ARF No ATN Data
Upcoming SlideShare
Loading in...5
×
 

ARF No ATN Data

on

  • 3,963 views

Good overview of acute renal failure but this was written before the most recent ATN data which negates one of the premises of the lectuer that higher doses of dialysis are beneficial in patients in ...

Good overview of acute renal failure but this was written before the most recent ATN data which negates one of the premises of the lectuer that higher doses of dialysis are beneficial in patients in ARF.

Statistics

Views

Total Views
3,963
Views on SlideShare
3,564
Embed Views
399

Actions

Likes
3
Downloads
237
Comments
0

5 Embeds 399

http://www.pbfluids.com 350
http://pbfluids.blogspot.com 39
http://www.slideshare.net 8
http://webcache.googleusercontent.com 1
https://www.linkedin.com 1

Accessibility

Upload Details

Uploaded via as Adobe PDF

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

ARF No ATN Data ARF No ATN Data Presentation Transcript

  • acute renal failure …from basics to the latest advances Joel M. Topf, MD Clinical Nephrologist
  • the house moment
  • Dr. Haas invented the first dialysis machine designed for humans and in 1928 he treated 6 patients. All of them died.
  • 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.   Dr. Haas In 1945, a 67-year-old woman in uremic coma presented to Dr Kolff. Regained consciousness after 11 hours of hemodialysis.
  •  Commonly quoted mortality of 70% is for dialysis requiring ICU patients  For hospital acquired ARF: 20%
  •  37 year old AA female  Multiple GSW  Prolonged hypotension  Aorta was cross clamped during exploratory laparotomy  Anuric x 18 hours  Cr from 0.8 to 2.2
  •  36 y.o. African American women with menorrhagia.  Has prolonged bleeding following fibroidectomy  Contrasted CT scan used to determine source of bleeding.  Cr rises from 0.8 to 2.2  Patient is non-oliguric
  • Two women. Same age. Same race. Same rise in creatinine. Same diagnosis: acute renal failure. Two completely different diseases.
  • definition of acute renal failure “Acute and sustained reduction in renal function.” 35 definitions
  • biochemical definitions Contrast nephropathy ARF is defined by a 0.5 mg/dL or 25% increase in serum creatinine
  • event driven definitions Dialysis dependent ARF is often used in retrospective cohorts  Easy to capture  Unambiguous  Important end-point
  • rifle criteria for stratifying arf R isk I njury F ailure L oss of function E nd-Stage Renal disease
  • R isk  Increase in Cr of 1.5-2.0 X baseline or  urine output < 0.5 mL/kg/hr for more than 6 hours. I njury F ailure L oss of function E nd-Stage Renal disease
  • R isk: Inc Cr 50-100% or U.O. < 0.5 mL/kg/hr for > 6 hrs I njury  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. F ailure L oss of function E nd-Stage Renal disease
  • 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  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. L oss of function E nd-Stage Renal disease
  • 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  persistent renal failure (i.e. need for dialysis) for more than 4 weeks. E nd-Stage Renal disease
  • 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  persistent renal failure (i.e. need for dialysis) for more than 3 months.
  • 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
  • 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.
  • >3x BL Cr Cr > 4 Hospital Mortality
  • 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
  • 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
  • RIFLE is dependent on creatinine. creatine is a functional marker of organ damage Functional markers: old and busted
  • biomarkers are foot prints of actual organ damage Biomarkers, new hotness
  • functional versus biomarkers Functional Marker Biomarker SGOT Hypoalbuminemia Liver damage Coagulopathy SGPT GGT
  • functional versus biomarkers Functional Marker Biomarker SGOT Hypoalbuminemia Liver damage Coagulopathy SGPT GGT Troponin I Hypotension Heart damage Arrhythmia Troponin T CK-MB
  • functional versus biomarkers Functional Marker Biomarker SGOT Hypoalbuminemia Liver damage Coagulopathy SGPT GGT Troponin I Hypotension Heart damage Arrhythmia Troponin T CK-MB Creatinine KIM-1 Kidney damage BUN NGAL Cystatin C
  • creatinine as a lagging indicator  4,118 Cardiac surgery patients  Prospectively looked at changes of creatinine 48 hours post-op on 30-day mortality  All odds ratios were controlled for 26 variables found to be significant predictors of mortality in univariate analysis
  • Creatinine falls Creatinine rises <0.5 0.4 0.2 0.1 0.3 0.5 0.7 0.9 Delta Creatinine (mg/dL)
  • candidates for a renal troponin:
  • candidates for a renal troponin: kidney injury molecule-1 (kim-1)  Transmembrane protein expressed 2.00 in the proximal tubule. 0.69  Expression is 0.34 increased 0.13 following ischemic damage  Can be found 12 hours after renal insult Han WH, Bailly V, Abichandani. Kidney Int 2002 62, 237–244. Liangos O, Han WK, Wald R. Abstract J Am Soc Nephrol 16: 318A, 2005.
  • candidates for a renal troponin: kidney injury molecule-1 (kim-1)  Transmembrane Time starts at aorta cross protein expressed clamp. Cr rose to 2.1. in the proximal tubule.  Expression is inc- reased following ischemic damage  Can be found 12 hours after renal insult Han WH, Bailly V, Abichandani. Kidney Int 2002 62, 237–244. Liangos O, Han WK, Wald R. Abstract J Am Soc Nephrol 16: 318A, 2005.
  • urinary neutrophil gelatinase- associated lipocalin (ngal)  Protein that is secreted  Prospective by the kidney in res- observational trial ponse to ischemic injury  81 adults going for  Early data in children Cardiac surgery showed nearly perfect  65 No AKI sensitivity and  1 died of MOF specificity  16 AKI (Risk or higher)  5 required CVVH  False positives with UTI  5 died of MOF Mishra J, Ma Q, Prada A. J Am Soc Nephrol 2003; 14: 2534-43. Wagener G, Jan M, K M. Anesthesia 2006; 105: 485-91.
  • differential diagnosis
  • 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
  • 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.
  • 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.
  • N=389 N=256 N=103 Pascual J, Liano F. J Am Geriatr Soc 1998, 46: 1-5.
  • hospital acquired acute renal failure
  • hospital acquired acute renal failure
  • Pre-renal azotemia No BP, no pee pee
  • no bp, no ARF pee Pre-renal pee  Properly functioning kidney, properly responding to a drop in systemic and renal perfusion RPF ulat ion au toreg GFR
  • differentiation of prerenal from intrinsic renal disease  Use of FENa  Fraction of filtered sodium which is excreted in the urine.  Patients with prerenal azotemia will be sodium avid and minimize renal excretion of sodium lowering the FENa below 1%
  • Fractional excretion of sodium: Excreted Na Filtered Na
  • Calculating the Numerator Excreted Na = Urine Na x Urine Volume
  • Calculating the Denominator Filtered Na = Serum Na x GFR GFR = Urine Cr x Urine Volume Serum Cr Filtered Na = Serum Na x UrCr x UrVol Serum Cr
  • Excreted Na FENa = Filtered Na Urine Na x Urine Volume FENa = Serum Na x UrCr x Urine Volume Serum Cr Urine Na FENa = Serum Na x UrCr Serum Cr Urine Na x Serum Cr FENa = Serum Na x UrCr
  • 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  Sr Na  Sr Cr Sr Cr x Ur Na FENa =  Ur Na Sr Na x Ur Cr  Ur Cr
  • FeNa. what is it good for?  The discriminator for differentiating between prerenal azotemia and ATN is 1%:  FENa < 1 indicates pre-renal  FENa > 1 indicates ATN azotemia Pre-renal ATN (oliguric and Pre-renal ATN (oliguric and azotemia non-oliguric) azotemia non-oliguric) FENa < 1 27 4 FENa > 1 3 51 FENa > 1 3 51 FENa < 1 27 4  Sensitivity: 90%  Sensitivity: 93%  Specificity: 93%  Specificity: 90% Miller, Schrier, Et al. Annals Int Med, 1978 Vol 89. p 47-50
  • Low FENa, Not pre-renal FENa False Positive  Pre-renal Azotemia  ATN tested too early  Contrast Nephropathy  ATN with CHF  Hemoglobinuric  ATN with cirrhosis nephropathy  ATN with severe burns  Myoglobinuric nephropathy  Non-oliguric acute renal  Acute rejection failure  Cyclosporin and Tacrolimus  Acute Glomerulonephritis toxicity*  ACEi in bilateral RAS or in  Hepatorenal syndrome RAS with solitary kidney  Acute interstitial nephritis  NSAID induced ARF
  • FeNa false negatives  Diuretics  Metabolic alkalosis
  • Low fractional excretion of sodium in acute renal failure Role of timing of the test and ischemia  Patients with a decreased FENa were tested earlier than those with an elevated FENa  1.7 days for the low FENa group  3.4 days for the high FENa group  70% of patients in the low FENa group had a subsequent FENa > 1%
  • 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 Cr x Ur Urea Na FEurea = FENa = Sr Na x UrUr Cr Urea x Cr Kaplan, Kohn. American J Nephrol, 1992; 12: 49-54.
  • 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 Carvounis, Sabeeha, Nisar, Et al. Kidney Int, 2002 Vol 62. p 2223-2229
  • FEUrea FENa
  • therapy Renal replacement therapy Furosemide Dopamine Fenoldapam hANP (Anaritide)
  • renal replacement therapy
  • Conventional Dialysis Diffusive Clearance 67 136 108 5.8 17 3.8 0 145 110 2 35 0 Dialysate
  • Isolated Ultrafiltration: CHF Solutions 80 mmol K = 13.8 liters 5.8 mmol/L Minimal clearance 67 136 108 5.8 17 3.8 67 136 108 5.8 17 3.8
  • CVVH Convective clearance 67 136 108 5.8 17 3.8 Ultrafilter 3+ liters/hour Replace all ultrafiltrate 0 with sterile fluid at ideal 140 108 plasma concentrations 4 2 30 0
  • CVVH Convective clearance Post-filter replacement fluid
  • CVVH Convective clearance Pre-filter replacement fluid
  • CVVHDF Convective and Diffusive
  • high dose dialysis High dose survival Low dose Severity of illness (CCARF Score)
  • 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
  • 45 mL/kg/hr 35 mL/kg/hr 20 mL/kg/hr Ronco C, Bellomo R, Hormea P, Et al. Lancet 2000; 355: 26-30.
  • Schiffl: daily dialysis versus three days/wk dialysis  160 patients P=0.01 P=0.001 Schiffl, H. et al. N Engl J Med 2002;346:305-310
  • odds ratio of death P=0.002 P=0.005 P=0.007 P=0.02 Schiffl, H. et al. N Engl J Med 2002;346:305-310
  • adding dialysis to CVVH  206 dialysis patients randomized to  CVVH 1-2.5 L/hr  CVVH plus 1-1.5 liters of dialysate (CVVHDF) P=0.03 P=0.008 Saudin P, Niederberger S, De Seigneux S, Et al. Kidney Int 2006; 70: 1312-7.
  • Study n treatment groups 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 *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.
  • future data  US trial: ATN  Primarily veterans hospital  Prospective randomized, multi-center trial  Dose finding study Conventional daily dialysis SLED CVVH CVVHD CVVHDF  Australian trial: RENAL
  • furosemide  Decreased activity of the ascending loop of Henle decreases renal oxygen demand by the kidney  Better align demand and supply in ischemia
  • Mehta’s trial of furosemide in arf  Retrospective review of ICU patients  Diuretic responsiveness determined survival Mehta, R. L. et al. JAMA 2002;288:2547-2553.
  • furosemide the rct  338 with dialysis dependent ARF  Randomized to high dose furosemide (2,000 mg/day) vs placebo  End-point length of dialysis  No improvement of survival, length of dialysis, number of dialysis sessions  Shorter time to 2 liters/day of urine output Cantarovich F, Rangoonwala B, Et al. Am J Kidney Dis 2004; 44: 402-9.
  • dopamine: still doesn’t work  In healthy volunteers low dose dopamine increases renal blood flow and induces diuresis Increased RBF  Patients in the intensive care unit do not respond this way. Increased urine
  • dopamine: still doesn’t work  In healthy volunteers low dose dopamine increases renal blood flow and induces diuresis  Patients in the intensive care unit do not respond this way.  RCT of 380 ICU patients with early renal failure ANZICS Clinical Trials Group. Lancet 2000;356:2139-47. Kellum JA, Decker JM.Crit Care 2001; 29:1526-31.
  • dopamine: still doesn’t work  In healthy volunteers low dose dopamine increases renal blood flow and induces diuresis  Patients in the intensive care unit do not respond this way.  RCT of 380 ICU patients with early renal failure  Meta-analysis of 58 studies and 2,149 patients ANZICS Clinical Trials Group. Lancet 2000;356:2139-47. Kellum JA, Decker JM.Crit Care 2001; 29:1526-31.
  • dopamine: the randomized controlled trial  328 ICU patients with SIRS  Early signs of renal failure  < 0.5 cc/kg/hr  Cr > 1.7 mg/dL without a prior history of renal disease  A rise in serum Cr of 0.9 mg/dL in less than 24 hours  The primary outcome was peak serum creatinine ANZICS Clinical Trials Group. Lancet 2000;356:2139-47.
  •  Secondary end points:  Furosemide dose 192 mg vs 268 mg p=0.39  Duration of mechanical ventilation 10 vs 11 p=0.63  Duration of ICU stay 13 vs 14 p=0.67  Survival to hospital discharge 92 vs 97 p=0.66
  • meta-analysis  Kellum and Decker searched MedLine (English and non-English literature) for every article on human trials with dopamine for the treatment or prevention of ARF from 1966 to 1999.  They included 58 studies with 2149 patients Kellum JA, Decker JM.Crit Care 2001; 29:1526-31.
  • A. Exclude radiocontrast studies B. Limited to heart studies C. Excludes studies in which had abnormal control groups or increased variance
  •  Dopamine increases cortical blood flow more than medullary blood flow  Cortical blood flow increases GFR  Cortical blood flow increases renal oxygen demand
  • complications of low-dose dopamine  Increase arrhythmias  Increased myocardial oxygen demand  Gut ischemia  Suppressed respiratory drive  Increased sensitivity to radiocontrast agents  Decreases in T-cell activity
  • dopamine 2.0: fenoldapam  Isolated DA-1 activity  Licensed as an IV anti-hypertensive  Increases medullary blood flow more than cortical blood flow  Improved oxygenation  Does not increase renal work
  • RCT of fenoldapam  155 patients randomized within 24 hours of 50% increase in Cr  Primary end-point incidence of need-for- dialysis and/or survival at 21 days  Fenoldapam or half normal saline for 72 hours  Protocolized definition of need-for-dialysis Tumlin JA, Finkel KW, Murray PT, Et al. Am J Kidney Dis. 2005; 46:26-34.
  • 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.
  • Tumlin JA, Finkel KW, Murray PT, Et al. Am J Kidney Dis. 2005; 46:26-34.
  • prophylactic fenoldapam in sepsis  300 patients with sepsis and no signs of AKI  Non-oliguric  Cr < 1.7  Randomized to prophylactic fenoldapam vs placebo
  • P=0.006 P=0.056 Fenoldapam Placebo
  • atrial natriuretic peptide  Recombinant Anaritide is therapeutic form  Dilates afferent arterioles  Improves GFR and urine output in animal models of ATN  Three high profile studies looked at using ANP in human AKI.
  • radiocontrast nephropathy  30 minutes of ANP before contrast  30 minutes of ANP after contrast  Cr > 1.8  Randomized to placebo or 1 of 3 doses of anaritide  Creatinine increase of 0.5 or 25% defined RCN Kurnik B, Allgren RL, Genter FC. Am J Kid Dis 1998; 31: 674-80.
  •  504 critically ill patients  Creatinine at randomization was 4.6  75% had a normal BL creatinine  24-hour infusion of Anaritide p=0.008 Allgren R, Manbury T, Rahman SN. N Eng J Med 1997; 336: 828-34.
  • oliguric follow-up. strict EBM.  222 oliguric patients  24-hour infusion of ANP P=0.51 P<0.001 P=0.22 Lewis J, Salem M, Chertow G. Am J Kid Dis 2000; 36: 767-74.
  • fixing everything that was wrong  Early treatment  50% increase in creatinine  Low dose anaritide  50 ng/kg/min vs 200 ng/kg/min  Anaritide run continuously until renal recovery or dialysis.  Previous studies used 24 hour infusion  Protocol defined indication for dialysis  UO < 0.5 cc/kg/hr  Pulmonary edema and for 3 hours FiO2 >0.8  Cr > 4.5  K>6.0 Swärd K, Valsson F, Odencrants P, Et al. Crit Care Med 2004; 32: 1310-5.
  •  N=61  Average Cr 2.3 Swärd K, Valsson F, Odencrants P, Et al. Crit Care Med 2004; 32: 1310-5.
  • summary  Prognosis is grim  We now have a validated, consensus definition  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
  • 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 a survival benefit  There is no proven benefit of one modality over another  Except peritoneal dialysis which has been proven to be inferior to CVVH  Dopamine doesn’t work  Fenoldapam and anaritide may have a role in reducing mortality from ARF.
  • Done