1. Acute Kidney Dysfunction in the ICU Slide Sub-Title John A. Kellum, MD Director, Molecular Core Laboratory Associate Professor of Critical Care Medicine and Medicine Intensivist, Cardiothoracic and Liver Transplant ICUs The CRISMA Laboratory Critical Care Medicine School of Medicine Health Policy and Management Graduate School of Public Health University of Pittsburgh

5. RIFLE Criteria for Acute Kidney Dysfunction R isk I njury F ailure L oss E SRD Increased creatinine x 1.5 or GFR decrease >25% End Stage Renal Disease GFR Criteria* Urine Output Criteria UO <.3ml/kg/h x 24 hrs or anuria x 12 hrs UO <.5ml/kg/h x 12 hrs UO <.5ml/kg/h x 6 hrs Increased creatinine x 2 or GFR decrease >50% Increase creatinine x 3 or GFR dec >75% or creatinine  4mg/dl (Acute rise of  0.5 mg/dl) High Sensitivity High Specificity Persistent AKD** = complete loss of renal function > 4 weeks www.ADQI.net Oliguria Bellomo R, et al. Crit Care. 2004;8:R204–R212.

6. RIFLE Creatinine is expressed in mg/dL and (mcmol/L). AKD is classified according to the worst grade for each domain (creatinine or urine output). If baseline serum creatinine is abnormal, a smaller relative increase is required to reach “failure.” Bellomo R, et al. Crit Care. 2004;8:R204–R212. Baseline 0.5 (44) 1.0 (88) 1.5 (133) 2.0 (177) 2.5 (221) 3.0 (265) Risk 0.75 (66) 1.5 (133) 2.3 (200) 3.0 (265) 3.8 (332) --- Injury 1.0 (88) 2.0 (177) 3.0 (265) --- --- --- Failure 1.5 (133) 3.0 (265) 4.0 (350) 4.0 (350) 4.0 (350) 4.0 (350)

10. Types of Kidney Dysfunction Biochemical indices useful to distinguish a pre-renal from a renal ARF episode pre - renal renal osm u (mOsm/kg) > 500 < 400 Na u (mmol/L or meq/L) < 20 > 40 BUN/s creatinine > 20 < 10 u/s creatinine > 40 < 20 u/s osmolality > 1.5 > 1 FeNa (%)* < 1 > 2 ________________________________________________________________ * ( (u Na / s Na) / (u creat / s creat) ) X 100 u for urinary, s for serum, Fe = fractional excretion

12. Cellular Injury and Repair in acute tubular necrosis (ATN) * very few necrotic cells are observed from patients with ATN Propagation Inflammation Proliferation And Redifferentiation Normal Tubular Cells De- Differentiated Cells Apoptotic Cells Injured Cells Necrotic * Cells Exfoliation Into the Urine Recovery (rapid) Recovery (slow) Injury

13. Presence of AKD is Strongly Associated with Hospital Mortality After adjusting for differences in comorbidity, AKD was associated with a 5.5 times greater chance of death compared to matched controls without AKD. Levy et al. JAMA. 1996;275:1489-94 .

14. Metnitz et al. Intens Care Med. 2002 Need for Renal Replacement Therapy (RRT) is Strongly Associated with Hospital Mortality

15. Metnitz et al. Intens Care Med. 2002

19. Dopamine is not Effective Harm Benefit Kellum & Decker, Crit Care Med. 2001; 29:1526-1531. 0.1 1 10 Death All Studies Excludes Radio-contrast Heart Disease Only ARF Hemodialysis All Studies Excludes Radio-contrast Heart Disease Only Excludes Outliers All Studies Excludes Radio-contrast Heart Disease Only Excludes Outliers

29. Tepel et al. N Engl J Med.2000;343:180-184.

30. Birck et al. Lancet. 2003;362:598-603. NAC reduces the risk of AKD (increased creatinine) by 50%.

32. Does isotonic sodium bicarbonate work better than isotonic sodium chloride solution for prevention of AKD after radiocontrast? N=154 Merten et al. JAMA. 2004;291:(19).

36. Ronco et al. Lancet. 2000; 355:26-30. Cumulative Survival vs. Ultrafiltration Rate 100 90 80 70 60 50 40 30 20 10 0 Group 1(n=146) ( Uf = 20 ml/h/Kg) Group 2 (n=139) ( Uf = 35 ml/h/Kg) Group 3 (n=140) ( Uf = 45 ml/h/Kg) 41 % 57 % 58 % p < 0.001 p n.s. p < 0.001

37. Survival Time (Days) 50 40 30 20 10 0 1.0 .9 .8 .7 .6 .5 .4 .3 .2 .1 .0 Group 1 Group 3 Group 2 (p = 0.0007) (p = 0.0013) Ronco et al. Lancet. 2000; 355:26-30. Cumulative Proportion Survival

38. Adapted from Shiffl et al. N Engl J Med. 2002;346:305-10. Survival vs. Dialysis Dose In Intermittent Hemodialysis 100 90 80 70 60 50 40 30 20 10 0 3/wk HD wKT/V = 3.6 7/wk HD wKT/V = 7.4 54 % 72 %

39. Membrane Biocompatibility 1 1.37 1.46 * - Abstracts 0.5 2.0 698 Excluding Gastaldello 857 Combined 2000 159 Gastaldello 1999 160 Jorres 1998 153 Himmelfarb 1998 66 Albright * 1996 166 Neveu 1996 51 Assouad * 1995 57 Kurtal 1994 52 Schiffl Year N 1 st Author Subramanian et al. Kidney Int. 2002; 62:1819-23. Odds Ratios for Survival

40. Continuous vs. Intermittent RRT Insufficient evidence from published studies to determine which therapy is best. However, CRRT appears to be superior under most sets of assumptions. Kellum et al. Intens Care Med . 2002;28:29-37. Unadjusted severity threshold quality threshold all studies Adjusted quality raw quality wgt severity both q & s Treatment of x-overs* as CRRT excluded 0.2 0.6 1 1.4 Relative Risk of Death Favors CRRT Favors IRRT