The document discusses the history and development of acute renal failure treatment from the first dialysis machines in the 1920s to modern biomarkers and therapies. It covers key events and discoveries like Dr. Kolff's first patient surviving hemodialysis in 1943. Classification systems for acute renal failure like RIFLE are presented along with the limitations of creatinine as a marker. Biomarkers like KIM-1 and NGAL are proposed as more accurate indicators of kidney injury. Differential diagnosis and treatment options such as renal replacement therapy are also summarized.

1. acute renal failure … from basics to the latest advances Joel M. Topf, MD Clinical Nephrologist

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 the 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 SGOT SGPT GGT Hypoalbuminemia Coagulopathy Liver damage Biomarker Functional Marker

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

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

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:

40. differential diagnosis

42. 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.

43. 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.

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

45. hospital acquired acute renal failure

46. hospital acquired acute renal failure

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

52. Excreted Na Filtered Na Fractional excretion of sodium:

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

54. 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

55. 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 =

64. FENa FEUrea

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

66. renal replacement therapy

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

68. 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

69. 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

70. Post-filter replacement fluid CVVH Convective clearance

71. Pre-filter replacement fluid CVVH Convective clearance

72. CVVHDF Convective and Diffusive

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

75. 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.

77. 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

79. 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.

95. 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.

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

98. P=0.006 P=0.056 Fenoldapam Placebo

108. Done