Author	Title	Year	Did the Trial Address a Clearly Focused Issue?	Method of Randomization Is Described	Adequate Method of Allocation Concealment Is Described	Adequate Follow-Up at the Conclusion of the Study	Were Patients, Health Workers and Study Personnel “Blind” to Treatment?	Were the Groups Similar at the Start of the Trial?	Aside from the Experimental Intervention, Were the Groups Treated Equally?	Can the Results be Applied in Your Context or to a Local Population?	Were All Clinically Important Outcomes Considered?	Comments
Vasodilators
Lassnigg, A et al.	Lack of renoprotective effects of dopamine and furosemide during cardiac surgery	2000	⊕	⊕	⊕	⊕	?	⊕	⊕	?	⊕	Paper refers to study as double-blinded, but no details of blinding reported. Single center
Dehne, MG et al.	Impairment of renal function after cardiopulmonary bypass is not influenced by dopexamine	2001	⊕	⊖	⊖	⊕	⊖	⊕	⊕	⊖	⊖	Small study (four groups n = 12 each) with no power calculation. No analysis of hard outcomes
Sumeray, M et al.	Low dose dopamine infusion reduces renal tubular injury following cardiopulmonary bypass surgery	2001	⊕	⊕	⊖	⊕	⊕	⊕	⊕	⊖	⊖	Small study with no power calculation. Twelve patients were lost to follow up out of 48 originally randomized.
Yavuz, S et al.	Renal dose dopamine in open heart surgery. Does it protect renal tubular function?	2002	⊕	⊖	⊖	⊕	⊖	⊕	⊕	⊖	⊕	Small, unblinded study (two groups n = 11 each) with no power calculation.
Yavuz, S et al.	Effect of combined dopamine and diltiazem on renal function after cardiac surgery	2002	⊕	⊖	⊖	⊕	⊖	⊕	⊕	⊖	⊕	Small, unblinded study (four groups n = 15 each) with no power calculation.
Bergman, AS et al.	Diltiazem infusion for renal protection in cardiac surgical patients with preexisting renal dysfunction	2002	⊕	⊖	⊖	⊕	?	⊕	⊕	⊖	⊖	Small study (two groups n = 12 each) with no power calculation. GFR measured via creatinine level and iohexol clearance. Only the latter reached statistical significance at postoperative week 3. Paper refers to double-blinding, but no details.
Woo, EB et al.	Dopamine therapy for patients at risk of renal dysfunction following cardiac surgery: Science or fiction?	2002	⊕	⊖	⊖	⊕	⊖	⊕	⊕	⊖	⊖	Eight patients excluded after randomization
Caimmi, PP et al.	Fenoldopam for renal protection in patients undergoing cardiopulmonary bypass	2003	⊕	⊖	⊖	⊕	⊖	⊕	⊕	⊖	⊖
Carcoana, OV et al.	Mannitol and dopamine in patients undergoing cardiopulmonary bypass: A randomized clinical trial	2003	⊕	⊕	⊖	⊕	⊕	⊕	⊕	?	⊖	35 withdrawals prior to allocation
Turker, H et al.	Effects of enalaprilat infusion on hemodynamics and renal function in patients undergoing cardiac surgery	2004	⊕	⊖	⊖	⊕	⊖	⊕	⊕	⊖	⊖	Small study (two groups n = 15 each) with no power calculation. Duration of CPB and cross-clamp time significantly longer for intervention group.
Bove, T et al.	Renoprotective action of fenoldopam in high-risk patients undergoing cardiac surgery: A prospective, double-blind, randomized clinical trial	2005	⊕	⊕	⊕	⊕	?	⊕	⊕	?	⊕	Double blinding is mentioned, but no details reported. Single center
Kaya, K 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	2007	⊕	⊕	⊕	⊕	⊕	⊕	⊕	⊕	⊕	Data from two separate centers
Cogliati, AA et al.	Fenoldopam infusion for renal protection in high-risk cardiac surgery patients: A randomized clinical study	2007	⊕	⊕	?	⊕	⊕	⊕	⊕	?	⊖	Single center Allocation concealment attempted via sealed envelopes, but no description of whether ascertainment was possible.
Witczak, BJ et al.	Renal function after cardiopulmonary bypass surgery in patients with impaired renal function. A randomized study of the effect of nifedipine	2008	⊕	⊕	?	⊕	⊖	⊕	⊕	⊖	⊖	Methodology was well reported, but the randomization method is questionable (anesthesiologist randomly selected envelope). The anesthesiologist also knew the allocation. Small, single-center study with no power calculation.
Ranucci, M et al.	Effects of fenoldopam infusion in complex cardiac surgical operations: A prospective, randomized, double-blind, placebo-controlled study	2010	⊕	⊕	⊕	⊕	⊕	⊕	⊖	?	⊕	Some patients were also given systemic vasodilators or vasoconstrictors. Some received furosemide. Possible confounding. CPB equipment varied between patients.
Anti-Inflammatory
Tang, AT et al.	Leukodepletion reduces renal injury in coronary revascularization: A prospective randomized study	2002	⊕	⊖	⊖	⊕	⊖	⊕	⊕	⊖	⊖	Statistically significant difference in renal injury, although this did not translate to any statistical difference in renal function, and no renal impairment was reported in any patient. Statistical power to detect a difference was not calculated.
McBride, WT et al.	Methylprednisolone favourably alters plasma and urinary cytokine homeostasis and subclinical renal injury at cardiac surgery	2004	⊕	⊖	⊖	⊕	⊖	⊕	⊕	⊖	⊖	Patients and laboratory staff were blinded, but the periop physicians knew the allocation.
Loef, BG et al.	Effect of dexamethasone on perioperative renal function impairment during cardiac surgery with cardiopulmonary bypass	2004	⊕	⊖	⊖	⊕	?	⊖	⊕	⊖	⊖	Paper refers to study as double-blinded, but no details of blinding reported. Small study (two groups n = 10 each) Control patients were younger with lower BMI than the intervention group.
Burns, KE et al.	Perioperative N-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing CABG surgery: A randomized controlled trial	2005	⊕	⊕	⊕	⊕	⊕	⊕	⊕	⊕	⊕	Placebo group had greater history of CHF. Data from two separate centers
Ristikankare, A et al.	Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery	2006	⊕	?	⊖	⊕	?	⊕	⊕	?	⊖	Paper refers to study as double-blinded, but few details of blinding reported. Only states “a similar volume of saline” was given to control groups.
Bolcal, C et al.	Leukodepletion improves renal function in patients with renal dysfunction undergoing on-pump coronary bypass surgery: A prospective randomized study	2007	⊕	⊖	⊖	?	⊖	⊕	⊕	⊖	⊖	Unclear how many patients had follow-up data.
Haase, M et al.	Phase II, randomized, controlled trial of high-dose N-acetylcysteine in high-risk cardiac surgery patients	2007	⊕	⊕	⊕	⊕	⊕	⊕	⊕	⊕	⊕	Data from two separate centers
Sisillo, E et al.	N-acetylcysteine for prevention of acute renal failure in patients with chronic renal insufficiency undergoing cardiac surgery: A prospective, randomized, clinical trial	2008	⊕	⊕	⊖	⊕	⊕	⊕	⊕	?	⊕	Single center Some patients underwent OPCAB. No description of why, but the usage of CPB was similar in both groups.
Barr LF and Kolodner, K	N-acetylcysteine and fenoldopam protect the renal function of patients with chronic renal insufficiency undergoing cardiac surgery	2008	⊕	?	⊖	⊕	?	⊕	⊕	⊖	⊕	Paper reports that randomization was “done in the pharmacy department,” but unclear how. Details of blinding unclear Some issues with protocol violations, but only one patient lost to follow-up.
Adabag, AS et al.	Utility of N-acetylcysteine to prevent acute kidney injury after cardiac surgery: A randomized controlled trial	2008	⊕	⊕	⊖	⊕	⊕	⊕	⊕	?	⊕	At the discretion Of the attending surgeon, four patients randomized to NAC and three randomized to placebo underwent OPCAB. Single VA center study of all male population. May not be generalizable to female patients.
Amr, YM et al.	Effects of dexamethasone on pulmonary and renal functions in patients undergoing CABG with cardiopulmonary bypass	2009	⊕	⊖	⊖	?	?	⊕	⊕	⊖	⊖	Small single-center study with a high risk of bias due to lack of details on methodology.
Natriuretics/Diuretics
Mahesh, B et al	Does furosemide prevent renal dysfunction in high-risk cardiac surgical patients? Results of a double-blinded prospective randomised trial	2008	⊕	⊖	⊖	⊕	?	⊕	⊕	⊖	⊕	Paper refers to study as double-blinded, but no details of blinding reported. Eight patients were lost to follow-up.
Yallop, KG et al.	The effect of mannitol on renal function following cardio-pulmonary bypass in patients with normal pre-operative creatinine	2008	⊕	⊕	⊖	⊕	⊕	⊕	⊕	⊖	⊖	Some patients in both groups also received dopamine and/or furosemide, although this was evenly dispersed between the groups. Nine patients lost to follow-up Follow up only 24 hours postop
Smith, MN et al.	The effect of mannitol on renal function after cardiopulmonary bypass in patients with established renal dysfunction	2008	⊕	⊕	⊖	⊕	⊖	⊕	⊕	⊖	⊖	Perfusionist was not blinded, but the rest of the study personnel were.
Ejaz, AA et al.	Prophylactic nesiritide does not prevent dialysis or all-cause mortality in patients undergoing high-risk cardiac surgery	2009	⊕	⊕	?	⊕	?	⊕	⊕	?	⊕	Study was centrally randomized, but details lacking on concealment. Details of blinding are lacking.
Sezai, A et al.	Influence of continuous infusion of low-dose human atrial natriuretic peptide on renal function during cardiac surgery: A randomized controlled study	2009	⊕	?	?	?	?	⊕	⊕	?	⊖	Randomized by “drawing lots.” Unclear. Details lacking on allocation concealment, blinding, and losses to follow-up. Many patients were given dopamine, which might be a significant confounder.
Operative Techniques
Kocakulak, M et al.	Pulsatile flow improves renal function in high-risk cardiac operations	2005	⊕	⊖	⊖	⊕	⊖	?	⊕	⊖	⊖	Small study (two groups n = 10 each group) with no power calculation. Only preoperative demographic factor analyzed was age.
Sajja, LR et al.	Coronary artery bypass grafting with or without cardiopulmonary bypass in patients with preoperative non-dialysis dependent renal insufficiency: A randomized study	2007	⊕	⊕	⊖	⊕	⊖	⊕	⊕	?	⊖
Boodhwani, M et al.	Effects of mild hypothermia and rewarming on renal function after coronary artery bypass grafting	2009	⊕	⊕	⊕	⊕	⊖	⊕	⊕	?	⊕	Single-center pilot study designed to study neurologic outcomes of temperature management on CPB. Post hoc analysis for renal outcomes.
Presta, P et al.	Can pulsatile cardiopulmonary bypass prevent perioperative renal dysfunction during myocardial revascularization in elderly patients?	2009	⊕	⊕	⊖	⊕	⊖	⊕	⊕	?	⊖
Remote Ischemic Preconditioning
Venugopal, V et al.	Effect of remote ischemic preconditioning on acute kidney injury in nondiabetic patients undergoing coronary artery bypass graft surgery: A secondary analysis of 2 small randomized trials	2010	⊕	⊕	⊖	⊕	⊕	⊕	⊕	?	⊖	Results could have been confounded by significantly longer clamp times in the control group, although a further analysis of AKI on those who only underwent CABG remained significant.
Choi, YS et al.	Effect of remote ischemic preconditioning on renal dysfunction after complex valvular heart surgery: A randomized controlled trial	2011	⊕	⊕	⊖	⊕	⊕	⊕	⊕	?	⊖	Small single-center study.
Zimmerman, RF et al.	Ischemic preconditioning at a remote site prevents acute kidney injury in patients following cardiac surgery	2011	⊕	⊕	⊕	⊕	⊖	⊕	⊕	?	⊖
Sodium Bicarbonate
Haase, M et al.	Sodium bicarbonate to prevent increases in serum creatinine after cardiac surgery: A pilot double-blind, randomized controlled trial	2009	⊕	⊕	⊕	⊕	⊕	⊕	⊕	?	⊕	Single-center pilot study
Kristeller, JL et al.	Lack of effectiveness of sodium bicarbonate in preventing kidney injury in patients undergoing cardiac surgery: A randomized controlled trial	2013	⊕	⊕	?	?	⊕	⊕	⊕	?	⊖	Single center Central randomization, but no details of allocation concealment. No information on drop-outs or losses to follow-up.
Haase, M et al.	Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: A multicenter double-blinded randomized controlled trial	2013	⊕	⊕	⊕	⊕	⊕	⊖	⊕	⊕	⊕	Despite randomization, more patients in the sodium bicarbonate group had chronic kidney disease. Six losses to follow up (all in placebo group). Four patients underwent OPCAB. Fourteen patients were considered non-adherent to protocol.
McGuinness, SP et al.	Sodium bicarbonate infusion to reduce cardiac surgery-associated acute kidney injury: A phase II multicenter double-blind randomized controlled trial	2013	⊕	⊕	⊕	⊕	⊕	⊕	⊕	⊕	⊕	Some aspects of CPB were not standardized across institutions.
Other
Durmaz, I et al.	Prophylactic dialysis in patients with renal dysfunction undergoing on-pump coronary artery bypass surgery	2003	⊕	⊕	⊖	⊕	⊖	⊕	⊕	⊖	⊖	Method of randomization (based on the last digit of the medical record number) is questionable.
Marathias, KP et al.	Preoperative intravenous hydration confers renoprotection in patients with chronic kidney disease undergoing cardiac surgery	2006	⊕	⊖	⊖	⊕	⊖	⊕	⊕	⊖	⊖
Song, YR et al.	Prevention of acute kidney injury by erythropoietin in patients undergoing coronary artery bypass grafting: A pilot study	2009	⊕	⊕	?	⊕	⊕	⊕	⊕	?	⊖	75% of the EPO group and 80% of the control group underwent OPCAB. Questionable generalizability. Study was centrally randomized and allocation was performed via the Internet, but details lacking on concealment.
Nouri-Majalan, N et al.	Effects of allopurinol and vitamin E on renal function in patients with cardiac coronary artery bypass grafts	2009	⊕	⊖	⊖	?	?	⊕	⊕	⊖	⊖
Prowle, JR et al.	Pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery	2011	⊕	⊕	⊕	⊕	⊕	⊕	⊕	?	⊖	Single-center study with 16 fewer patients than number needed for 80% power to detect 50% increase in creatinine. Eight lost to follow up in intervention group and seven in control.
Oh, SW et al.	Erythropoietin improves long-term outcomes in patients with acute kidney injury after coronary artery bypass grafting	2012	⊕	⊕	⊕	?	⊕	⊕	⊕	?	⊖
Ejaz, AA et al.	Effect of uric acid lowering therapy on the prevention of acute kidney injury in cardiovascular surgery	2013	⊕	⊕	?	⊕	?	⊕	⊕	?	⊖	Small single-center study (two groups n = 13 each) No details of blinding and allocation concealment.
Darcin, OT et al.	Effect of iloprost on renal function in patients undergoing coronary artery bypass grafting: A clinical study	2013	⊕	⊖	⊖	?	⊖	⊕	⊕	?	⊖	Single-center study lacking in methodology details.
Meta-Analysis Appraisal
Landoni, G et al.	Fenoldopam reduces the need for renal replacement therapy and in-hospital death in cardiovascular surgery: A meta-analysis	2008	⊕	⊕	⊕	⊕	⊕	⊕	⊕	⊕		Results had low heterogeneity in the primary outcome of interest (RRT).
Adabag, AS et al.	Efficacy of N-acetylcysteine in preventing renal injury after heart surgery: A systematic review of randomized trials	2009	⊕	?	⊕	⊕	⊕	⊕	⊕	⊕		MEDLINE was only database searched for relevant papers. Moderate to high level of heterogeneity on the effects of NAC on maximum change in creatinine, ICU length of stay, and total hospital length of stay, but not for ARI, use of dialysis, or death.
Seabra, VF et al.	Off-pump coronary artery bypass surgery and acute kidney injury: A meta-analysis of randomized controlled trials	2010	⊕	?	⊕	⊕	⊕	⊕	⊕	⊕		MEDLINE was only database searched for relevant papers.
Patel, NL et al.	Pharmacological therapies for the prevention of acute kidney injury following cardiac surgery: A systematic review	2011	⊕	⊕	⊕	⊕	⊕	⊖	⊕	⊕		Significant heterogeneity for several outcomes.
Li, L et al.	The role of remote ischemic preconditioning on postoperative kidney injury in patients undergoing cardiac and vascular interventions: A meta-analysis	2013	⊕	⊕	⊕	⊕	⊕	⊕	⊖	⊕		COI section reports funding from a foundation grant, but unclear if individual authors had any RWIs worth noting.