomization of allocation in the groups?

Was there adequate information about randomization?

Was there allocation concealment?

Was the allocation concealment adequate?

Were there any withdrawals from the study?

How many people withdrew from each group?

Was there blinding in the study?

Study details:

What was the actual nature of the intervention?

When did the intervention start and finish?

What was the actual nature of the control group?

When did the control group start and finish?

Were the two groups treated equally?

What were the outcomes studied?

Mortality

Acute renal failure

Urine output

Creatinine clearance

Free water clearance

Fractional excretion of sodium

Renal blood flow

Urinary microalbumin:creatinine ratio

Urinary NAG:creatinine ratio

Urinary RBOP:creatinine ratio

Urinary NGAL:creatinine ratio

Plasma cystatin C

When were the outcomes measured?

Preoperative    Postoperative: 24 hours       Postoperative: 48 hours       Postoperative: 72 hours       Postoperative: day (note)

Was the outcome assessment blinded?

Was there intention-to-treat analysis?

Are mean and standard deviation given?

Other measures of presentation of data

Graphic data?

Results:

Mean and SD    Other measures: (please specify clearly)

Remarks:

Drug company sponsorship?

Other comments:

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

Last assessed as up-to-date: 11 August 2012.


DateEventDescription

9 September 2013New citation required but conclusions have not changedWe updated the search until August 2012; some of the authors have been changed from the previous version of this review (Zacharias 2008)

We included 19 new studies

We identified new interventions and incorporated them into the review (N-acetyl cysteine; atrial natriuretic peptide; erythropoietin (EPO))

We identified new outcomes in the form of biomarkers of renal damage and added them to the review in keeping with current trends in the literature

The conclusions of the new update have not changed from those provided in the previous published version of this review (Zacharias 2008)

9 September 2013New search has been performedMajor update completed



 

History

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

Protocol first published: Issue 2, 2002
Review first published: Issue 3, 2005


DateEventDescription

7 August 2008New search has been performedThe following changes from the previous published review are made in this updated review.

1.We have modified the search strategy and updated it until June 2007.
2. A change in members of the review team from the first published review to the present update. Some of the original review authors were no longer available, and other authors have joined the review team.
3. Modifed search strategy in June 2007 identified further studies, which are incorporated in the updated review.
4. Some of the previous studies included in the review have been dropped following further detailed evaluation of the studies and new ones were added.
5. There are minor changes in the results following the above modifications, but the conclusions remain the same.

7 August 2008New citation required but conclusions have not changedNew review team; review has undergone substantial work



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

Dr Mathew Zacharias
Contact reviewer. Involved in development of the protocol, the search strategy, retrieval of the papers, screening of the papers, data extraction and data input and writing of the protocol and review, including the updated review

Dr Mohan Mugawar
Screening of the papers, extraction of data, checking of data input and writing of the updated review

Prof G Peter Herbison
Statistical and general advice, checking of the review

Dr Palvannan Sivalingam
Co-reviewer. Involved with development of the protocol and screening of the papers, data extraction, checking of data input and checking of the review, including the update

Prof Robert J Walker
Specialist advice on kidney and renal function tests

Dr Karen Hovhannisyan
Development of new search strategy and performing the search

Dr Niamh P Conlon
Co-reviewer for the previous version of the review; special advisor on the review

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

Mathew Zacharias: none known

Mohan Mugawar: none known

G Peter Herbison: none known

Robert J Walker: none known

Karen Hovhannisyan: none known

Palvannan Sivalingam: none known

Niamh P Conlon: none known

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms
 

Internal sources

  • Dunedin Hospital & Dunedin School of Medicine, Dunedin, New Zealand.

 

External sources

  • None, New Zealand.

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

We have included new interventions in this review (N-acetyl cysteine, atrial natriuretic peptide, sodium bicarbonate, antioxidants and erythropoietin). We have looked at some of the newer biomarkers of kidney damage (urinary NAG/creatinine ratio; urinary RBP/creatinine ratio; plasma cystatin C; urinary NGAL/creatinine ratio) as surrogate markers for renal damage.

 

Notes

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Notes
  19. Index terms

This review was published first in 2005 and was updated in 2008 (Zacharias 2005; Zacharias 2008).

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé scientifique
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. References to studies awaiting assessment
  24. Additional references
  25. References to other published versions of this review
Adabag 2008 {published data only}
  • Adabag AS, Ishani A, Koneswaran S, Johnson DJ, Kelly RF, Ward HB, et al. Utility of N-acetylcysteine to prevent acute kidney injury after cardiac surgery: a randomized controlled trial. American Heart Journal 2008;155:1143-9. [PUBMED: PMID: 18513531]
Amano 1994 {published data only}
  • Amano J, Suzuki A, Sunamori M. Salutary effect of reduced glutathione on renal function in coronary artery bypass operation. Journal of the American College of Surgeons 1994;179:714-20. [MEDLINE: 7952483]
Amano 1995 {published data only}
Ascione 1999 {published data only}
Barr 2008 {published data only}
  • Barr LF, Kolodner K. N-acetylcysteine and fenoldopam protect the renal function of patients with chronic renal insufficiency undergoing cardiac surgery. Critical Care Medicine 2008;36(5):1427-35. [PUBMED: PMID: 18434903 ]
Berendes 1997 {published data only}
  • Berendes E, Mollhoff T, van Aken H, Schmidt C, Erren M, Deng MC, et al. Effects of dopexamine on creatinine clearance, systemic inflammation, and splanchnic oxygenation in patients undergoing coronary artery bypass grafting. Anesthesia and Analgesia 1997;84:950-7. [MEDLINE: 9141914]
Bergman 2002 {published data only}
  • Bergman AS, Odar-Cederlof I, Westman L, Bjellerup P, Hoglund P, Ohqvist G. Diltiazem infusion for renal protection in cardiac surgical patients with preexisting renal dysfunction. Journal of Cardiothoracic and Vascular Anesthesia 2002;16(3):294-9. [MEDLINE: 12073199]
Burns 2005 {published data only}
Carcoana 2003 {published data only}
  • Carcoana OV, Mathew JP, Davis E, Byrne DW, Hayslett JP, Hines RL, et al. Mannitol and dopamine in patients undergoing cardiopulmonary bypass: a randomized clinical trial. Anesthesia and Analgesia 2003;97:1222-9. [MEDLINE: 14570627]
Chen 2007 {published data only}
  • Chen HH, Sundt TM, Cook DJ, Heublein DM, Burnett JC. Low dose nesiritide and the preservation of renal function in patients with renal dysfunction undergoing cardio-pulmonary-bypass surgery. Circulation 2007;116(11 Suppl):1134-8. [PUBMED: PMID: 17846293]
Cho 2009 {published data only}
  • Cho JE, Shim JK, Chang JH, Oh YJ, Kil HK, Rha KH, et al. Effect of nicardipine on renal function after robot-assisted laparoscopic radical prostatectomy. Urology 2009;73:1056-60. [PUBMED: PMID: 19394503]
Cogliati 2007 {published data only}
  • Cogliati AA, Vellutini R, Nardini A, Urovi S, Hamdan M, Landoni G, et al. Fenoldopam infusion for renal protection in high-risk cardiac surgery patients: a randomized clinical study. Journal of Cardiothoracic and Vascular Anesthesia 2007;21(6):847-50. [PUBMED: PMID: 18068064]
Colson 1990 {published data only}
  • Colson P, Ribstein J, Mimran A, Grolleau D, Chaptal PA, Roquefeuil B. Effect of angiotensin converting enzyme inhibition on blood pressure and renal function during open heart surgery. Anesthesiology 1990;72:23-7. [MEDLINE: 2404429]
Colson 1992 {published data only}
Costa 1990 {published data only}
  • Costa P, Ottino GM, Matani A, Pansini S, Canavese C, Passerini G, et al. Low-dose dopamine during cardiopulmonary bypass in patients with renal dysfunction. Journal of Cardiothoracic Anesthesia 1990;4:469-73. [MEDLINE: 2132343]
Cregg 1999 {published data only}
Dawidson 1991 {published data only}
  • Dawidson IJ, Willms CD, Sandor ZF, Coorpender LL, Reisch JS, Fry WJ. Ringer's lactate with or without 3% dextran-60 as volume expanders during abdominal aortic surgery. Critical Care Medicine 1991;19:36-42. [MEDLINE: 1702696]
Dehne 2001 {published data only}
de Lasson 1995 {published data only}
  • de Lasson L, Hansen HE, Juhl B, Paaske WP, Pedersen EB. A randomized, clinical study of the effect of low-dose dopamine on cental and renal haemodynamics in infrarenal aortic surgery. European Journal of Endovascular Surgery 1995;10:82-90. [MEDLINE: 7633974]
de Lasson 1997 {published data only}
  • de Lasson L, Hansen HE, Juhl B, Paaske WP, Pedersen EB. Effect of felodipine on renal function and vasoactive hormones in infrarenal aortic surgery. British Journal of Anaesthesia 1997;79:719-25. [MEDLINE: 9496202]
Donmez 1998 {published data only}
  • Donmez A, Ergun F, Kayhan Z, Tasdelen A, Dogan S. Verapamil and nimodipine do not improve renal function during cardiopulmonary bypass. Acta Anesthesiologica Italica 1998;49:173-7.
Dural 2000 {published data only}
  • Dural O, Ozkara A, Celebioglu B, Kanbak M, Ciliv G, Aypar U. Comparative study of dopamine and mannitol effects on renal function during cardiopulmonary bypass by using N-acetyl-beta-D-glucosaminidase assay. Turkish Journal of Medical Science 2000;30:453-7.
Durmaz 2003 {published data only}
  • Durmaz I, Yagdi T, Calkavur T, Mahmudov R, Apaydin AZ, Posacioglu H, et al. Prophylactic dialysis in patients with renal dysfunction undergoing on-pump coronary artery bypass surgery. Annals of Thoracic Surgery 2003;75:859-64. [MEDLINE: 12645707]
Fischer 2005 {published data only}
Gubern 1988 {published data only}
  • Gubern JM, Sancho JJ, Simo J, Sitges-Serra A. A randomized trial on the effect of mannitol on postoperative renal function in patients with obstructive jaundice. Surgery 1988;103:39-44. [MEDLINE: 3122349]
Haase 2007 {published data only}
  • Haase M, Haase-Fielitz A, Bagshaw SM, Reade MC, Morgera S, Seevenayagam S, et al. Phase ll, randomized, controlled trial of high-dose N-acetylcysteine in high-risk cardiac surgery patients. Critical Care Medicine 2007;35(5):1324-31. [PUBMED: PMID: 17414730]
Haase 2009 {published data only}
  • Haase M, Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, et al. Sodium bicarbonate to prevent increases in serum creatinine after cardiac surgery: a pilot double-blind, randomized controlled trial. Critical Care Medicine 2009;37(1):39-47. [PUBMED: PMID: 19112278]
Halpenny 2002 {published data only}
  • Halpenny M, Rushe C, Breen P, Cunningham AJ, Boucher-Hayes D, Shorten GD. The effect of fenoldopam on renal function in patients undergoing elective aortic surgery. European Journal of Anaesthesiology 2002;19(1):32-9. [MEDLINE: 11913801]
Harten 2008 {published data only}
  • Harten J, Crozier JEM, McCreath B, Hay A, McMillan DC, McArdle CS, et al. Effect of intraoperative fluid optimization on renal function in patients undergoing emergency abdominal surgery: a randomized controlled pilot study. International Journal of Surgery 2008;6(3):197-204. [PUBMED: PMID: 18424200]
Hynninen 2006 {published data only}
  • Hynninen MS, Niemi TT, Poyhia R, Raininko EI, Salmenpera MT, Lepantalo MJ, et al. N-acetylcysteine for the prevention of kidney injury in abdominal aortic surgery: a randomized, double-blind, placebo-controlled trial. Anesthesia and Analgesia 2006;102:1638-45. [PUBMED: PMID: 16717300]
Kaya 2007 {published data only}
  • Kaya K, Oguz M, Akar AR, Durdu S, Aslan A, Erturk S, et al. The effect of sodium nitroprusside infusion on renal function during reperfusion period in patients undergoing coronary artery bypass grafting: a prospective randomized clinical trial. European Journal of Cardiothoracic Surgery 2007;31:290-7. [PUBMED: PMID: 17174559]
Kleinschmidt 1997 {published data only}
  • Kleinschmidt Von S, Bauer M, Grundmann U, Schneider A, Wagmer B, Graeter T. Influence of gamma-hydroxybutyrate and pentoxifylline on renal function markers in coronary artery bypass graft surgery. Anaesthesiologie Reanimation (German) 1997;22(4):102-7. [MEDLINE: 9376042]
Kramer 2002 {published data only}
  • Kramer BK, Preuner J, Ebenburger A, Kaiser M, Bergner U, Eilles C, et al. Lack of renoprotective effect of theophylline during aortocoronary bypass surgery. Nephrology, Dialysis and Transplantation 2002;17:910-5. [MEDLINE: 11981083]
Kulka 1996 {published data only}
  • Kulka PJ, Tryba M, Zenz M. Preoperative alpha2-adrenergic receptor agonists prevent the deterioration of renal function after cardiac surgery: results of a randomized, controlled trial. Critical Care Medicine 1996;24:947-52. [MEDLINE: 8681596]
Lassnigg 2000 {published data only}
  • Lassnigg A, Donner E, Grubhofer G, Presterl E, Drubl W, Hiesmayr M. Lack of renoprotective effects of dopamine and furosemide during cardiac surgery. Journal of American Society of Nephrology 2000;11:97-104. [MEDLINE: 10616845]
Lau 2001 {published data only}
  • Lau LL, Halliday MI, Smye MG, Lee B, Hannon RJ, Gardiner KR, et al. Extraperitoneal approach reduces intestinal and renal dysfunction in elective abdominal aortic aneurysm repair. International Angiology 2001;20(4):282-7. [MEDLINE: 11782693]
Licker 1996 {published data only}
  • Licker M, Bednarkiewicz M, Neidhart P, Pretre R, Montessuit M, Favre H, et al. Preoperative inhibition of angiotensin-converting enzyme improves systemic and renal haemodynamic changes during aortic abdominal surgery. British Journal of Anaesthesia 1996;76:632-9. [MEDLINE: 12456411]
Loef 2004 {published data only}
  • Loef BG, Henning RH, Epema AH, Rietman GW, van Oeveren W, Navis GJ, et al. Effect of dexamethasone on perioperative renal function impairment during cardiac surgery with cardiopulmonary bypass. British Journal of Anaesthesia 2004;93(6):793-8. [MEDLINE: 15563558]
Marathias 2006 {published data only}
Mitaka 2008 {published data only}
  • Mitaka C, Kudo T, Jibiki M, Sugano N, Inoue Y, Makita K, et al. Effects of human atrial natriuretic peptide on renal function in patients undergoing abdominal aortic aneurysm repair. Critical Care Medicine 2008;36(3):745-51. [PUBMED: PMID: 18431264]
Morariu 2005 {published data only}
  • Morariu AM, Loaf BG, Aarts LPHJ, Rietman GW, Bakhorst G, van Oeveren W, et al. Dexamethasone: benefits and prejudice for patients undergoing on-pump coronary artery bypass grafting. A study on myocardial, pulmonary, renal, intestinal and hepatic injury. Chest 2005;128(4):2677-86. [MEDLINE: 16236942]
Morgera 2002 {published data only}
Myles 1993 {published data only}
  • Myles PS, Buckland MR, Schenk NJ, Cannon GB, Langley M, Davis BB, et al. Effect of renal dose dopamine on renal function following cardiac surgery. Anaesthesia and Intensive Care 1993;21:56-61. [MEDLINE: 8447608]
Nicholson 1996 {published data only}
Nouri-Majalan 2009 {published data only}
  • Nouri-Majalan N, Ardakani EF, Forouzannia K, Moshtaghian H. Effect of allopurinol and vitamin E on renal function in patients with coronary artery bypass grafts. Vascular Health and Risk Management 2009;5:489-94. [PUBMED: PMID: 19554089 ]
O'Hara 2002 {published data only}
Parks 1994 {published data only}
Perez 2002 {published data only}
Prasad 2010 {published data only}
  • Prasad A, Banakal S, Muralidhar K. N-acetylcysteine does not prevent renal dysfunction after off-pump coronary artery bypass surgery. European Journal of Anaesthesiology 2010;27:973-7. [PUBMED: PMID: 20299984]
Prowle 2012 {published data only}
Pull Ter Gunne 1990 {published data only}
  • Pull Ter Gunne AJ, Bruining HA, Obertop H. Haemodynamics and 'optimal' hydration in aortic cross clamping. The Netherlands Journal of Surgery 1990;42:113-7.
Ristikankare 2006 {published data only}
  • Ristikankare A, Kuitunen T, Kuitunen A, Uotila L, Vento A, Suojaranta-Ylinen R, et al. Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery. British Journal of Anaesthesia 2006;97(5):611-6. [MEDLINE: 16914459]
Ryckwaert 2001 {published data only}
  • Ryckwaert F, Colson P, Ribstein J, Boccara G, Guillon G. Haemodynamic and renal effects of intravenous enalapril during coronary artery bypass graft surgery in patients with ischaemic heart dysfunction. British Journal of Anaesthesia 2001;86:169-75. [MEDLINE: 11573655]
Sezai 2000 {published data only}
Sezai 2009 {published data only}
  • Sezai A, Hata M, Niino T, Yoshitake I, Unosawa S, Wakui S, et al. Influence of continuous infusion of low-dose human atrial natriuretic peptide on renal function during cardiac surgery. Journal of the American College of Cardiology 2009;54(12):1058-64. [PUBMED: PMID: 19744614]
Sezai 2011 {published data only}
  • Sezai A, Hata M, Niino T, Yoshitake I, Unosawa S, Wakui S, et al. Results of low dose human atrial natriuretic peptide infusion in nondialysis patients with chronic kidney disease undergoing coronary artery bypass grafting. Journal of the American College of Cardiology 2011;58(9):897-903. [PUBMED: PMID: 21851876]
Shackford 1983 {published data only}
  • Shackford SR, Sise MJ, Friedlund PH, Rowley WR, Peters RM, Virgilio RW, et al. Hypertonic sodium lactate versus lactated Ringer's solution for intravenous fluid therapy in operations on the abdominal aorta. Surgery 1983;94:41-51. [MEDLINE: 6857511]
Shim 2007 {published data only}
  • Shim JK, Choi SH, Oh YJ, Kim CS, Yoo KJ, Kwak YL. The effect of mannitol on oxygenation and creatinine kinase MB release in patients undergoing multivessel off-pump coronary artery bypass surgery. The Journal of Thoracic and Cardiovascular Surgery 2007;133(3):704-9. [MEDLINE: 17320568]
Song 2009 {published data only}
  • Song YR, Lee T, You SJ, Chin HJ, Chae D-W, Lim C, et al. Prevention of acute kidney injury by erythropoietin in patients undergoing coronary artery bypass grafting: a pilot study. American Journal of Nephrology 2009;30:253-60. [PUBMED: PMID: 19494484]
Tang 1999 {published data only}
  • Tang AT, El-Gamel A, Keevil B, Yonan N, Deiraniya AK. The effect of renal dose dopamine on renal tubular function following cardiac surgery: assessed by measuring retinol binding protein (RBP). European Journal of Cardiothoracic Surgery 1999;15:717-22. [MEDLINE: 10386423]
Tang 2002 {published data only}
  • Tang AT, Knott J, Nanson J, Hsu J, Haw MP, Ohri SK. A prospective randomized study to evaluate the renoprotective action of beating heart coronary surgery in low risk patients. European Journal of Cardiothoracic Surgery 2002;22:118-23. [MEDLINE: 12103384]
Thompson 1986 {published data only}
Turner 2008 {published data only}
Urzua 1992 {published data only}
  • Urzua J, Troncoso S, Bugedo G, Canessa R, Munoz H, Lema G, et al. Renal function and cardiopulmonary bypass: effect of perfusion pressure. Journal of Cardiothoracic and Vascular Anesthesia 1992;6(3):299-303. [MEDLINE: 1610995]
Wahbah 2000 {published data only}
  • Wahbah AM, el-Hefny MO, Wafa EM, el-Kharbotly W, el-Enin AA, Zaglol A, et al. Perioperative renal protection in patients with obstructive jaundice using drug combinations. Hepatogastroenterology 2000;47:1691-4. [MEDLINE: 11149033]
Welch 1995 {published data only}
Wijnen 2002 {published data only}
  • Wijnen MH, Vader HL, Van Den Wall Bake AW, Roumen RM. Can renal dysfunction after infra-renal aortic aneurysm repair be modified by multi-antioxidant supplementation?. Journal of Cardiovascular Surgery 2002;43:483-8. [MEDLINE: 12124559]
Witczak 2008 {published data only}
  • Witczak BJ, Hartmann A, Geiran OR, Bugge JF. Renal function after cardiopulmonary bypass surgery in patients with impaired renal function. A randomized study of the effect of nifedipine. European Journal of Anaesthesiology 2008;25:319-25. [PUBMED: PMID: 18182121]
Woo 2002 {published data only}
  • Woo EB, Tang AT, el-Gamel A, Keevil B, Greenhalgh D, Patrick M, et al. Dopamine therapy for patients at risk of renal dysfunction following cardiac surgery: science or fiction?. European Journal of Cardiothoracic Surgery 2002;22:106-11. [MEDLINE: 12103352]
Yavuz 2002A {published data only}
  • Yavuz S, Ayabaken N, Dilek K, Ozdemir A. Renal dose of dopamine in open heart surgery; does it protect renal tubular function?. Journal of Cardiovascular Surgery 2002;43:25-30. [MEDLINE: 11803323]
Yavuz 2002B {published data only}
  • Yavuz S, Ayabakan N, Goncu MT, Ozdemir A. Effect of combined dopamine and diltiazem on renal function after cardiac surgery. Medical Science Monitor 2002;8:145-50. [MEDLINE: 12011785]
Zanardo 1993 {published data only}
  • Zanardo G, Michielon P, Rosi P, Teodori T, Antonucci F, Caenaro G, et al. Effect of a continuous diltiazem infusion on renal function during cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia 1993;7(6):711-6. [MEDLINE: 8305662]

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé scientifique
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. References to studies awaiting assessment
  24. Additional references
  25. References to other published versions of this review
Abe 1993 {published data only}
Aho 2004 {published data only}
  • Aho PS, Niemi T, Lindgren L, Lepantalo M. Endovascular vs open AAA repair: similar effects on renal proximal tubular function. Scandinavian Journal of Surgery 2004;93:52-6. [MEDLINE: 15116821]
Amar 2001 {published data only}
Antonucci 1996 {published data only}
  • Antonucci F, Calo L, Rizzolo M, Cantaro S, Bertoliswsi M, Travaglini M, et al. Nifedipine can preserve renal function in patients undergoing aortic surgery with infrarenal crossclamping. Nephron 1996;74(4):668-73. [MEDLINE: 8956299]
Baldwin 1994 {published data only}
Boldt 2000 {published data only}
  • Boldt J, Lehmann A, Rompert R, Haisch G, Isgro F. Volume therapy with a new hydroxyethyl starch solution in cardiac surgical patients before cardiopulmonary bypass. Journal of Cardiothoracic and Vascular Anesthesia 2000;14:264-8. [MEDLINE: 10890478]
Boldt 2006 {published data only}
  • Boldt J, Scholhorn T, Mayer J, Piper S, Suttner S. The value of albumin-based intravascular volume replacement strategy in elderly patients undergoing major abdominal surgery. Anesthesia and Analgesia 2006;103(1):191-9. [MEDLINE: 16790652]
Boodhwani 2009 {published data only}
  • Boodhwani M, Rubens FD, Wozny D, Nathan HJ. Effects of mild hypothermia and rewarming on renal function after coronary artery bypass grafting. Annals of Thoracic Surgery 2009;87:489-95. [PUBMED: PMID: 19161766]
Boutros 1979 {published data only}
  • Boutros AR, Ruess R, Olson L, Hoyt JL, Baker WH. Comparison of hemodynamic, pulmonary, and renal effects of use of three types of fluids after major surgical procedures on the abdominal aorta. Critical Care Medicine 1979;7(1):9-13. [MEDLINE: 367709]
Bove 2005 {published data only}
  • Bove T, Lanjdoni G, Calabro MG, Aletti G, Marino G, Cerchierini E, et al. Renoprotective action of fenoldopam in high-risk patients undergoing cardiac surgery: a prospective, double-blind, randomized clinical trial. Circulation 2005;111(24):3230-5. [MEDLINE: 15967861]
Caglikulekci 1998 {published data only}
  • Caglikulekciaz S, Yilmaz S, Kayaalp C, Demirbag A, Akoglu M. Postoperative renal function in obstructive jaundice and the effect of dopamine, mannitol and lactulose: a prospective clinical study. The Turkish Journal of Surgery 1998;14(4):230-6.
Cahill 1987 {published data only}
Caimmi 2003 {published data only}
  • Caimmi PP, Pagani L, Micalizzi E, Fiume C, Guani S, Bernardi M, et al. Fenoldopam for renal protection in patients undergoing cardiopulmonary bypass. Journal of Cardiothoracic and Vascular Anesthesia 2003;17(4):491-4. [MEDLINE: 12968238]
Christakis 1992 {published data only}
Christenson 1995 {published data only}
  • Christenson JT, Maurice F, Simonet V, Velebit V, Schmuziger M. Normothermic versus hypothermic perfusion during primary coronary artery bypass grafting. Cardiovascular Surgery 1995;3(5):519-24. [MEDLINE: 8574537]
Dementi'eva 1996 {published data only}
  • Dementi'eva II, Charnaia MA, Dzemeshkevich SL, Ziuliaeva TP. The preventive role of large doses of aprotinin in decreasing the degree of metabolic disorders during aortocoronary bypass operations. Anestheziologiia i Reanimatologica (Russian) 1996;1:55-8. [MEDLINE: 8686945]
Feindt 1995 {published data only}
  • Feindt PR, Walcher S, Volkmer I, Keller HE, Straub U, Hewer H, Seyfert UT, et al. Effect of high-dose aprotinin on renal function in aortocoronary bypass grafting. Annals of Thoracic Surgery 1995;60:1076-80. [MEDLINE: 7574952]
Fischer 2002 {published data only}
Fisher 1998 {published data only}
Franklin 1997 {published data only}
  • Franklin SC, Moulton M, Sicard GA, Hammerman MR, Miller SB. Insulin-like growth factor I preserves renal function postoperatively. American Journal of Physiology: Renal, Fluid and Electrolyte Physiology 1997;272(241-2):F257-9. [MEDLINE: 9124404]
Frumento 2006 {published data only}
  • Frumento RJ, Logginidou HG, Wahlqander S, Wagener G, Playford HR, Sladen RN. Dexmedetomidine infusion is associated with enhanced renal function after thoracic surgery. Journal of Clinical Anesthesia 2006;18:422-6. [MEDLINE: 16980158]
Garwood 2003 {published data only}
  • Garwood S, Swamidoss CP, Davis EA, Samson L, Hines RL. A case series of low dose fenoldopam in seventy cardiac surgical patients at increased risk of renal dysfunction. Journal of Cardiothoracic and Vascular Anesthesia 2003;17(1):17-21. [MEDLINE: 12635055]
Gatot 2004 {published data only}
Gerola 2004 {published data only}
  • Gerola LR, Buffolo E, Jasbik W, Botelho B, Bosco J, Brasil LA, et al. Off-pump versus on-pump myocardial revascularization in low-risk patients with one or two vessel disease: perioperative results in a multicenter randomized controlled trial. Annals of Thoracic Surgery 2004;77:569-73. [MEDLINE: 14759439]
Gilbert 2001 {published data only}
  • Gilbert TB, Hasnain JU, Flinn WR, Benjamin ME. Fenoldopam infusion associated with preserving renal function after aortic cross-clamping for aneurysm repair. Journal of Cardiovascular Pharmacology and Therapeutics 2001;6:31-6. [MEDLINE: 11452334]
Godet 2008 {published data only}
  • Godet G, Lehot J-J, Janvier G, Steib A, De Castro V, Coriat P. Safety of HES 130/0.4 (Voluven) in patients with preoperative renal dysfunction undergoing abdominal aortic surgery: a prospective randomized controlled parallel-group multicentre trial. European Journal of Anaesthesiology 2008;25:986-94. [PUBMED: PMID: 18492315]
Goto 1992 {published data only}
Grundmann 1985 {published data only}
Halpenny 2001 {published data only}
Hayashida 1997 {published data only}
  • Hayashida M, Hanaoka K, Shimada Y, Namiki A, Amaha K. The effect of low-dose prostglandin E1 on intra- and post-operative renal function. The Japanese Journal of Anesthesiology 1997;46(4):464-70. [MEDLINE: 9128016]
Hayashida 2000 {published data only}
Hisatomi 2012 {published data only}
  • Hisatomi K, Eishi K. Multicenter trial of carperitide in patients with renal dysfunction undergoing cardiovascular surgery. General Thoracic Cardiovascular Surgery 2012;60:21-30. [PUBMED: PMID: 22237735]
Izumi 2006 {published data only}
Izumi 2008 {published data only}
  • Izumi K, Eishi K, Yamachika S, Hashizume K, Miura T, Nakaji S. The efficacy of human atrial natriuretic peptide in patients with renal dysfunction undergoing cardiac surgery. Annals of Thoracic and Cardiovascular Surgery 2008;14(5):294-302. [PUBMED: PMID: 18989245 ]
Junnarkar 2003 {published data only}
  • Junnerkar S, Lau LL, Edrees WK, Underwood D, Smye MG, Lee B, et al. Cytokine activation and intestinal mucosal and renal dysfunction are reduced in endovascular AAA repair compared to surgery. Journal of Endovascular Therapy 2003;10:195-202. [MEDLINE: 12877599]
Kulka 1993 {published data only}
  • Kulka PJ, Tryba M, Menzel C, Leurs F, Frankenberg C. Preoperative clonidine improves postoperative renal function in CABG patients. British Journal of Anaesthesia 1993;70:74.
Kumle 1999 {published data only}
Kunt 2009 {published data only}
  • Kunt AT, Akgun S, Atalan N, Bitir N, Arsan S. Frusamide infusion prevents the requirement of renal replacement therapy after cardiac surgery. The Anatolian Journal of Cardiology 2009;9(6):499-504. [PUBMED: PMID: 19965324 ]
Kuraoka 1995 {published data only}
  • Kuraoka S, Orita H, Watanabe T, Abe K, Abe H, Inui S, et al. Effect of combined aprotinin and prostaglandin E1 therapy on aortic arch replacement. The Japanese Journal of Thoracic Surgery 1995;48(3):198-201. [MEDLINE: 7534838]
Lema 1995 {published data only}
  • Lema G, Meneses G, Urzua J, Jalil R, Canessa R, Moran S, et al. Effects of extracorporeal circulation on renal function in coronary surgical patients. Anesthesia and Analgesia 1995;81:446-51. [MEDLINE: 7653802]
Lema 1998 {published data only}
  • Lema G, Urzua J, Jalil R, Canessa R, Moran S, Sacco C, et al. Renal protection in patients undergoing cardiopulmonary bypass with preoperative abnormal renal function. Anesthesia and Analgesia 1998;86(1):3-8. [MEDLINE: 9428842]
Lemmer 1996 {published data only}
  • Lemmer JH Jr, Dilling EW, Morton JR, Rich JB, Robicsek F, Bricker DL, et al. Aprotinin for primary coronary artery bypass grafting: a multicenter trial of three dose regimens. Annals of Thoracic Surgery 1996;62:1659-68. [MEDLINE: 8957369]
Levy 1995 {published data only}
  • Levy JH, Pifarre R, Schaff HV, Horrow JC, Albus R, Spiess B, et al. A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood loss and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting. Circulation 1995;92(8):2236-44. [MEDLINE: 7554207]
Licker 1999 {published data only}
Lim 2002 {published data only}
Loef 2002 {published data only}
  • Loef BG, Epema AH, Navis G, Ebels T, van Oeveren W, Henning RH. Off-pump coronary revascularization attenuates transient renal damage compared with on-pump coronary revascularization. Chest 2002;121(4):1190-4. [MEDLINE: 11948052]
MacGregor 1994 {published data only}
  • MacGregor DA, Butterworth JF 4th, Zaloga CP, Prielipp RC, James R, Royster RL. Hemodynamic and renal effects of dopexamine and dobutamine in patients with reduced cardiac output following coronary artery bypass grafting. Chest 1994;106:835-41. [MEDLINE: 7915979]
Mahesh 2008 {published data only}
  • Mahesh B, Yim B, Robson D, Pillai R, Ratnatunga C, Pigott D. Does furosemide prevent renal dysfunction in high-risk cardiac surgical patients? Results of a double-blinded prospective randomised trial. European Journal of Cardiothoracic Surgery 2008;33:370-6. [PUBMED: PMID: 18243724]
Mahmood 2007 {published data only}
Memmo 2011 {published data only}
  • Memmo A, Carozzo A, Landoni G, Fano G, Sottocorna O, Bignami E, et al. Perioperative fenoldopam for the prevention of acute renal failure in non-cardiac surgery, randomized clinical trial. Signa Vitae 2011;6(1):14-9.
Neimark 2005 {published data only}
  • Neimark MI, Merkulov IV, Flat MK. Renal protective function in surgical treatment for chronic infrarenal aortic aneurysms. Anesteziologiia i Reanimatologiia 2005;4:18-22. [MEDLINE: 16206579]
Nguyen 2001 {published data only}
Nguyen 2002 {published data only}
  • Nguyen NT, Perez RV, Fleming N, Rivers R, Wolfe BM. Effect of prolonged pneumoperitoneum on intraoperative urine output during laparoscopic gastric bypass. Journal of American College of Surgeons 2002;195:476-83. [MEDLINE: 12375752]
Niiya 2001 {published data only}
  • Niiya S, Fukusaki M, Nakamura T, Miyoshi H, Ogata K, Miyako M. Effects of dopamine and dobutamine on renal function and urinary excretion of prostaglandin E2 in elderly postoperative patients [In Japanese]. Japanese Journal of Anesthesiology 2001;50:122-6. [MEDLINE: 11244764]
Nuutinen 1976 {published data only}
O'Hara 2002A {published data only}
  • O'Hara JF, Sprung J. The effect of dopamine on renal function in solitary partial nephrectomy patients. Anesthesia and Analgesia 2002;94(Suppl):104.
Oliver 2006 {published data only}
  • Oliver WC, Nuttall GA, Cherry KJ, Decker PA, Bower T, Ereth MH. A comparison of fenoldopam with dopamine and sodium nitroprusside in patients undergoing cross-clamping of the abdominal aorta. Anesthesia and Analgesia 2006;103(4):833-40. [MEDLINE: 17000789]
Ovrum 2004 {published data only}
  • Ovrum E, Tangen G, Tollofsrud S, Oystese R, Ringdal MAL, Istad R. Cold blood cardioplegia versus cold crystalloid cardioplegia: a prospective randomized study of 1440 patients undergoing coronary artery bypass grafting. The Journal of Thoracic and Cardiovascular Surgery 2004;128(6):860-5. [MEDLINE: 15573070]
Pain 1991 {published data only}
Paul 1986 {published data only}
Pavoni 1998 {published data only}
  • Pavoni V, Verri M, Ferraro L, Volta CA, Paparella L, Capuzzo M, et al. Plasma dopamine concentration and effects of low dopamine doses on urinary output after major vascular surgery. Kidney International 1998;53(Suppl 66):S75-80. [MEDLINE: 9573579]
Petry 1992 {published data only (unpublished sought but not used)}
  • Petry A, Wulf H, Blomer U, Wawersik J. Nifedipine versus nitroglycerin in aortocoronary bypass surgery [Nifedipin versus nitrat bei aorto-koronaren bypassoperationen [German]]. Anaesthesist 1992;41:39-46. [: 1536439]
Piper 2003 {published data only}
Plusa 1991 {published data only}
  • Plusa SM, Clark NW. Prevention of postoperative renal dysfunction in patients with obstructive jaundice: a comparison of mannitol-induced diuresis and oral sodium taurocholate. Journal of the Royal College of Surgeons of Edinburgh 1991;36:303-5. [MEDLINE: 1757907]
Priano 1993 {published data only}
Prifti 2001 {published data only}
  • Prifti E, Boinacchi M, Frati G, Giunti G, Proietti P, Leacche M, et al. Beating heart myocardial revascularization on extracorporeal circulation in patients with end-stage coronary artery disease. Cardiovascular Surgery 2001;9(6):608-13. [MEDLINE: 11604346]
Regragui 1995 {published data only}
Riess 2000 {published data only}
  • Riess FC, Moshar S, Bader R, Schofer J, Lower C, Kremer P, et al. Clinical outcome of patients with and without renal impairment undergoing a minimally invasive LIMA-to-LAD bypass operation. Heart Surgery Forum 2000;3(4):313-8. [MEDLINE: 11178293]
Ryckwaert 1995 {published data only}
  • Ryckwaert F, Calvert B, Peckstaing M, Wintrebert P, Ribstein J, Colson P. Effects of enalaprilate on haemodynamics and renal function during cardiac surgery in patients with preoperative heart failure. British Journal of Anaesthesia 1995;74:A103.
Sanders 2001 {published data only}
Sezai 2006 {published data only}
  • Sezai A, Shiono M, Hata M, Iida M, Wakui S, Soeda M, et al. Efficacy of continuous low-dose human atrial natriuretic peptide given from the beginning of cardiopulmonary bypass for thoracic aortic surgery. Surgery Today 2006;36:508-14. [MEDLINE: 16715419]
Sherry 1997 {published data only}
  • Sherry E, Tooley MA, Bolsin SN, Monk CR, Wilcox J. Effect of dopexamine hydrochloride on renal vascular resistance index and haemodynamic responses following coronary artery bypass graft surgery. European Journal of Anaesthesiology 1997;14:184-9. [MEDLINE: 9088818]
Skillman 1975 {published data only}
Stanitsh 2002 {published data only}
  • Stanitsh MB, Sindjelitsh RB, Neshkovitsh V, Davidovitsh LB, Lotina SL. Renal protection during the operation of infra-renal aorta [In Serbian]. Srpski Archv Za Celokupno Lekarstvo (Serbian) 2002;130(5-6):168-72.
Straka 2004 {published data only}
  • Straka Z, Widimsky P, Jirasek K, Stros P, Votava J, Vanek T, et al. Off-pump versus on-pump coronary surgery: final results from a prospective randomized study PRAGUE-4. Annals of Thoracic Surgery 2004;77:789-93. [MEDLINE: 14992872]
Tataranni 1994 {published data only}
Torsello 1993 {published data only}
  • Torsello G, Kutkuhn B, Kniemeyer H, Sandmann W. Prevention of acute renal failure after suprarenal aortic surgery: results of a pilot study. Zentralblatt fur Chirurgie 1993;118:390-4. [MEDLINE: 8372519]
Tripathy 1996 {published data only}
  • Tripathy U, Dhiman RK, Attari A, Katariya RN, Ganguly NK, Chawla YK, et al. Preoperative bile salt administration versus bile salt refeeding in obstructive jaundice. The National Medical Journal of India 1996;9(2):66-9. [MEDLINE: 8857040]
Ueki 1995 {published data only}
  • Ueki M, Yokono S, Nogaya J, Taei S, Komatsu H, Ogli K. Effect of ulinastatin on renal function after subrenal aortic cross-clamping. The Japanese Journal of Anesthesiology 1995;44(3):357-61. [MEDLINE: 7609298]
Vogt 1996 {published data only}
  • Vogt NH, Bothner U, Lerch G, Lindner KH, Georgieff M. Large-dose administration of 6% hydroxyethyl starch 200/0.5 for total hip arthroplasty: plasma homeostasis, hemostasis, and renal function compared to use of 5% human albumin. Anesthesia and Analgesia 1996;83:262-8. [MEDLINE: 8694303]
Vogt 1999 {published data only}
Weisz 2009 {published data only}
  • Weisz G, Filby SJ, Cohen MG, Allie DE, Weinstock BS, Kyriazis D, et al. Safety and performance of targeted renal therapy: the Be-RITe! Registry. Journal of Endovascular Therapy 2009;16(1):1-12. [PUBMED: PMID: 19281283]
Welch 1993 {published data only}
Wool 2010 {published data only}
  • Wool DB, Lemmens HJM, Brodsky JB, Solomon H, Chong KP, Morton JM. Intraoperative fluid replacement and postoperative creatine phosphokinase levels in laparoscopic bariatric patients. Obesity Surgery 2010;20:698-701. [PUBMED: PMID: 20198451]

Additional references

  1. Top of page
  2. AbstractRésumé scientifique
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. References to studies awaiting assessment
  24. Additional references
  25. References to other published versions of this review
Anderson 1986
  • Anderson SG, Rennke HG, Brenner BM. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in rat. The Journal of Clinical Investigation 1986;77:1993-2000. [PUBMED: PMID: 3011863]
ANZICS CTG 2000
Bellomo 2007
  • Bellomo R, Kellum JA, Ronco C. Defining and classifying acute renal failure: from advocacy to consensus and validation of the RIFLE criteria. Intensive Care Medicine 2007;33:409-13. [PUBMED: PMID: 17165018 ]
Brazel 1996
Brienza 2009
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Brown 1998
Chatterjee 2005
Deeks 2008
  • Deeks JJ, Higgins JPT, Altman DG (editors), on behalf of the Cochrane Statistical Methods Group. Chapter 9:  Analysing data and undertaking meta-analyses: In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.0 [updated February 2008]. The Cochrane Collaboration, 2008. www.cochrane-handbook.org.
Dillingham 1986
Edelstein 1997
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Endre 2011
  • Endre ZH, Pickering JW, Walker RJ, Davarajan P, Edelstein CL, Bonventre JV, et al. Improved performance of urinary biomakers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function. Kidney International 2011;79:1119-30. [PUBMED: 21307838]
Harris 1987
Higgins 2008
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.0.0 [updated February 2008]. The Cochrane Collaboration, 2008. www.cochrane-handbook.org.
Johnson 2006
Kay 2003
  •  Kay J, Chow WH, Chan TM, Lo SK, Kwok OH, Yop A, et al. Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial. JAMA 2003;289:553-8. [PUBMED: PMID: 12578487]
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Maiese 2005
Marin-Grez 1986
McDonald 1964
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Mehta 2007
  • Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute Kidney Injury Network. Report of an initiative to improve outcomes in acute kidney injury. Critical Care 2007;11:R31. [PUBMED: PMID: 17331245 ]
Moitra 2009
  • Moitra V, Gaffney A, Playford H, Sladen RN. What is the best means of preventing perioperative renal injury?. Fleisher LA (editor). Evidence–Based Practice of Anesthesiology. 2nd Edition. Philadelphia: Saunders Elsevier, 2009. [: ISBN: 978-1-4160-5996-7]
Moore 2011
Morcos 2004
Renton 2005
Schrier 1984
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Schrier 1991
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Seri 1988
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  • Sonnenberg H, Honrath U, Chong CK, Wilson DR. Atrial natriuretic factor inhibits sodium transport in medullary collecting duct. American Journal of Physiology-Renal Physiology 1986;250:F963-6. [PUBMED: PMID: 2940876]
Tepel 2000
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References to other published versions of this review

  1. Top of page
  2. AbstractRésumé scientifique
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Notes
  20. Characteristics of studies
  21. References to studies included in this review
  22. References to studies excluded from this review
  23. References to studies awaiting assessment
  24. Additional references
  25. References to other published versions of this review
Zacharias 2005
Zacharias 2008