1. Acute Renal Failure aka Acute Kidney Injury Pouneh Nouri MD Georgetown University Hospital Division of Nephrology

2. Definition of Acute Kidney Injury (AKI) based on “Acute Kidney Injury Network” Stage Increase in Serum Creatinine Urine Output 1 1.5-2 times baseline OR 0.3 mg/dl increase from baseline <0.5 ml/kg/h for >6 h 2 2-3 times baseline <0.5 ml/kg/h for >12 h 3 3 times baseline OR 0.5 mg/dl increase if baseline>4mg/dl OR Any RRT given <0.3 ml/kg/h for >24 h OR Anuria for >12 h

3. RIFLE criteria for diagnosis of AKI based on The “Acute Dialysis Quality Initiative” Am J Kidney Dis. 2005 Dec;46(6):1038-48 Increase in S Cr Urine output R isk of renal injury I njury to the kidney F ailure of kidney function 0.3 mg/dl increase 2 X baseline 3 X baseline OR > 0.5 mg/dl increase if S Cr >=4 mg/dl < 0.5 ml/kg/hr for > 6 h < 0.5 ml/kg/hr for >12h Anuria for >12 h L oss of kidney function E nd-stage disease Persistent renal failure for > 4 weeks Persistent renal failure for > 3 months

8. Major Disease Categories Causing AKI Disease Category Incidence Prerenal azotemia caused by acute renal hypoperfusion 55-60% Intrinsic renal azotemia caused by acute diseases of renal parenchyma: -Large renal vessels dis. -Small renal vessels and glomerular dis. -ATN (ischemic and toxic) -Tubulo-interestitial dis. -Intratubular obstruccttion 35-40% *>90%* Postrenal azotemia caused by acute obstruction of the urinary tract <5%

13. Likelihood ratio (LR) of ATN vs pre-renal azotemia on the basis of the number of granular casts in urinary sediment Clin J Am Soc Nephrol 4:691-693, 2009 Granular casts/hpf LR for ATN LR for pre-renal 0 0.23 4.35 1-5 2.97 0.34 6-10 9.68 0.1

14. RBC cast Hyaline cast Granular cast Granular cast Granular cast WBC cast WBC cast Oval fat body and Hyaline cast

20. Results of individual RCTs comparing CRRT to IHD in AKI in ICU Study n n Primary endpoint Mortality Mortality Persistent RRT requirement CRRT IHD CRRT IHD CRRT IHD Mehta et al KI 2001 84 82 ICU mortality 59.5 41.5 14 7 Augustine et al AJKD 2004 40 40 In-hospital mortality 67.5 70 61.5 66.7 Uehlinger et al NDT 2005 70 55 In-hospital mortality 47 51 2.7 3.7 Vinsonneau et al Lancet 2006 175 184 60-day mortality 67.4 68.5 1.8 0 Lins et al NDT 2009 172 144 In-hospital mortality 58.1 62.5 16.9 25.5

22. Results of RCTs comparing benefits of the intensity of RRT (high vs low dose dialysis) * Veterans Administration/National Institute of Health Acute Renal Failure Trial Network Study Study n Low dose modality High dose modality Endpoint Results for low dose Results for high dose P Schiffl et al NEJM 2002 146 Thrice-weekly IHD Daily IHD 1-Mortality 2-Time to renal recovery 46% 16 days 28% 9 days Sig Ronco et al Lancet 2000 425 CVVH dose of 20 ml/kg/h CVVHDF dose of 35 or 45 ml/kg/h 90-day survival 34% 59% Sig Palvesky et al NEJM 2008* 1100 High dose : CRRT 35 ml/kg/h or SLED X 6/wk or IHD X 6/wk Low dose: CRRT 20 ml/kg/h or SLED X 3/wk or IHD X 3/wk 60-day mortality 51.8% 53.6% NS RENAL Clinical Trial (not published) 1500 CVVHDF 25 ml/kg/h CVVHDF 40 ml/kg/h 90-day Survival NS

56. Thank you!