Acute Kidney Injury 2013

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Resident level lecture on AKI

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Acute Kidney Injury 2013

  1. 1. acute renal failure …from basics to the latest advances Joel M. Topf, MD Clinical Nephrologist http://pbfluids.com
  2. 2. the house moment
  3. 3. Dr. Haas invented the first dialysis machine designed for humans and in 1928 he treated 6 patients.
  4. 4. Dr. Haas invented the first dialysis machine designed for humans and in 1928 he treated 6 patients. All of them died. 
  5. 5. In 1943, Willem Kolff’s, working in Nazi occupied Netherlands created the second human dialysis machine from a washing machine, juice cans and sausage casings. In 1943 he dialyzed his first patient, a young man with acute nephritis.
  6. 6. In 1943, Willem Kolff’s, working in Nazi occupied Netherlands created the second human dialysis machine from a washing machine, juice cans and sausage casings. In 1943 he dialyzed his first patient, a young man with acute nephritis. 
  7. 7. In 1943, Willem Kolff’s, working in Nazi occupied Netherlands created the second human dialysis machine from a washing machine, juice cans and sausage casings. In 1943 he dialyzed his first patient, a young man with acute nephritis.  
  8. 8. In 1943, Willem Kolff’s, working in Nazi occupied Netherlands created the second human dialysis machine from a washing machine, juice cans and sausage casings. In 1943 he dialyzed his first patient, a young man with acute nephritis.    Dr. Haas
  9. 9. In 1943, Willem Kolff’s, working in Nazi occupied Netherlands created the second human dialysis machine from a washing machine, juice cans and sausage casings. In 1943 he dialyzed his first patient, a young man with acute nephritis.    Dr. Haas 0 for 22
  10. 10. In 1943, Willem Kolff’s, working in Nazi occupied Netherlands created the second human dialysis machine from a washing machine, juice cans and sausage casings. 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.    Dr. Haas 0 for 22
  11. 11. In 1943, Willem Kolff’s, working in Nazi occupied Netherlands created the second human dialysis machine from a washing machine, juice cans and sausage casings. 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.    Dr. Haas Regained consciousness after 11 hours of hemodialysis. 0 for 22
  12. 12. 0 20 40 60 80 Mortality(%) 75 45 Sepsis Other Causes Mortality by Etiology  Commonly quoted mortality of 70% is for dialysis requiring ICU patients  For hospital acquired ARF: 20%
  13. 13. Am J Med 2005 118, 827-832
  14. 14.  Patients with primary diagnosis of AKI have higher mortality when they are:  admitted on week-ends  admitted to smaller hospitals James et al. Weekend Hospital Admission, Acute Kidney Injury, and Mortality. Journal of the American Society of Nephrology (2010) vol. 21 (5) pp. 845-851
  15. 15. ICU associated AKI is characterized by a d e l a y b e t w e e n a d m i s s i o n a n d d e v e l o p m e n t o f acute renal injury
  16. 16. Risk Injury Failure Loss of function End-Stage Renal disease rifle criteria for stratifying arf
  17. 17. Risk  Increase in Cr of 1.5-2.0 X baseline or  urine output < 0.5 mL/kg/hr for more than 6 hours. Injury Failure Loss of function End-Stage Renal disease
  18. 18. Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs Injury  increase in Cr 2-3 X baseline (loss of 50% of GFR) or  urine output < 0.5 mL/kg/hr for more than 12 hours. Failure Loss of function End-Stage Renal disease
  19. 19. Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs Injury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs Failure  increase in Cr rises > 3X baseline Cr (loss of 75% of GFR) or  an increase in serum creatinine greater than 4 mg/dL, or  urine output < 0.3 mL/kg/hr for more than 24 hours or anuria for more than 12 hours. Loss of function End-Stage Renal disease
  20. 20. Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs Injury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs Failure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr > 24 hrs or anuria for more than 12 hours Loss of function  persistent renal failure (i.e. need for dialysis) for more than 4 weeks. End-Stage Renal disease
  21. 21. Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs Injury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs Failure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr > 24 hrs or anuria for more than 12 hours Loss of function: Need for dialysis for more than 4 weeks End-Stage Renal disease  persistent renal failure (i.e. need for dialysis) for more than 3 months.
  22. 22. Risk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs Injury: Inc Cr 100-200% or U.O. < 0.5 mL/kg/hr > 12 hrs Failure: Inc Cr > 200% or > 4 mg/dL or U.O. < 0.3 mL/kg/hr > 24 hrs or anuria for more than 12 hours Loss of function: Need for dialysis for more than 4 weeks End-Stage Renal disease : Need for dialysis for more than 3 months
  23. 23. nice criteria. do they work?  20,126 consecutive admissions to a university hospital  Excluded kids  Kidney transplant and dialysis patients  Patients admitted for < 24 hours  Using RIFLE:  Risk 9.1%  Injury 5.2%  Failure 3.7% Uchino S, Bellomo R, Goldsmith D. Crit Care Med 2006 Vol 34 1913-1917.
  24. 24. nice criteria. do they work?  20,126 consecutive admissions to a university hospital  Excluded kids  Kidney transplant and dialysis patients  Patients admitted for < 24 hours  Using RIFLE:  Risk 9.1%  Injury 5.2%  Failure 3.7% No Renal failure 82% Failure 4% Injury 5% Risk 9% Uchino S, Bellomo R, Goldsmith D. Crit Care Med 2006 Vol 34 1913-1917.
  25. 25. HospitalMortality
  26. 26. HospitalMortality
  27. 27. >3xBLCr Cr>4 HospitalMortality
  28. 28. nice criteria. do they work in the icu?  University of Pittsburgh has 7 ICUs  5,383 patients  Excluded dialysis  Subsequent admissions  Frequency of acute Kidney failure:  No AKD 1,766  Risk 670  Injury 1,436  Failure 1,511 Hoste E, Clermont G, Kersten A. Crit Care 2006 Vol 310
  29. 29. nice criteria. do they work in the icu?  University of Pittsburgh has 7 ICUs  5,383 patients  Excluded dialysis  Subsequent admissions  Frequency of acute Kidney failure:  No AKD 1,766  Risk 670  Injury 1,436  Failure 1,511 No Renal failure 33% Failure 28% Injury 27% Risk 12% Hoste E, Clermont G, Kersten A. Crit Care 2006 Vol 310
  30. 30. No AKI Risk Injury Failure 0 5 10 15 20 25 30 RRT LOS ICU LOS Mortality
  31. 31. No AKI Risk Injury Failure 0 5 10 15 20 25 30 RRT LOS ICU LOS Mortality
  32. 32. No AKI Risk Injury Failure 0 5 10 15 20 25 30 RRT LOS ICU LOS Mortality
  33. 33. AKIN criteria  refinement of RIFLE criteria  smaller change in Cr 0.3  time constraint of 48 hours for the diagnosis of AKI  anyone requiring dialysis is stage 3 AKI
  34. 34. RIFLE v AKIN RIFLERIFLE R Cr increased by 50-100% I Cr increased by 100-200% F Cr increased by more than 200% or Cr > 4 L Need for dialysis for > 4 weeks E Need for dialysis for > 3 months
  35. 35. RIFLE v AKIN RIFLERIFLE R Cr increased by 50-100% I Cr increased by 100-200% F Cr increased by more than 200% or Cr > 4 L E
  36. 36. RIFLE v AKIN RIFLERIFLE AKINAKIN R Cr increased by 50-100% 1 Cr increased by 0.3 or 50-100% I Cr increased by 100-200% 2 Cr increased by 100-200% F Cr increased by more than 200% or Cr > 4 3 Cr increased by more than 200%, Cr > 4, or renal replacement therapyL Cr increased by more than 200%, Cr > 4, or renal replacement therapy E
  37. 37. AKIN vs RIFLE 120,123 critically ill patients in 57 ICUs in New Zealand and Australia
  38. 38. AKIN vs RIFLE 120,123 critically ill patients in 57 ICUs in New Zealand and Australia 64% 16% 14% 6% RIFLE 63% 18% 10% 9% AKIN None Risk / 1 Injury / 2 Failure / 3
  39. 39. AKIN vs RIFLE 120,123 critically ill patients in 57 ICUs in New Zealand and Australia 64% 16% 14% 6% RIFLE 63% 18% 10% 9% AKIN None Risk / 1 Injury / 2 Failure / 3 2.24 3.95 5.13 2.45 4.23 5.22 Risk / 1 Injury / 2 Failure / 3 mortality odds ratio vs no AKI
  40. 40. oliguria: sensitive or specific?  oliguria is a biomarker of ARF  Used in the definition of RIFLE and AKIN  How good is it at predicting AKICreatinine
  41. 41.  ICU patients and tracked hourly urine outputs  oliguria: <0.5 ml/kg/hr  primary outcome: how predictive was oliguria for subsequent AKI as defined by creatinine  239 patients, 723 days, 23 cases of hospital acquired AKI
  42. 42. duration of oliguria AKI the next day No AKI next day None 5 443 ≥1 hour 18 257 ≥2 hours 15 194 ≥3 hours 13 125 ≥4 hours 12 95 ≥5 hours 7 75 ≥6 hours 5 50 ≥12 hours 4 9
  43. 43. duration of oliguria AKI the next day No AKI next day None 5 443 ≥1 hour 18 257 ≥2 hours 15 194 ≥3 hours 13 125 ≥4 hours 12 95 ≥5 hours 7 75 ≥6 hours 5 50 ≥12 hours 4 9
  44. 44. duration of oliguria AKI the next day No AKI next day None 5 443 ≥1 hour 18 257 ≥2 hours 15 194 ≥3 hours 13 125 ≥4 hours 12 95 ≥5 hours 7 75 ≥6 hours 5 50 ≥12 hours 4 9
  45. 45. duration of oliguria AKI the next day No AKI next day None 5 443 ≥1 hour 18 257 ≥2 hours 15 194 ≥3 hours 13 125 ≥4 hours 12 95 ≥5 hours 7 75 ≥6 hours 5 50 ≥12 hours 4 9
  46. 46. ICU associated AKI is characterized by a d e l a y b e t w e e n a d m i s s i o n a n d d e v e l o p m e n t o f acute renal injury
  47. 47. 4"days" 1"day"
  48. 48. N=29,269
  49. 49. N=29,269 AKI 1,738 (5.7%)
  50. 50. N=29,269 AKI 1,738 (5.7%)
  51. 51. T h i s d e l a y i n t h e development of AKI is an opportunity.
  52. 52. T h i s d e l a y i n t h e development of AKI is an opportunity. Often AKI is the result of a second hit. Don’t hit your patient.
  53. 53. risk factors for AKI  CKD  Age >75  Peripheral vascular disease  Heart failure  Liver disease  Diabetes  Nephrotoxins  NSAIDs  Aminoglycoseide  Hypotension  Hypovolemia  Cardiac disease  Iatrogenic  Sepsis
  54. 54. risk factors for AKI  CKD  Age >75  Peripheral vascular disease  Heart failure  Liver disease  Diabetes  Nephrotoxins  NSAIDs  Aminoglycoseide  Hypotension  Hypovolemia  Cardiac disease  Iatrogenic  Sepsis
  55. 55. etiologies of arf  Seventy percent have concurrent oliguria  < 400 mL/day  < 0.5 mL/kg/hr in children  < 1 mL/kg/hr in infants  Complicates 5-7% of hospitalizations
  56. 56. Community acquired 49.7% Hospital acquired 50.3% 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.
  57. 57. 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.
  58. 58. hospital acquired acute renal failure Sepsis 7% Other 2% CHF 4% Unknown 3% Other 7% Obstruction 2% Hypotension 11% Volume Contraction 21% Post-Op 15% Contrast 11% Medication 16%
  59. 59. hospital acquired acute renal failure
  60. 60. differentiation of prerenal from intrinsic renal disease
  61. 61. Excreted Na
  62. 62. Excreted Na Filtered Na
  63. 63. Excreted Na Filtered Na Fractional excretion of sodium:
  64. 64. Excreted Na = Urine Na x Urine Volume Calculating the Numerator
  65. 65. Calculating the Denominator
  66. 66. Calculating the Denominator Filtered Na = Serum Na x GFR
  67. 67. Calculating the Denominator GFR = Urine Cr x Urine Volume Serum Cr Filtered Na = Serum Na x GFR
  68. 68. Calculating the Denominator GFR = Urine Cr x Urine Volume Serum Cr Filtered Na = Serum Na x GFR Filtered Na = Serum Na x UrCr x UrVol Serum Cr
  69. 69. Excreted Na Filtered Na FENa =
  70. 70. Excreted Na Filtered Na FENa = FENa =
  71. 71. Excreted Na Filtered Na FENa = Urine Na x Urine Volume FENa =
  72. 72. Excreted Na Filtered Na FENa = Urine Na x Urine Volume Serum Na x UrCr x Urine Volume Serum Cr FENa =
  73. 73. Excreted Na Filtered Na FENa = Urine Na x Urine Volume Serum Na x UrCr x Urine Volume Serum Cr FENa =
  74. 74. Excreted Na Filtered Na FENa = Urine Na x Urine Volume Serum Na x UrCr x Urine Volume Serum Cr FENa = Urine Na Serum Na x UrCr Serum Cr FENa =
  75. 75. Excreted Na Filtered Na FENa = Urine Na x Urine Volume Serum Na x UrCr x Urine Volume Serum Cr FENa = Urine Na Serum Na x UrCr Serum Cr FENa = Urine Na x Serum Cr Serum Na x UrCr FENa =
  76. 76. FENa the easy way
  77. 77. FENa the easy way  FENa is a small number 0.1% to 3%
  78. 78. FENa the easy way  FENa is a small number 0.1% to 3%  So the calculation will be 0.001-0.03 prior to converting to percent by X 100
  79. 79. FENa the easy way  FENa is a small number 0.1% to 3%  So the calculation will be 0.001-0.03 prior to converting to percent by X 100  So make the fraction small by putting the small numbers over the big numbers
  80. 80.  Sr Na FENa the easy way  FENa is a small number 0.1% to 3%  So the calculation will be 0.001-0.03 prior to converting to percent by X 100  So make the fraction small by putting the small numbers over the big numbers
  81. 81.  Sr Na Sr Na FENa the easy way  FENa is a small number 0.1% to 3%  So the calculation will be 0.001-0.03 prior to converting to percent by X 100  So make the fraction small by putting the small numbers over the big numbers
  82. 82.  Sr Na  Sr Cr Sr Na FENa the easy way  FENa is a small number 0.1% to 3%  So the calculation will be 0.001-0.03 prior to converting to percent by X 100  So make the fraction small by putting the small numbers over the big numbers
  83. 83.  Sr Na  Sr Cr Sr Na Sr Cr FENa the easy way  FENa is a small number 0.1% to 3%  So the calculation will be 0.001-0.03 prior to converting to percent by X 100  So make the fraction small by putting the small numbers over the big numbers
  84. 84.  Sr Na  Ur Na  Sr Cr Sr Na Sr Cr FENa the easy way  FENa is a small number 0.1% to 3%  So the calculation will be 0.001-0.03 prior to converting to percent by X 100  So make the fraction small by putting the small numbers over the big numbers
  85. 85.  Sr Na  Ur Na  Sr Cr Sr Na Sr Cr x Ur Na FENa the easy way  FENa is a small number 0.1% to 3%  So the calculation will be 0.001-0.03 prior to converting to percent by X 100  So make the fraction small by putting the small numbers over the big numbers
  86. 86.  Sr Na  Ur Na  Ur Cr  Sr Cr Sr Na Sr Cr x Ur Na FENa the easy way  FENa is a small number 0.1% to 3%  So the calculation will be 0.001-0.03 prior to converting to percent by X 100  So make the fraction small by putting the small numbers over the big numbers
  87. 87.  Sr Na  Ur Na  Ur Cr  Sr Cr Sr Na Sr Cr x Ur Na x Ur Cr FENa = FENa the easy way  FENa is a small number 0.1% to 3%  So the calculation will be 0.001-0.03 prior to converting to percent by X 100  So make the fraction small by putting the small numbers over the big numbers
  88. 88. Why is the feNa high in ATN  Normally tubules reabsorb 98-99% of the filtered sodium
  89. 89. serum Na x GFR x minutes in a day urinary Na excretion Why is the feNa high in ATN  Normally tubules reabsorb 98-99% of the filtered sodium
  90. 90. Why is the feNa high in ATN  Normally tubules reabsorb 98-99% of the filtered sodium 140 x 0.1 x 1440 180
  91. 91. Why is the feNa high in ATN  Normally tubules reabsorb 98-99% of the filtered sodium 20160 180
  92. 92. Why is the feNa high in ATN  Normally tubules reabsorb 98-99% of the filtered sodium 0.8%
  93. 93. Why is the feNa high in ATN  Normally tubules reabsorb 98-99% of the filtered sodium 0.8%  So does ATN cause the tubules to fail to reabsorb the 99%?
  94. 94. Why is the feNa high in ATN  Normally tubules reabsorb 98-99% of the filtered sodium 0.8%  So does ATN cause the tubules to fail to reabsorb the 99%? NO
  95. 95. false positive FeNa  Contrast nephropathy  Acute glomerulonephritis  ATN with heart failure  ATN with burns  ATN with cirrhosis
  96. 96.  Contrast nephropathy  Acute glomerulonephritis  ATN with heart failure  ATN with burns  ATN with cirrhosis Low FeNa not pre-renal
  97. 97.  Contrast nephropathy  Acute glomerulonephritis  ATN with heart failure  ATN with burns  ATN with cirrhosis Low FeNa not pre-renal
  98. 98.  Contrast nephropathy  Acute glomerulonephritis  ATN with heart failure  ATN with burns  ATN with cirrhosis Low FeNa not pre-renal these are cases of ATN where the tubules effectively hold on to sodium
  99. 99. Why is the feNa high in ATN  Normally tubules reabsorb 98-99% of the filtered sodium but now the GFR is 30 not 100  The fena reflects the behavior of the tubules that are undamaged. Tubules affected by ischemia have a GFR of zero.
  100. 100. serum Na x GFR x minutes in a day urinary Na excretion Why is the feNa high in ATN  Normally tubules reabsorb 98-99% of the filtered sodium but now the GFR is 30 not 100  The fena reflects the behavior of the tubules that are undamaged. Tubules affected by ischemia have a GFR of zero.
  101. 101. Why is the feNa high in ATN 140 x 0.03 x 1440 180  Normally tubules reabsorb 98-99% of the filtered sodium but now the GFR is 30 not 100  The fena reflects the behavior of the tubules that are undamaged. Tubules affected by ischemia have a GFR of zero.
  102. 102. Why is the feNa high in ATN 6048 180  Normally tubules reabsorb 98-99% of the filtered sodium but now the GFR is 30 not 100  The fena reflects the behavior of the tubules that are undamaged. Tubules affected by ischemia have a GFR of zero.
  103. 103. Why is the feNa high in ATN 2.9%  Normally tubules reabsorb 98-99% of the filtered sodium but now the GFR is 30 not 100  The fena reflects the behavior of the tubules that are undamaged. Tubules affected by ischemia have a GFR of zero.
  104. 104. Acute renal success  GFR is normally 100 mL/min  Total plasma volume is only 3 liters  without massive fluid reabsorption, 30 minutes to filter all the plasma
  105. 105. Acute renal success  GFR is normally 100 mL/min  Total plasma volume is only 3 liters  without massive fluid reabsorption, 30 minutes to filter all the plasma
  106. 106. Acute renal success  GFR is normally 100 mL/min  Total plasma volume is only 3 liters  without massive fluid reabsorption, 30 minutes to filter all the plasma
  107. 107. Acute renal success  GFR is normally 100 mL/min  Total plasma volume is only 3 liters  without massive fluid reabsorption, 30 minutes to filter all the plasma Tubuloglomerular feedback
  108. 108. Kaplan, Kohn. American J Nephrol, 1992; 12: 49-54. fractional excretion of urea  Based on the physiologic increase in urea reabsorption with pre-renal azotemia  Normal FE Urea is 50-65% in well hydrated individuals  In prerenal azotemia this falls below 35%  Not affected by diuretics Sr Na Sr Cr x Ur Na x Ur Cr FENa =
  109. 109. Kaplan, Kohn. American J Nephrol, 1992; 12: 49-54. fractional excretion of urea  Based on the physiologic increase in urea reabsorption with pre-renal azotemia  Normal FE Urea is 50-65% in well hydrated individuals  In prerenal azotemia this falls below 35%  Not affected by diuretics Sr Urea Sr Cr x Ur Urea x Ur Cr FEurea =
  110. 110. Kaplan, Kohn. American J Nephrol, 1992; 12: 49-54. fractional excretion of urea  Based on the physiologic increase in urea reabsorption with pre-renal azotemia  Normal FE Urea is 50-65% in well hydrated individuals  In prerenal azotemia this falls below 35%  Not affected by diuretics Sr Urea Sr Cr x Ur Urea x Ur Cr FEurea =
  111. 111. Carvounis, Sabeeha, Nisar, Et al. Kidney Int, 2002 Vol 62. p 2223-2229 FEurea in the differential diagnosis of atn  102 patients with ARF  Gold standard was consultants full analysis and retrospective analysis of response to treatment.  Divided the cases into:  ATN  Prerenal without diuretic  Prerenal treated with diuretics
  112. 112. 0 25 50 75 100 Sensitivity(%) 92 50 91 90 Pre-Renal, No diuretics Pre-Renal, Diuretics FENa FEUrea
  113. 113. FENa FEUrea
  114. 114. outcomes Nephrology Dialysis Transplantation 23 2235-41, 2008 Clin J Am Soc Nephrol 3: 881-886, 2008
  115. 115. outcomes Nephrology Dialysis Transplantation 23 2235-41, 2008 Clin J Am Soc Nephrol 3: 881-886, 2008
  116. 116. outcomes Nephrology Dialysis Transplantation 23 2235-41, 2008 Clin J Am Soc Nephrol 3: 881-886, 2008
  117. 117. Acute kidney injury as a cause of CKD  3,679 diabetic veterans  baseline creatinine 1.1, average age 61  primary outcome: development of CKD 4  secondary outcome: all-cause mortality  1,822 hospitalized  530 developed AKI at least once  88% AKIN 1  12% AKIN 2, 3
  118. 118.  39,805 Kaiser Permanente  Hospitalized 1996-2003  all had pre-hospitalization GFR <45  among those who developed ARF (50% increase in Cr and dialysis)  26% died in the hospital  among survivors:  GFR 30-44 42% required permanent dialysis within a month of discharge  GFR 15-29 63% required permanent dialysis within a month of discharge
  119. 119. 26% 5% 20% 49% ARF in hospital Death in Hosp Died after d/c Alive, No dialysis ESRD 5% 4% 90% 2% No ARF in hospital
  120. 120. 34.7% 27.6% 28.4% 45.2% 14.4% 77.0% Death during Hospital ESRD after D/C GFR 30-44 GFR 15-29 GFR <15
  121. 121. even the lucky ones, not so lucky Survivors of ARF, not dialysis dependent No ARF dialysis-freesurvival
  122. 122. used to be... No dialysis. No foul.
  123. 123. Acute renal failure is a risk factor for progression of CKD Acute renal failure is a risk factor for progression of CKD
  124. 124. therapy Internist management Patient empowerment Renal replacement therapy
  125. 125. risk factors for AKI  CKD  Age >75  Peripheral vascular disease  Heart failure  Liver disease  Diabetes  Nephrotoxins  NSAIDs  Aminoglycoseide  Hypotension  Hypovolemia  Cardiac disease  Iatrogenic  Sepsis
  126. 126. risk factors for AKI  CKD  Age >75  Peripheral vascular disease  Heart failure  Liver disease  Diabetes  Nephrotoxins  NSAIDs  Aminoglycoseide  Hypotension  Hypovolemia  Cardiac disease  Iatrogenic  Sepsis
  127. 127. Internist management  Monitor I’s and O’s, daily weights  Frequent labs  BMP, phosphorous, albumin, U/A  Consult nephrology  Avoid hypotension  Dose adjust for renal failure  Follow-up after d/c for high risk of CKD  Avoid  Iodinated contrast  Aminoglycosides  ACEi/ARB  Thoughtful fluid management
  128. 128. risk factors for AKI  CKD  Age >75  Peripheral vascular disease  Heart failure  Liver disease  Diabetes  Nephrotoxins  NSAIDs  Aminoglycoseide  Hypotension  Hypovolemia  Cardiac disease  Iatrogenic  Sepsis
  129. 129. risk factors for AKI  CKD  Age >75  Peripheral vascular disease  Heart failure  Liver disease  Diabetes  Nephrotoxins  NSAIDs  Aminoglycoseide  Hypotension  Hypovolemia  Cardiac disease  Iatrogenic  Sepsis
  130. 130. Patient empowerment  talk to patients about what to do if they become acutely ill  increase fluid intake  decrease diuretics  monitor blood pressure
  131. 131. renal replacement therapy
  132. 132. Dialysate 140 5.8 108 17 76 7.8 145 2 110 35 0 0 Conventional Dialysis: combination of diffusive and convective Clearance 140 5.8 108 17 67 3.8 Blood Ultra-filtrate
  133. 133. Dialysate 140 5.8 108 17 76 7.8 145 2 110 35 0 0 Conventional Dialysis: combination of diffusive and convective Clearance 140 5.8 108 17 67 3.8 Blood Ultra-filtrate
  134. 134. 136 5.8 108 17 67 3.8 Isolated Ultrafiltration: CHF Solutions Minimal clearance
  135. 135. 136 5.8 108 17 67 3.8 136 5.8 108 17 67 3.8 Isolated Ultrafiltration: CHF Solutions Minimal clearance
  136. 136. 136 5.8 108 17 67 3.8 136 5.8 108 17 67 3.8 80 mmol KIsolated Ultrafiltration: CHF Solutions Minimal clearance
  137. 137. 136 5.8 108 17 67 3.8 136 5.8 108 17 67 3.8 80 mmol K 5.8 mmol/L Isolated Ultrafiltration: CHF Solutions Minimal clearance
  138. 138. 136 5.8 108 17 67 3.8 136 5.8 108 17 67 3.8 80 mmol K 5.8 mmol/L = 13.8 litersIsolated Ultrafiltration: CHF Solutions Minimal clearance
  139. 139. Ultrafilter 3+ liters/hour Replace all ultrafiltrate with sterile fluid at ideal plasma concentrations 136 5.8 108 17 67 3.8 140 2 108 30 0 0 CVVH Convective clearance
  140. 140. Ultrafilter 3+ liters/hour Replace all ultrafiltrate with sterile fluid at ideal plasma concentrations 136 5.8 108 17 67 3.8 140 4 108 30 0 0 CVVH Convective clearance
  141. 141. Post-filter replacement fluid CVVH Convective clearance
  142. 142. Pre-filter replacement fluid CVVH Convective clearance
  143. 143. CVVHDF Convective and Diffusive
  144. 144. high dose dialysis survival Severity of illness (CCARF Score)
  145. 145. high dose dialysis survival Severity of illness (CCARF Score)
  146. 146. high dose dialysis survival Severity of illness (CCARF Score) Low dose
  147. 147. high dose dialysis survival Severity of illness (CCARF Score) High dose Low dose
  148. 148. high dose dialysis survival Severity of illness (CCARF Score) High dose Low dose
  149. 149. high dose dialysis survival Severity of illness (CCARF Score) High dose Low dose
  150. 150. high dose dialysis survival Severity of illness (CCARF Score) High dose Low dose
  151. 151. Ronco’s landmark dialysis dose study  425 patients with dialysis dependent acute renal failure were randomized to one of three doses of CVVH  20 mL/kg/hr of effluent  35 mL/kg/hr  45 mL/kg/hr
  152. 152. 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.
  153. 153. 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.
  154. 154. 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.
  155. 155. ATN trial  US trial  Prospective randomized, multi-center trial  27 institutions  primarily veterans hospitals  Dose finding study, modality agnostic  Conventional dialysis  SLED  CVVH  CVVHD  CVVHDF
  156. 156. interventions
  157. 157. endpoint  Primary Endpoint: All-cause mortality at day 60.  Secondary endpoints:  In-hospital death  Recovery of renal function (CrCl>20) defined as complete if Cr was <0.5 over the baseline  Duration of renal replacement therapy  Dialysis free at 60 days  Duration of ICU stay  Return to previous home at day 60
  158. 158. results
  159. 159. results 563 enrolled in standard care 561 randomized to intensive therapy
  160. 160.  60% sepsis  80% vented  Apache II score 26 predicted mortality 55%  BUN at initiation of RRT 65  half in the MICU half in the SICU
  161. 161. This report currently should be viewed as the definitive study defining dialysis dosing in critically ill patients with AKI H. David Hume
  162. 162. …the patient dies from multi-organ failure while in exquisite electrolyte & fluid balance.
  163. 163. Fluid balance?
  164. 164. Fluid balance?
  165. 165.  Patients stratified by net fluid gain from admission to initiation of CRT Fluid in – fluid out ICU admit weight X 100
  166. 166.  longer ICU stay  higher mortality  more multi-organ dysfunction  more likely to be intubated  more inotropes  more sepsis  higher PRISM score More fluid. More sick.
  167. 167. 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.
  168. 168.  80 kg adult  Is and Os: 2,400 mL in (100 mL/hr) and 1,600 mL of urine (67 mL/hr)  Positive balance of 800 mL. If after 3 days the patient becomes oliguric with 200 mL of urine output for two days (2,200 mL positive per day) before initiating CRT.  That patient would be up 6,800 mL or 8% of bodyweight  24% increase in mortality compared to someone with matched ins and outs
  169. 169.  observational data from SOAP study of ICU care in Europe  198 ICUs  24 countries  147 patients  1120 had AKI  ARF defined as a Cr >3.5 or urine output < 500 mL
  170. 170. Moreover, this would suggest that prevention or management of fluid overload is evolving as a primary trigger/indicator for extra-corporeal fluid removal, and this may be independent of dose delivery or solute clearance. Critical Care 2008, 12:169
  171. 171. summary  Prognosis is grim  We have two validated, consensus definitions  R isk  I njury  F ailure  L oss of function  E srd  Outpatient and inpatient acquired ARF differ in etiology  Hospital acquired disease is your fault  AKIN  Stage 1  Stage 2  Stage 3
  172. 172. summary  FE of Urea is a validated way to separate pre-renal from AKI even in the presence of diuretics  Use of high dose dialysis regardless of methodology offers no survival benefit  Do not fluid overload your patient  Dopamine doesn’t work
  173. 173. Acute kidney injury is not a specialist’s emergency; it is seen commonly in acute medicine and, as such, it is essential that all physicians have the confidence and skills to identify and manage it.
  174. 174. Done

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