KDIGO CLINICAL PRACTICE GUIDELINE FOR ACUTE KIDNEY INJURY Online Supplementary Tables March 2012 Abbreviations and Acronyms for Supplemental Tables ∆ Change ↓ Decrease ↑ Increase AAA Abdominal aortic aneurysm ACRF Acute-on-chronic renal failure AKI Acute kidney injury ANP Atrial natriuretic peptide ARF Acute renal failure CABG Coronary artery bypass graft CAD Coronary artery disease CI Confidence interval CI-AKI Contrast-induced acute kidney injury CKD Chronic kidney disease CM Contrast medium CrCl Creatinine clearance CRRT Continuous renal replacement therapy CT Computerized tomography CTS Cardiothoracic surgery CV Cardiovascular CVVH Continuous venovenous hemofiltration CVVHDF Continuous venovenous hemodiafiltration D/5 5% glucose ERT Evidence Review Team eQB Effective blood flow GFR Glomerular filtration rate HCO3 Bicarbonate HD Hemodialysis HF Hemofiltration HVPD High volume peritoneal dialysis i.a. Intrarterial ICU Intensive care unit IHD Intermittent hemodialysis IQR Intraquartile range ITT Intention-to-treat i.v. Intravenous LMWH Low molecular weight heparin NA Not applicable NAC N-acetylcysteine nd Not documented NS Not significant OR Odds ratio PCI Percutaneous coronary intervention PTCA Percutaneous transluminal coronary angioplasty pts Patients RBC Red blood cell RCT Randomized controlled trial RIFLE Risk, Injury, Failure, Loss, End stage renal disease RR Relative risk RRT Renal replacement therapy RVP Return venous pressure SCr Serum creatinine UF Ultrafiltration Supplementary table 1: Summary table of RCTs examining the effect of starch for the prevention of AKI No. analyzed Intervention/Control Event rate Author Year Baseline kidney Study (No randomized) Concomitant RR* Outcome Age Setting Arm 1 Country function duration medication (95%CI) Quality Arm 1 Arm 2 Arm 1 Arm 2 (Arm 2) P value Sepsis Patients Mortality 27% 1.13 NS 28 d Brunkhorst 10% Fair Ringer’s (24%) (0.84-1.50) (0.48) [17] 2008 65 SCr 126.4 μmol/l ICU 28 d 262 274 Hydroxyethyl Per protocol lactate 41% 1.21 NS 90 d Germany starch Fair (34%) (0.97-1.50) (0.09) RRT Brunkhorst 10% Ringer’s 31% 1.63 RRT [17] 2008 65 SCr 126.4 μmol/l ICU nd 261 272 Hydroxyethyl Per protocol 0.001 Fair lactate (19%) (1.20-2.21) Germany starch AKI Brunkhorst 10% Doubling of Ringer’s 35% 1.52 [17] 2008 65 SCr 126.4 μmol/l ICU nd 261 272 Hydroxyethyl Per protocol 0.002 Fair baseline SCr lactate (23%) (1.16-2.00) Germany starch Supplementary table 2: Evidence profile of RCTs examining insulin vs. conventional glucose therapy for the prevention of AKI Directness of Summary of findings # of studies Methodological Total N Consistency the evidence Other Outcome and quality of studies (treatment) across studies generalizability/ considerations Quality of evidence for Qualitative and quantitative description of Importance study design per outcome applicability outcome effect of outcome 2 RCT 6558 No limitations (High) (3257) No important Critical Mortality No uncertainty None High No benefit 1 SR inconsistencies (Crucial) 8315 No limitations (29 trials) 2 RCT 6558 No limitations (High) (3257) No important RRT No uncertainty None High No benefit Critical 1 SR inconsistencies 3629 No limitations (29 trials) 1 RCT 536 Some limitations Sparse AKI N/A No uncertainty Low Uncertain High (High) (247) (-1)a (-1) Balance of potential benefits and harm Quality of overall evidence No benefit. Possible harm from hypoglycemia. High Annotations: a. Study was not blinded. Supplementary table 3: Summary table of RCTs examining the effect of insulin for the prevention of AKI No. analyzed Intervention/Control Baseline Event rate Author Year Study (No randomized) (target blood glucose) Concomitant RR* Outcome Age kidney Setting Arm 1 Country duration medication (95%CI) Quality function Arm 1 Arm 2 Arm 1 Arm 2 (Arm 2) P value Critically Ill Patients Mortality Mortality by NICE-SUGAR [56] Intensive 28% 1.10a Conventional 0.02 Good 90 d 2008 Australia, 3010 3012 glucose (25%) (1.01-1.20) 60 nd ICU 90 d glucose nd Mortality by New Zealand & (3054) (3050) (81-108 22% 1.07a NS (≤180 mg/dl) Good 28 d Canada mg/dl) (21%) (0.97-1.18) (0.17) RRT NICE-SUGAR [56] Intensive 15% 1.06a NS RRT Conventional Good 2008 Australia, 3010 3012 glucose (15%) (0.94-1.20) (0.34) 60 nd ICU 90 d glucose nd New Zealand & (3054) (3050) (81-108 0.8 NS Days of RRT (≤180 mg/dl) -- Good Canada mg/dl) (0.8) (0.39) Sepsis Patients Mortality Intensive Conventional 40% 1.14 NS 90 d Fair Brunkhorst [17] SCr 126.4 247 289 insulin insulin (35%) (0.92-1.42) (0.31) 65 ICU 28 d Per protocol 2008 Germany μmol/l (247) (290) (80-110 (180-200 25% 0.96 NS 28 d Fair mg/dl) mg/dl) (26%) (0.72-1.29) (0.74) RRT Intensive Conventional Brunkhorst [17] SCr 126.4 244 289 insulin insulin 28% 1.22 NS RRT 65 ICU nd Per protocol Fair 2008 Germany μmol/l (247) (290) (80-110 (180-200 (23%) (0.91-1.63) (0.19) mg/dl) mg/dl) AKI Intensive Conventional Doubling of Brunkhorst [17] SCr 126.4 244 289 insulin insulin 31% 1.15 NS 65 ICU nd Per protocol Fair baseline SCr 2008 Germany μmol/l (247) (290) (80-110 (180-200 (27%) (0.88-1.50) (0.25) mg/dl) mg/dl) Annotations: *Calculated by ERT with raw data from original studies when available. When study reported only event rates, calculations were done using percentages. a. NICE-SUGAR: Mortality by 90 d, OR 1.14 (95% CI 1.02-1.28); Mortality by 28 d, OR 1.09 (95% CI 0.96-1.23); RRT, OR 0.9 (95% CI -0.9-2.7) Supplementary table 4: Summary table of RCTs examining the effect of dopamine vs. placebo for the treatment of AKI No. analyzed Baseline Intervention/Control Event rate Author Year Study (No randomized) Concomitant RR* Outcome Age kidney Setting Arm 1 Country duration medication (95% CI) Quality function Arm 1 Arm 2 Arm 1 Arm 2 (Arm 2) P value Critically Ill Patients Mortality Survival to ICU 67% 1.04 NS Fair discharge (64%) (0.89-1.22) (0.61) Survival to hospital Bellomo [9] 2000 161 163 57% 0.96 NS 63 SCr 183 μmol/l ICU nd Dopamine Placebo nd Fair discharge Australia (163) (165) (60%) (0.80-1.15) (0.66) 43% 1.06 Mortality nd Fair (40%) (0.82-1.37) RRT Bellomo [9] 2000 161 163 22% 0.89 NS RRT 63 SCr 183 μmol/l ICU nd Dopamine Placebo nd Fair Australia (163) (165) (25%) (0.60-1.32) (0.55) Annotations: * Calculated by ERT with raw data from original studies when available. When study reported only event rates, calculations were done using percentages. Supplementary table 5: Evidence profile of RCTs examining fenoldopam vs. control for the prevention of AKI Directness of Summary of findings # of studies Methodological Total N Consistency the evidence Other Outcome and quality of studies (treatment) across studies generalizability/ considerations Quality of evidence Qualitative and quantitative description of Importance study design per outcome applicability for outcome effect of outcome 1 RCT 300 Sparse No significant difference however single study Mortality No limitations N/A No uncertainty Moderate Critical (High) (150) (-1) in sepsis. Trend to less RRT (borderline benefit in the one 3 RCTs 653 No important Imprecision RRT No limitations No uncertainty Moderate study in sepsis patients and very low event Critical (High) (325) inconsistencies (-1) a rates in the two studies in CTS patients). 3 RCTs 653 No important Consistent benefit for kidney function in all three High AKI No limitations No uncertainty None High (High) (325) inconsistencies studies, but variable outcome definitions. (Crucial) Balance of potential benefits and harm Quality of overall evidence Benefit for prevention of AKI with fenoldopam, but major concerns about potential for harm from hypotension and tachycardia. High Annotations: a. Low event rates in CTS studies Supplementary table 6: Summary table of RCTs examining the effect of fenoldopam for the prevention of AKI No. analyzed Intervention/Control Event rate Author Year Baseline kidney Study (No randomized) Concomitant RR* Outcome Age Setting Arm 1 Country function duration medication (95%CI) Quality Arm 1 Arm 2 Arm 1 Arm 2 (Arm 2) P value CTS Patients RRT Caimmi [19] SCr 1.82 mg/dl 80 80 Conventional 0% 0.14 NS 5 d 70 CTS 5 d Fenoldopam nd Fair 2003 Italy GFR 51 ml/min (80) (80) maintenance (4%) (0.01-2.72) (>0.1) Cogliati [22] SCr 1.8 mg/dl 95 98 Normal 0% 0.06 Mean 13 d 70 CTS Mean 13 d Fenoldopam Per protocol 0.004 Good 2007 Italy GFR 40 ml/min (95) (98) saline (8%) (0.00-1.04) AKI ↑SCr to 1.5X Caimmi [19] SCr 1.82 mg/dl 80 80 Conventional 0% 0.02 70 CTS 5 d Fenoldopam nd <0.01 Fair basal 2003 Italy GFR 51 ml/min (80) (80) maintenance (31%) (0.00-0.32) ↑SCr to >2 mg/dl with Cogliati [22] SCr 1.8 mg/dl 95 98 Normal 13% 0.46 ∆SCr 70 CTS Mean 13 d Fenoldopam Per protocol 0.02 Good 2007 Italy GFR 40 ml/min (95) (98) saline (28%) (0.25-0.85) >0.7 mg/dl, 48 h Sepsis Patients Mortality Morelli [54] SCr 89.8 μmol/l 150 150 35% 0.79 NS Mean 8 d 58 Sepsis Mean 8 d Fenoldopam Placebo nd Good 2005 Italy GFR 81 ml/min (150) (150) (44%) (0.59-1.05) (0.1) RRT Morelli [54] SCr 89.8 μmol/l 150 150 7% 0.56 Mean 8 d 58 Sepsis Mean 8 d Fenoldopam Placebo nd 0.056 Good 2005 Italy GFR 81 ml/min (150) (150) (14%) (0.38-0.83) AKI ↑SCr >150 0.57 Morelli [54] SCr 89.8 μmol/l 150 150 19% μmol/l during 58 Sepsis Mean 8 d Fenoldopam Placebo nd (0.38-0.84) 0.006 Good 2005 Italy GFR 81 ml/min (150) (150) (34%) drug infusiona [p 0.005] Annotations * Calculated by ERT with raw data from original studies when available.