1. acute renal failure … from basics to the latest advances Joel M. Topf, MD Clinical Nephrologist http://pbfluids.com

2. the house moment

3. Dr. Haas invented the first dialysis machine designed for humans and in 1928 he treated 6 patients. All of them died.

4. In 1943, Willem Kolff’s, working in Nazi occupied Netherlands created the second human dialysis machine. In 1943 he dialyzed his first patient, a young man with acute nephritis. In 1945, a 67-year-old woman in uremic coma presented to Dr Kolff.                 Regained consciousness after 11 hours of hemodialysis.       Dr. Haas

10. Same rise in creatinine. Same diagnosis: acute renal failure. Two completely different diseases. Two women. Same age. Same race.

16. R isk I njury F ailure L oss of function E nd-Stage Renal disease rifle criteria for stratifying arf

22. R isk : Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs I njury : Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs F ailure : Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr > 24 hrs or anuria for more than 12 hours L oss of function : Need for dialysis for more than 4 weeks E nd-Stage Renal disease : Need for dialysis for more than 3 months

24. Hospital Mortality >3x BL Cr Cr > 4

27. when Hoste looked at markers of severity of illness excluding the renal system: No survival difference between the 4 groups: • Lack of renal failure • Risk • Injury • Failure

28. RIFLE is dependent on creatinine. creatine is a functional marker of organ damage Functional markers: old and busted

29. biomarkers are foot prints of actual organ damage Biomarkers, new hotness

30. functional versus biomarkers Functional Marker Biomarker Liver damage Hypoalbuminemia Coagulopathy SGOT SGPT GGT

31. functional versus biomarkers Functional Marker Biomarker Liver damage Hypoalbuminemia Coagulopathy SGOT SGPT GGT Heart damage Hypotension Arrhythmia Troponin I Troponin T CK-MB

32. functional versus biomarkers Functional Marker Biomarker Liver damage Hypoalbuminemia Coagulopathy SGOT SGPT GGT Heart damage Hypotension Arrhythmia Troponin I Troponin T CK-MB Kidney damage Creatinine BUN Cystatin C KIM-1 NGAL

34. <0.5 0.4 0.2 0.1 0.3 0.5 0.7 0.9 Creatinine falls Creatinine rises Delta Creatinine (mg/dL)

35. candidates for a renal troponin:

42. differential diagnosis

44. Hou SH, Bushinsky DA, Wish JB. Am J Med 1983; 74: 243-8. Nash K, Hafeez A, Hou S. Am J Kidney Dis. 2002; 39: 930-6. Kaufman J, Dhakal M, Patel B, Et al. Am J Kidney Dis 1991; 17: 191-8.

45. Hou SH, Bushinsky DA, Wish JB. Am J Med 1983; 74: 243-8. Nash K, Hafeez A, Hou S. Am J Kidney Dis. 2002; 39: 930-6. Kaufman J, Dhakal M, Patel B, Et al. Am J Kidney Dis 1991; 17: 191-8.

46. N=103 N=256 N=389 Pascual J, Liano F. J Am Geriatr Soc 1998, 46: 1-5.

47. hospital acquired acute renal failure

48. hospital acquired acute renal failure

51. Pre-renal azotemia No BP, no pee pee

55. Excreted Na Filtered Na Fractional excretion of sodium:

56. Excreted Na = Urine Na x Urine Volume Calculating the Numerator

57. Filtered Na = Serum Na x GFR Calculating the Denominator GFR = Urine Cr x Urine Volume Serum Cr Filtered Na = Serum Na x UrCr x UrVol Serum Cr

58. Urine Na x Urine Volume Serum Na x UrCr x Urine Volume Serum Cr FENa = Excreted Na Filtered Na FENa = Urine Na Serum Na x UrCr Serum Cr FENa = Urine Na x Serum Cr Serum Na x UrCr FENa =

68. FENa FEUrea

69. therapy Renal replacement therapy Furosemide Dopamine Fenoldapam hANP (Anaritide)

70. renal replacement therapy

71. Dialysate Conventional Dialysis Diffusive Clearance 136 5.8 108 17 67 3.8 145 2 110 35 0 0

72. 80 mmol K 5.8 mmol/L = 13.8 liters Isolated Ultrafiltration: CHF Solutions Minimal clearance 136 5.8 108 17 67 3.8 136 5.8 108 17 67 3.8

73. Ultrafilter 3+ liters/hour Replace all ultrafiltrate with sterile fluid at ideal plasma concentrations CVVH Convective clearance 136 5.8 108 17 67 3.8 140 2 108 30 0 0 140 4 108 30 0 0

74. Post-filter replacement fluid CVVH Convective clearance

75. Pre-filter replacement fluid CVVH Convective clearance

76. CVVHDF Convective and Diffusive

77. high dose dialysis survival Severity of illness (CCARF Score) High dose Low dose

79. 20 mL/kg/hr 35 mL/kg/hr 45 mL/kg/hr Ronco C, Bellomo R, Hormea P, Et al. Lancet 2000; 355: 26-30.

81. odds ratio of death Schiffl, H. et al. N Engl J Med 2002;346:305-310 P=0.002 P=0.005 P=0.007 P=0.02

83. Ronco 425 CVVH 20/h vs. 35-45 ml/kg/h* Bouman 106 CVVH 20ml/kg/h* vs. 48 ml/kg/h Schiffl 160 Alternate day vs. daily hemodialysis Saudan 206 CVVH 25 ml/kg/h vs. CVVHDF 42 ml/kg/h Total (fixed effects) Total (random effects) 1 10 Odds ratio Study n treatment groups *For purposes of analysis the two high-dose arms in Ronco were combined, as were the two low-dose arms in Bouman. If these groups are removed the odds ratio is unchanged (1.94; P <0.001). Kellum J. Nature Clin Practice Nephrol 2007 3: 128-9.

86. interventions

88. results 563 enrolled in standard care 561 randomized to intensive therapy

92. This report currently should be viewed as the definitive study defining dialysis dosing in critically ill patients with AKI H. David Hume

93. … the patient dies from multi-organ failure while in exquisite electrolyte & fluid balance .

94. Fluid balance?

97. Worse fluid overload severity remained independently associated with mortality (OR, 1.03; 95% CI, 1.01-1.05). The relationship was satisfactorily linear and the OR suggests a 3% increase in mortality for each 1% increase in degree of fluid overload at CRRT initiation.

99. [in regards to the kidney] these excretory operations are incidental to the major task of keeping our internal environments in the ideal, balanced state . Homer Smith from Fish to Philosopher

115. P=0.235 P=0.163 P=0.068 P=0.048 P=0.015 P=0.036 P=0.022 Tumlin JA, Finkel KW, Murray PT, Et al. Am J Kidney Dis. 2005; 46:26-34.

116. Tumlin JA, Finkel KW, Murray PT, Et al. Am J Kidney Dis. 2005; 46:26-34.

118. Prophylaxis is a way to get around the problem of late diagnosis due to the lack of an established biomarker.

119. P=0.006 P=0.056 Fenoldapam Placebo

128. Done