Fenoldopam for preventing and treating acute kidney injury (Protocol)

Cochrane Database of Systematic Reviews

Fenoldopam for preventing and treating acute kidney injury (Protocol) Esezobor CI, Bhatt GC, Effa EE, Hodson EM

Esezobor CI, Bhatt GC, Effa EE, Hodson EM. Fenoldopam for preventing and treating acute kidney injury. Cochrane Database of Systematic Reviews 2017, Issue 12. Art. No.: CD012905. DOI: 10.1002/14651858.CD012905.

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Fenoldopam for preventing and treating acute kidney injury (Protocol) Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS HEADER . . . . . . . . . . ABSTRACT . . . . . . . . . BACKGROUND . . . . . . . OBJECTIVES . . . . . . . . METHODS . . . . . . . . . ACKNOWLEDGEMENTS . . . REFERENCES . . . . . . . . ADDITIONAL TABLES . . . . . APPENDICES . . . . . . . . CONTRIBUTIONS OF AUTHORS DECLARATIONS OF INTEREST . SOURCES OF SUPPORT . . . .

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[Intervention Protocol]

Fenoldopam for preventing and treating acute kidney injury Christopher I Esezobor1 , Girish C Bhatt2 , Emmanuel E Effa3 , Elisabeth M Hodson4 1 Department

of Paediatrics, College of Medicine, University of Lagos, Lagos, Nigeria. 2 Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Bhopal, India. 3 Internal Medicine, College of Medical Sciences, University of Calabar, Calabar, Nigeria. 4 Cochrane Kidney and Transplant, Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, Australia Contact address: Christopher I Esezobor, Department of Paediatrics, College of Medicine, University of Lagos, Lagos University Teaching Hospital, Lagos, Lagos, 101014, Nigeria. [email protected]. Editorial group: Cochrane Kidney and Transplant Group. Publication status and date: New, published in Issue 12, 2017. Citation: Esezobor CI, Bhatt GC, Effa EE, Hodson EM. Fenoldopam for preventing and treating acute kidney injury. Cochrane Database of Systematic Reviews 2017, Issue 12. Art. No.: CD012905. DOI: 10.1002/14651858.CD012905. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: This review aims to assess the benefits and harms of fenoldopam for the prevention or treatment of AKI in children and adults.

BACKGROUND

Description of the condition Acute kidney injury (AKI) is characterised by the abrupt loss of the kidney’s excretory function with accumulation of waste products (urea, creatinine) with or without changes in urine output (Bellomo 2012). The causes of AKI have been divided into: prerenal (caused by decreased renal perfusion, e.g. volume depletion due to vomiting and diarrhoea or decreased arterial pressure due to heart failure or sepsis), intrinsic (tubular, glomerular, interstitial or vascular), and post-renal (caused by inadequate drainage of urine, e.g. prostate hypertrophy, neurogenic bladder, bladder or prostate cancer) (Greenberg 2009). In one large prospective study of patients with severe AKI, the common attributable causes were septic shock (47%), post major surgery (34%), cardiogenic shock (27%) and hypovolaemia (26%) (Uchino 2005). AKI is a common syndrome that is independently associated with increased risk of mortality, morbidity and cost of hospitalisation (Mehta 2016). A meta-analysis using the Kidney Disease: Improv-

ing Global Outcomes (KDIGO) definition (KDIGO 2012) found that 1/5 adults and 1/3 children worldwide experience AKI during hospital care (Susantitaphong 2013). The meta-analysis further showed a pooled mortality rate of 23.9% and 13.8% in adults and children, respectively (Susantitaphong 2013). In Africa, AKIrelated mortality rate exceeds 30% for both adults and children, but rose to more than 70% to 80% when dialysis was needed but not provided (Olowu 2016). Also, patients with AKI have a nine times pooled risk of developing chronic kidney disease and two times higher risk of premature death compared to controls (Coca 2012). Furthermore, a study exploring the economic impact of AKI in England determined that the annual cost of AKI-related inpatient care in England was approximately £1.02 billion, just over 1% of the National Health Service budget (Kerr 2014). In addition, the lifetime cost of post-discharge care for people who had AKI during hospital admission in 2010-11 was estimated to be £179 million (Kerr 2014). In recent years, several consensus groups proposed criteria for the definition and staging of AKI, using increase in serum creatinine (SCr) (or decrease in glomerular filtration rate (GFR)) and reduc-


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tion in urine output. These consensus definitions for AKI include the RIFLE (Risk, Injury, Failure, Loss and End stage) criteria proposed by the Acute Dialysis Quality Initiative, the Acute Kidney Injury Network (AKIN) criteria and, more recently, the Kidney Disease: Improving Global Outcome guideline (Table 1) (Bellomo 2004; KDIGO 2012; Mehta 2007). Utilisation of changes in SCr level in these consensus definitions stems from accumulated evidence that small increases in SCr are associated with increased duration and costs of hospitalisation and poor outcomes (Lassnigg 2004; Levy 2005). In most cases of AKI, there is a significant disruption in renal haemodynamics even in the presence of effective systemic volume (Tiwari 2005; Wang 2012). Through the interaction of several systems such as the sympathetic nervous system and renin-angiotensin system, blood supply to the essential organs such as the heart, brain and the adrenal is preserved at the expense of the kidneys, gut and skin. At the renal microcirculatory level, imbalance between vasodilators and vasoconstrictors leads to variable blood flow from one region of the nephron to another. Even in sepsisinduced AKI, the most common form of AKI, microcirculatory disturbance is a key pathogenetic mechanism (De Backer 2002; Tiwari 2005; Wang 2012). The clinical phenotype of these renal haemodynamic changes is a reduction in GFR, fluid overload and electrolyte derangement. The management of AKI is mainly supportive with maintenance of optimal fluid and haemodynamic status, treatment of the underlying illness, nutritional support, avoidance of nephrotoxic drugs, and provision of renal replacement therapy (RRT) (KDIGO 2012). In most parts of the developing world where RRT is not readily available, preventable death from AKI is high (Olowu 2016). Fluid administration in the setting of hypovolaemia, avoidance or readjustment of nephrotoxic drugs are the proven interventions for prevention of AKI while loop diuretics, mannitol, vasodilator therapy (dopamine, fenoldopam, natriuretic peptides), statins, and adenosine antagonists) have been used with varying success (Bagshaw 2007; Bhat 2006; Gillies 2015; Molnar 2011; Nigwekar 2009; Yang 2014).

Description of the intervention Fenoldopam is a short-acting benzazepine selective dopaminergic A1 (DA1) receptor agonist with slightly more potent activity at the D1 receptor than dopamine (Hahn 1982). Unlike dopamine, it has no β-adrenergic or α-adrenergic receptor activity (Singer 1998). In the kidneys, the D1 receptors are located in the renal arteries, and afferent and efferent arterioles, where activation leads to vasodilation and improved renal blood flow (Pollock 1990). In addition, activation of DI receptors on the renal tubules causes natriuresis and diuresis (Girbes 1990). It is administered intravenously as a continuous infusion because of its poor oral bioavailability and short half-life (Weber 1988; Ziemniak 1985). Similar to dopamine it induces natriuresis

(Girbes 1990), but unlike dopamine it reduces systemic vascular resistance while promoting renal blood flow (Goldberg 1984). Because it selectively acts on DA1 receptors, it is thought to promote more blood flow in the renal medulla than in the cortex (Aravindan 2006). Through these effects, fenoldopam may prevent AKI, ameliorate its course and in established AKI enhance prompt resolution. Nonetheless, fenoldopam has been associated with adverse effects, notably hypotension and the need for vasopressors, which require balancing its benefits with the risk of harm (Gillies 2015).

How the intervention might work In theory, by improving renal blood flow and decreasing energy requirement of the tubules via inhibition of sodium reabsorption, fenoldopam may help prevent AKI in patients with ischaemic, septic or nephrotoxic insults. Furthermore, in established AKI, fenoldopam may hasten resolution of AKI and prevent further kidney damage by improving renal microcirculation especially to the outer medulla, relieving intraluminal tubular obstruction and reducing energy demand of the tubules via inhibition of Na+ /K + -ATPase. Overall, by improving urine output, fenoldopam may help to prevent fluid overload which is a major risk factor for adverse outcomes and increased utilization of hospital resources in AKI.

Why it is important to do this review Four reviews, all non-Cochrane, showed that fenoldopam reduces the risk of AKI (Gillies 2015; Landoni 2007; Landoni 2008; Zangrillo 2012), whereas a Cochrane review, in which data on dopamine and its analogues including fenoldopam were combined, showed no added advantage in patients undergoing surgery (Zacharias 2013). In two of the reviews fenoldopam showed no benefit in terms of mortality and the use of RRT (Gillies 2015; Zangrillo 2012). A major limitation of the reviews is the focus on mostly adults undergoing major surgeries or cardiac surgeries, which constrains their generalisability. Furthermore, in two of the reviews, data for prevention and treatment of AKI were analysed together (Landoni 2007; Zangrillo 2012). In addition, more recently, a better powered randomised control trial (RCT) investigating the role of fenoldopam for the treatment of AKI after cardiac surgery was prematurely stopped after interim analysis because of futility (Bove 2014). Data from this and another recently published study (Biancofiore 2015) may change the conclusion reached in previous reviews or the weight of the summary effect. Hence a need to perform a new review that addresses the shortcomings of the previous reviews and include data from more recent studies.


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OBJECTIVES

Secondary outcomes

This review aims to assess the benefits and harms of fenoldopam for the prevention or treatment of AKI in children and adults.

1. Change in SCr or measures of GFR from baseline 2. Urine output (change in urine output from baseline) 3. Duration of mechanical ventilation 4. Duration of ICU stay 5. Adverse events (changes in blood pressure, number needing vasopressors and number with headaches, arrhythmias and raised intraocular pressure)

METHODS

Criteria for considering studies for this review Search methods for identification of studies Types of studies All RCTs and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at fenoldopam for the prevention or treatment of AKI.

Types of participants

Inclusion criteria

Children and adults at risk of AKI or with AKI will be included. Critically ill persons and those undergoing major surgeries or interventions are considered at risk of AKI (KDIGO 2012). AKI will be defined according to the definitions used by the authors of individual studies.

Exclusion criteria

Adults and children with AKI due to glomerular disease, obstructive uropathy, haemolytic uraemic syndrome, delayed graft function and post-transplant AKI will be excluded.

Types of interventions We will include studies comparing fenoldopam versus placebo, no intervention or standard care for the prevention or treatment of AKI.

Types of outcome measures

Electronic searches We will search the Cochrane Kidney and Transplant Specialised Register through contact with the Information Specialist using search terms relevant to this review. The Specialised Register contains studies identified from the following several sources. 1. Monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL) 2. Weekly searches of MEDLINE OVID SP 3. Handsearching of kidney-related journals and the proceedings of major kidney conferences 4. Searching of the current year of EMBASE OVID SP 5. Weekly current awareness alerts for selected kidney and transplant journals 6. Searches of the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Studies contained in the Specialised Register are identified through search strategies for CENTRAL, MEDLINE, and EMBASE based on the scope of Cochrane Kidney and Transplant. Details of these strategies, as well as a list of handsearched journals, conference proceedings and current awareness alerts, are available in the Specialised Register section of information about Cochrane Kidney and Transplant. See Appendix 1 for search terms to be used in strategies for this review.

Searching other resources 1. Reference lists of review articles, relevant studies and clinical practice guidelines. 2. Letters seeking information about unpublished or incomplete studies to investigators known to be involved in previous studies.

Primary outcomes

1. Development of AKI 2. Need for RRT within 30 days after intervention 3. Duration of RRT 4. All-cause mortality: this will include mortality at or before 30 days and late mortality (after 30 days)

Data collection and analysis

Selection of studies


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The search strategy described will be used to obtain titles and abstracts of studies that may be relevant to the review. The titles and abstracts will be screened independently by two authors, who will discard studies that are not applicable; however studies and reviews that might include relevant data or information on studies will be retained initially. Two authors will independently assess retrieved abstracts and, if necessary the full text, of these studies to determine which studies satisfy the inclusion criteria.

Data extraction and management Data extraction will be carried out independently by two authors using standard data extraction forms. Studies reported in nonEnglish language journals will be translated before assessment. Where more than one publication of one study exists, reports will be grouped together and the publication with the most complete data will be used in the analyses. Where relevant outcomes are only published in earlier versions these data will be used. Any discrepancy between published versions will be highlighted.

Assessment of risk of bias in included studies The following items will be independently assessed by two authors using the risk of bias assessment tool (Higgins 2011) (see Appendix 2). • Was there adequate sequence generation (selection bias)? • Was allocation adequately concealed (selection bias)? • Was knowledge of the allocated interventions adequately prevented during the study? ◦ Participants and personnel (performance bias) ◦ Outcome assessors (detection bias) • Were incomplete outcome data adequately addressed (attrition bias)? • Are reports of the study free of suggestion of selective outcome reporting (reporting bias)? • Was the study apparently free of other problems that could put it at a risk of bias?

Measures of treatment effect Measures of treatment effect for prevention studies will be analysed separately from treatment studies. For dichotomous outcomes (number developing AKI, needing RRT, all-cause mortality and adverse effects) results will be expressed as risk ratios (RR) with 95% confidence intervals (CI). Where continuous scales of measurement are used to assess the effects of treatment (change in SCr or measures of GFR from baseline, change in urine output from baseline, duration of RRT, mechanical ventilation and ICU stay), the mean difference (MD) will be used, or the standardised mean difference (SMD), if different scales have been used. If standard deviations (SD) are not available from the authors of the studies we will impute SD using Cochrane methods.

Unit of analysis issues We will use data from the first phase of cross-over studies if these data are available. Data that are expressed in different scales will be analysed using standardized mean difference.

Dealing with missing data We will report missing data including dropouts in various studies. We will try to find out the reasons for dropouts. In case of missing or incomplete data or where the reasons for dropouts are not reported, we will contact the study authors for the information. Quantitative analysis will be performed on an Intention to treat (ITT) basis.

Assessment of heterogeneity We will first assess the heterogeneity by visual inspection of the forest plot. We will quantify statistical heterogeneity using the I² statistic, which describes the percentage of total variation across studies that is due to heterogeneity rather than sampling error (Higgins 2003). A guide to the interpretation of I² values will be as follows: • 0% to 40%: might not be important; • 30% to 60%: may represent moderate heterogeneity; • 50% to 90%: may represent substantial heterogeneity; • 75% to 100%: considerable heterogeneity. The importance of the observed value of I² depends on the magnitude and direction of treatment effects and the strength of evidence for heterogeneity (e.g. P-value from the Chi² test, or a confidence interval for I²) (Higgins 2011).

Assessment of reporting biases A detailed electronic search and search of trial registries will be done to minimize publication bias. If 10 or more studies are identified, a funnel plot will be used to assess for the potential existence of small study bias (Higgins 2011). A triangular 95% CI based on a fixed effect meta-analysis will be used to identify asymmetry.

Data synthesis Data for prevention of AKI will be pooled separately from that for treatment of AKI using the random-effects model, but the fixed-effect model will also be used to ensure robustness of the model chosen and susceptibility to outliers. For cross-over studies we will use data from first phase of study, if available. The data will be expressed as mean difference (MD) with 95% CI in case of continuous data and risk ratio (RR) with 95% CI in case of categorical data.


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Subgroup analysis and investigation of heterogeneity We plan to carry out the following prespecified subgroup analysis for the primary outcomes. 1. Different exposures: cardiac surgery, major non-cardiac surgery, sepsis, radiocontrast agents 2. Different risks: diabetics versus non-diabetics 3. Prevention and treatment of AKI

Sensitivity analysis We will perform sensitivity analyses in order to investigate the robustness of the estimate and explore the influence of the following factors on effect size: repeating the analysis excluding unpublished studies and excluding the studies at high risk of bias.

’Summary of findings’ tables We will present the main results of the review in ’Summary of findings’ tables. These tables present key information concerning the quality of the evidence, the magnitude of the effects of the interventions examined, and the sum of the available data for the main outcomes (Schunemann 2011a). The ’Summary of findings’ tables also include an overall grading of the evidence related to

each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach (GRADE 2008; GRADE 2011). The GRADE approach defines the quality of a body of evidence as the extent to which one can be confident that an estimate of effect or association is close to the true quantity of specific interest. The quality of a body of evidence involves consideration of within-trial risk of bias (methodological quality), directness of evidence, heterogeneity, precision of effect estimates and risk of publication bias (Schunemann 2011b). We plan to present the following outcomes in the ’Summary of findings’ tables. 1. Development of AKI 2. Need for RRT within 30 days after intervention 3. Duration of RRT 4. All-cause 30-day mortality and mortality after 30 days 5. Urine output 6. Adverse events

ACKNOWLEDGEMENTS We wish to thank the referees for their comments and feedback during the preparation of this protocol.

REFERENCES

Additional references Aravindan 2006 Aravindan N, Samuels J, Riedel B, Shaw A. Fenoldopam improves corticomedullary oxygen delivery and attenuates angiogenesis gene expression in acute ischemic renal injury. Kidney & Blood Pressure Research 2006;29(3):165–74. MEDLINE: 16931895 Bagshaw 2007 Bagshaw SM, Delaney A, Haase M, Ghali WA, Bellomo R. Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis. Critical Care & Resuscitation 2007;9(1):60–8. MEDLINE: 17352669 Bellomo 2004 Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute Dialysis Quality Initiative workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Critical Care (London, England) 2004;8(4):R204–12. MEDLINE: 15312219 Bellomo 2012 Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet 2012;380(9843):756–66. MEDLINE: 22617274

Bhat 2006 Bhat MA, Shah ZA, Makhdoomi MS, Mufti MH. Theophylline for renal function in term neonates with perinatal asphyxia: a randomized, placebo-controlled trial. Journal of Pediatrics 2006;149(2):180–4. MEDLINE: 16887430 Biancofiore 2015 Biancofiore G, Bindi ML, Miccoli M, Cerutti E, Lavezzo B, Pucci L, et al. Intravenous fenoldopam for early acute kidney injury after liver transplantation. Journal of Anesthesia 2015;29(3):426–32. MEDLINE: 25433498 Bove 2014 Bove T, Zangrillo A, Guarracino F, Alvaro G, Persi B, Maglioni E, et al. Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial. JAMA 2014;312(21):2244–53. MEDLINE: 25265449 Coca 2012 Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney International 2012;81(5):442–48. MEDLINE: 22113526 De Backer 2002 De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis.


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American Journal Respiratory & Critical Care Medicine 2002; 166(1):98–104. MEDLINE: 12091178 Gillies 2015 Gillies MA, Kakar V, Parker RJ, Honore PM, Ostermann M. Fenoldopam to prevent acute kidney injury after major surgery- a systematic review and meta-analysis. Critical Care (London, England) 2015;19:449. MEDLINE: 26703329 Girbes 1990 Girbes AR, Smit AJ, Meijer S, Reitsma WD. Renal and endocrine effects of fenoldopam and metoclopramide in normal man. Nephron 1990;56(2):179–15. MEDLINE: 1978736 Goldberg 1984 Goldberg LI. Dopamine receptors and hypertension. Physiologic and pharmacologic implications. American Journal of Medicine 1984;77(4A):37–44. MEDLINE: 6148892 GRADE 2008 Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924–6. MEDLINE: 18436948 GRADE 2011 Guyatt G, Oxman A D, Akl E A, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64:383–94. MEDLINE: 22818160 Greenberg 2009 Greenberg A. Primer on Kidney Diseases. 5th Edition. Philadelphia: Saunders, 2009. [eBook ISBN: 9781437721102] Hahn 1982 Hahn RA, Wardell JR Jr, Sarau HM, Ridley PT. Characterization of the peripheral and central effects of SK&F 82526, a novel dopamine receptor agonist. Journal of Pharmacology & Experimental Therapeutics 1982;223(2): 305–13. MEDLINE: 6127401 Higgins 2003 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327 (7414):557–60. MEDLINE: 12958120

Nephrology Dialysis Transplantation 2014;29(7):1362–8. MEDLINE: 24753459 Landoni 2007 Landoni G, Biondi-Zoccai GG, Tumlin JA, Bove T, De Luca M, Calabrò MG, et al. Beneficial impact of fenoldopam in critically ill patients with or at risk for acute renal failure: a meta-analysis of randomized clinical trials. American Journal of Kidney Diseases 2007;49(1):56–68. MEDLINE: 17185146 Landoni 2008 Landoni G, Biondi-Zoccai GG, Marino G, Bove T, Fochi O, Maj G, et al. Fenoldopam reduces the need for renal replacement therapy and in-hospital death in cardiovascular surgery: a meta-analysis. Journal of Cardiothoracic & Vascular Anesthesia 2008;22(1):27–33. MEDLINE: 18249327 Lassnigg 2004 Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann LM, Druml W, Bauer P, et al. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. Journal of the American Society of Nephrology 2004;15(6):1597–605. MEDLINE: 15153571 Levy 2005 Levy MM, Macias WL, Vincent JL, Russell JA, Silva E, Trzaskoma B, et al. Early changes in organ function predict eventual survival in severe sepsis. Critical Care Medicine 2005;33(10):2194–201. MEDLINE: 16215369 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 (London, England) 2007;11(2):R31. MEDLINE: 17331245 Mehta 2016 Mehta RL, Burdmann EA, Cerda J, Feehally J, Finkelstein F, Garcia-Garcia G, et al. Recognition and management of acute kidney injury in the International Society of Nephrology 0by25 Global Snapshot: a multinational crosssectional study.[Erratum appears in Lancet. 2016 May 14; 387(10032):1998; PMID: 27203775]. Lancet 2016;387 (10032):2017–25. MEDLINE: 27086173

KDIGO 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney International Supplement 2012;2(1):1–138. [DOI: 10.1038/kisup.2012.1

Molnar 2011 Molnar AO, Coca SG, Devereaux PJ, Jain AK, Kitchlu A, Luo J, et al. Statin use associates with a lower incidence of acute kidney injury after major elective surgery. Journal of the American Society of Nephrology 2011;22(5):939–46. MEDLINE: 21493769 Nigwekar 2009 Nigwekar SU, Navaneethan SD, Parikh CR, Hix JK. Atrial natriuretic peptide for preventing and treating acute kidney injury. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD006028.pub2

Kerr 2014 Kerr M, Bedford M, Matthews B, O’Donoghue D. The economic impact of acute kidney injury in England.

Olowu 2016 Olowu WA, Niang A, Osafo C, Ashuntantang G, Arogundade FA, Porter J, et al. Outcomes of acute kidney

Higgins 2011 Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.


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injury in children and adults in sub-Saharan Africa: a systematic review. The Lancet Global Health 2016;4(4): e242–50. MEDLINE: 27013312 Pollock 1990 Pollock DM, Arendshorst WJ. Tubuloglomerular feedback and blood flow autoregulation during DA1-induced renal vasodilation. American Journal of Physiology 1990;258(3 Pt 2):F627–35. MEDLINE: 1969238 Schunemann 2011a Schünemann HJ, Oxman AD, Higgins JP, Vist GE, Glasziou P, Guyatt GH. Chapter 11: Presenting results and ’Summary of findings’ tables. In: Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Schunemann 2011b Schünemann HJ, Oxman AD, Higgins JP, Deeks JJ, Glasziou P, Guyatt GH. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Singer 1998 Singer I, Epstein M. Potential of dopamine A-1 agonists in the management of acute renal failure. American Journal of Kidney Diseases 1998;31(5):743–55. MEDLINE: 9590183 Susantitaphong 2013 Susantitaphong P, Cruz DN, Cerda J, Abulfaraj M, Alqahtani F, Koulouridis I, et al. World incidence of AKI: a meta-analysis.[Erratum appears in Clin J Am Soc Nephrol. 2014 Jun 6;9(6):1148]. Clinical Journal of the American Society of Nephrology: CJASN 2013;8(9):1482–93. MEDLINE: 23744003 Tiwari 2005 Tiwari MM, Brock RW, Megyesi JK, Kaushal GP, Mayeux PR. Disruption of renal peritubular blood flow in lipopolysaccharide-induced renal failure: role of nitric oxide and caspases. American Journal of Physiology - Renal Physiology 2005;289(6):F1324–32. MEDLINE: 15998845 Uchino 2005 Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Acute renal failure in critically ill patients:

a multinational, multicenter study. JAMA 2005;294(7): 813–8. MEDLINE: 16106006 Wang 2012 Wang Z, Holthoff JH, Seely KA, Pathak E, Spencer HJ 3rd, Gokden N, et al. Development of oxidative stress in the peritubular capillary microenvironment mediates sepsisinduced renal microcirculatory failure and acute kidney injury. American Journal of Pathology 2012;180(2):505–16. MEDLINE: 22119717 Weber 1988 Weber RR, McCoy CE, Ziemniak JA, Frederickson ED, Goldberg LI, Murphy MB. Pharmacokinetic and pharmacodynamic properties of intravenous fenoldopam, a dopamine1-receptor agonist, in hypertensive patients. British Journal of Clinical Pharmacology 1988;25(1):17–21. MEDLINE: 2897206 Yang 2014 Yang B, Xu J, Xu F, Zou Z, Ye C, Mei C, et al. Intravascular administration of mannitol for acute kidney injury prevention: a systematic review and meta-analysis. PLoS ONE (Electronic Resource] 2014;9(1):e85029. MEDLINE: 24454783 Zacharias 2013 Zacharias M, Mugawar M, Herbison GP, Walker RJ, Hovhannisyan K, Sivalingam P, et al. Interventions for protecting renal function in the perioperative period. Cochrane Database of Systematic Reviews 2013, Issue 9. [DOI: 10.1002/14651858.CD003590.pub4 Zangrillo 2012 Zangrillo A, Biondi-Zoccai GG, Frati E, Covello RD, Cabrini L, Guarracino F, et al. Fenoldopam and acute renal failure in cardiac surgery: a meta-analysis of randomized placebo-controlled trials. Journal of Cardiothoracic & Vascular Anesthesia 2012;26(3):407–13. MEDLINE: 22459931 Ziemniak 1985 Ziemniak J, Dubb J, Stote R, Trotman C, Yang W, Allison N, et al. Pharmacokinetic interaction between fenoldopam and acetaminophen: competition for sulfate conjugation [abstract no: 32]. Clinical Pharmacology & Therapeutics 1985;37(240). ∗ Indicates the major publication for the study


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ADDITIONAL TABLES Table 1. Consensus definitions of acute kidney injury

RIFLE classification

AKIN classification

KDIGO classification

Class

GFR/serum Urine out- Stage creatinine put

Serum crea- Urine out- Stage tinine put

Serum crea- Urine outtinine put

Risk

SCr ≥ 1.5 < 0.5 mL/ 1 OR GFR ≥ kg/h for 6 h 25%

SCr ≥ 26.5 < 0.5 mL/ 1 µmol/L OR kg/h for > 6 SCr h ≥ 150% to 200% from baseline

SCr to ≥ ≤ 0.5 mL/ 1.5 to 1.9 kg/h for 6 to times base- 12 h line OR ≥ 26.5 mmol/ L increase

Injury

SCr ≥2 OR < 0.5 mL/ 2 GFR ≥50% kg/h for 12 h

SCr > 200% < 0.5 mL/ 2 to kg/h for > 6 300% from h baseline

SCr to 2.0 0.5 mL/kg/h to 2.9 times for ≥ 12 h baseline

Failure

SCr ≥ 3 OR GFR ≥ 75% OR if baseline SCr ≥ 353.6 µmol/ L SCr > 44. 2 µmol/L

SCr > 300% (> 3 fold) from baseline or if baseline SCr ≥ 353.6 µmol/L SCr ≥ 44.2 µmol/L; also includes patients requiring RRT independent of stage

< 0.3 mL/ 3 kg/h for 24 h OR anuria for 12 h

SCr to 3.0 times baseline OR SCr to ≥ 353.6 mmol/L OR Initiation of RRT OR In patients ≤ 18 years, eGFR to ≤ 35 mL/ min/1.73 m

< 0.3 mL/ 3 kg/h for 24 h OR anuria for 12 h

< 0.3 mL/kg/h for ≥ 24 OR anuria for ≥ 12 h

2

Loss

Complete -loss of kidney function > 4 weeks

--

--

--

--

--

--

ESKD

Complete -loss of kidney function > 3 months

--

--

--

--

--

--

ESKD - end-stage kidney disease; (e)GFR - (estimated) glomerular filtration rate; SCr - serum creatinine


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APPENDICES

Appendix 1. Electronic search strategies

Database

Search terms

CENTRAL

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

MeSH descriptor: [Acute Kidney Injury] explode all trees “acute kidney failure” or “acute renal failure”:ti,ab,kw (Word variations have been searched) “acute kidney injury” or “acute renal injury”:ti,ab,kw (Word variations have been searched) “acute kidney insufficiency” or “acute renal insufficiency”:ti,ab,kw (Word variations have been searched) “acute tubular necrosis”:ti,ab,kw (Word variations have been searched) ARI or AKI or ARF or AKF or ATN:ti,ab,kw (Word variations have been searched) {or #1-#6} MeSH descriptor: [Fenoldopam] this term only fenoldopam:ti,ab,kw (Word variations have been searched) corlopam:ti,ab,kw (Word variations have been searched) skf82526 or “sk&f82526”:ti,ab,kw (Word variations have been searched) {or #8-#11} {and #7, #12}

MEDLINE

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

exp Acute Kidney Injury/ (acute kidney failure or acute renal failure).tw. (acute kidney injur$ or acute renal injur$).tw. (acute kidney insufficie$ or acute renal insufficie$).tw. acute tubular necrosis.tw. (ARI or AKI or ARF or AKF or ATN).tw. or/1-6 Fenoldopam/ fenoldopam.tw. corlopam.tw. (skf82526 or “sk&f82526”).tw. or/8-11 and/7,12

EMBASE

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

acute kidney failure/ acute kidney tubule necrosis/ (acute kidney failure or acute renal failure).tw. (acute kidney injur$ or acute renal injur$).tw. (acute kidney insufficie$ or acute renal insufficie$).tw. acute tubular necrosis.tw. (ARI or AKI or ARF or AKF or ATN).tw. or/1-7 exp fenoldopam/ fenoldopam.tw. corlopam.tw. (skf82526 or “sk&f82526”).tw. or/9-12 and/8,13


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Appendix 2. Risk of bias assessment tool

Potential source of bias

Assessment criteria

Random sequence generation Low risk of bias: Random number table; computer random numSelection bias (biased allocation to interventions) due to inade- ber generator; coin tossing; shuffling cards or envelopes; throwing quate generation of a randomised sequence dice; drawing of lots; minimisation (minimisation may be implemented without a random element, and this is considered to be equivalent to being random) High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention Unclear: Insufficient information about the sequence generation process to permit judgement Allocation concealment Low risk of bias: Randomisation method described that would not Selection bias (biased allocation to interventions) due to inade- allow investigator/participant to know or influence intervention quate concealment of allocations prior to assignment group before eligible participant entered in the study (e.g. central allocation, including telephone, web-based, and pharmacy-controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes) High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or nonopaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure Unclear: Randomisation stated but no information on method used is available Blinding of participants and personnel Low risk of bias: No blinding or incomplete blinding, but the rePerformance bias due to knowledge of the allocated interventions view authors judge that the outcome is not likely to be influenced by participants and personnel during the study by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding Unclear: Insufficient information to permit judgement Fenoldopam for preventing and treating acute kidney injury (Protocol) Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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(Continued)

Blinding of outcome assessment Low risk of bias: No blinding of outcome assessment, but the review Detection bias due to knowledge of the allocated interventions by authors judge that the outcome measurement is not likely to be outcome assessors influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding Unclear: Insufficient information to permit judgement Incomplete outcome data Low risk of bias: No missing outcome data; reasons for missing Attrition bias due to amount, nature or handling of incomplete outcome data unlikely to be related to true outcome (for survival outcome data data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation Unclear: Insufficient information to permit judgement Selective reporting Reporting bias due to selective outcome reporting

Low risk of bias: The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon)


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(Continued)

High risk of bias: Not all of the study’s pre-specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. sub-scales) that were not pre-specified; one or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a metaanalysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study Unclear: Insufficient information to permit judgement Other bias Bias due to problems not covered elsewhere in the table

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

CONTRIBUTIONS OF AUTHORS 1. Draft the protocol: CIE, GCB, EE, EH 2. Study selection: CIE, GCB 3. Extract data from studies: CIE, GCB 4. Enter data into RevMan: CIE, GCB 5. Carry out the analysis: CIE,GCB 6. Interpret the analysis: CIE, GCB, EE, EH 7. Draft the final review: CIE, GCB 8. Disagreement resolution: EH 9. Update the review: CIE, GCB


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DECLARATIONS OF INTEREST • CIE: none known • GCB: Dr Girish C Bhatt has received Indian Council of Medical Research (ICMR) international fellowship (IF) as young scientist for the year 2017-18 in division of Pediatric Nephrology at Montreal’s Children Hospital, Canada. • EE: none known • EH: none known

SOURCES OF SUPPORT Internal sources • College of Medicine of the University of Lagos, Nigeria. Provision of necessary infrastructure support during the preparation of this protocol. • All India Institute of Medical Sciences, Bhopal, India. Provision of necessary infrastructure support during the preparation of this protocol.

External sources • No sources of support supplied


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