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02 Radhakrishnan   Acute Renal Failure Update
 

02 Radhakrishnan Acute Renal Failure Update

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    02 Radhakrishnan   Acute Renal Failure Update 02 Radhakrishnan Acute Renal Failure Update Presentation Transcript

    • Acute Renal Failure An Update Jai Radhakrishnan, MD, MS, FASN, FACC Associate Professor of Clinical Medicine Columbia University
    • Objectives Epidemiology of ARF Diagnostic workup Specific syndromes of ARF Treatment and Prevention
    • ARF-Definitions Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group Crit Care. 2004 Aug;8(4):R204
    • Changes in mortality in patients with acute renal failure over 47 years Ympa YP Am J Med. 2005 Aug;118(8):827-32.
    • Etiology of ARF Pre-renal (hemodynamic) Intra-Renal (parenchymal) Post-renal (obstructive)
    • ARF: Pre-renal Volume Depletion Prostaglandins Angiotensin-II Cardiac Redistribution Hepatorenal syndrome NSAIDS ACE-inhibitors
    • Hepatorenal Syndrome: Diagnostic Criteria MAJOR CRITERIA: Chronic/Acute liver disease with advanced hepatic failure and portal hypertension Low GFR (Creatinine>1.5mg/dL or CrCl<40ml/min) Absence of shock, bacterial infection, nephrotoxin, GI /renal fluid losses No sustained renal improvement after withdrawing diuretics and volume expansion (1.5 L NS) Proteinuria<500mg/d and renal usg without obstruction or parenchymal abnormality MINOR CRITERIA Urine Volume <500ml/day Urine Na <10meq/L Urine RBC<50/HPF Serum Na <130meq/L Hepatology. 1996 Jan;23(1):164-76
    • Efferent and Afferent Arterioles of Rabbit 100 100 AVP AVP % Reduction in Lumen Diameter 90 90 NE NE 80 80 70 70 60 60 50 50 40 40 30 30 20 20 10 10 0 0 -14 -13 -12 -11 -10 -9 -8 -7 -6 -5 -14 -13 -12 -11 -10 -9 -8 -7 -6 -5 Agonist (Log M) Agonist (Log M) Efferent Afferent Edwards AJP 1989
    • Terlipressin +/- Albumin In HRS Hepatology 36 (2002), pp. 941–948
    • Hepatorenal Syndrome Type I: Vasopressin in One Patient AVP SPA 120 120 SBP 100 100 SBP (mm Hg) (mm Hg) 80 80 60 60 UO 40 40 UO (cc/h) (cc/h) 20 20 0 0 -6 -4 -2 0 2 4 6 8 Time (hrs)
    • Diclofenac Residues as the Cause of Vulture population Decline in Pakistan Nature. 2004 Feb 12;427(6975):
    • ARF: Post-renal Consider obstruction in every patient with ARF. Sites of obstruction leading to ARF: Bladder neck obstruction Bilateral ureters Urine volume variable. Renal USG or Bladder catheterization.
    • ARF: Intra-Renal VASCULAR GLOMERULAR Vascular occlusion Acute/Rapidly progressive Atheroembolic glomerulonephritis disease Thrombotic microangiopathy TUBULAR Crystal INTERSTITIAL ATN Interstitial nephritis
    • Atheroembolic disease ARF precipitated by angiography Often eosinophilia and low complement Multi-organ dysfunction, livedo reticularis, blue toes Generally irreversible
    • Acute Interstitial Nephritis Triad of fever, skin rash and eosinophilia Eosinophiluria Drugs: penicillin, cephalosporins, diuretics, NSAIDS, dilantin Usually completely reversible upon withdrawing drug ?Glucocorticoids
    • Rapidly Progressive Glomerulonephritis ETIOLOGY Immune complex GN: -post infectious,SLE, IgAN, SBE, cryoglobulinemia Anti GBM antibody disease Vasculitis: -Wegener’s, microscopic PAN, idiopathic crescentic GN DIAGNOSTIC CLUES Systemic findings Significant proteinuria, RBC, RBC casts
    • Crystal-induced ARF Uric acid (tumor-lysis) Oxalate (ethylene glycol) Methotrexate Acyclovir Sulfonamides Oxalate Indinavir Phospho Soda Uric Acid
    • Indinavir- Urine Crystals Gagnon RF.. Am J Kidney Dis 2000 Sep;36(3):507-515
    • Osmotic Nephrosis Sucrose Mannitol Intravenous immunoglobulin Radiocontrast agents Dextran Hydroxyethyl starch Ebcioglu Z.. Kidney International (2006) 70, 1873–1876.
    • J Am Soc Nephrol. 2005 Nov;16(11):3389-96.
    • Etiology of ATN Ischemic All pre-renal causes Endogenous Exogenous Toxins Toxins Antibiotics Hemoglobin Contrast Myoglobin Chemotherapy Light chains Org. solvents, Heavy metals
    • Radiocontrast Nephropathy Clinical Course: Onset of oliguria within 24 hours Peak creatinine in 4-5 days followed by recovery in the majority Differential diagnosis: atheroembolic disease Risk factors: Age Chronic kidney disease esp. diabetes Pre-renal azotemia (e.g. cirrhosis, CHF) Volume of contrast
    • Contrast Nephropathy Risk S Creatinine> 0.5 mg/dl or > 25%at 48-72 h Mehran R.. J Am Coll Cardiol. 2004 Oct 6;44(7):1393-9.
    • Heme Pigment Induced ATN Rhabdomyolysis: traumatic or non-traumatic Intravascular hemolysis Mechanism uncertain: Vasoconstriction, precipitation/obstruction, toxicity of other breakdown products Concomitant volume depletion
    • Aminoglycoside Nephrotoxicity Non-oliguric renal failure Onset several days after treatment Recovery is usually complete within 3 weeks Mingeot-Leclercq MP… Antimicrob Agents Chemother. 1999 May;43(5):1003-12.
    • Top 5 Causes of ARF Am J Kidney Dis. 2002 May;39(5):930-6
    • Urinary Indices in Oliguric ARF Urinary Index Pre-renal ATN Osmolality >500 <400 (mOsom/kg) Sodium (meq/L) <20 >40 Fractional ex of Na <1 % >2% *UNa / PNa ÷ UCr / PCr
    • Urine Microscopy Red Cell Cast WBC Cast Muddy (granular) Cast Broad Cast
    • Workup of Renal Failure RENAL FAILURE Acute or Chronic Post-Renal Renal Pre-Renal Glomerular Vascular Interstitial Tubular History, Physical, Urine analysis, USG
    • Treatment of ATN-2005 SUPPORTIVE CARE • Acid-base/electrolyte balance • Fluid balance • Nutrition • Review of drugs • Dialysis: • PD, HD, Continuous modalities
    • Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury. 35 ml/kg/h 20 ml/kg/h N Engl J Med. 2008 May 20. [Epub ahead of print]
    • Course and Outcome of ATN Am J Kidney Dis. 2002 May;39(5):930-6
    • Pathogenesis of ATN Bruce A. Molitoris & Robert Bacallao
    • Tubuloglomerular feedback Endothelin Adenosine Nitric Oxide Prostacyclin
    • Pathogenesis of ATN: Reactive Oxygen Species Source of ROS: Xanthine Dehydrogenase NADH Oxidase
    • QUESTION: What preventive strategies have been consistently shown to be effective against ATN? Maintaining euvolemia ? N-acetyl cysteine ? Dopamine ? Iso-osmolar contrast ?
    • Preventive Strategies POSITIVE: Hydration EQUIVOCAL: Bicarbonate N-Acetyl Cysteine Theophylline Isoosmolar Contrast CRRT/Dialysis NEGATIVE: Atrial natriuretic peptide Anti-endothelin antagonist Fenoldopam
    • The Data Effect on Mortality Friedrich JO; Adhikari N; Herridge MS; Beyene J. Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death. Ann Intern Med 2005 Apr 5;142(7):510-24. Effect on need for Renal Replacement Therapy
    • High-dose Furosemide for Established ARF 338 pts with ARF on dialysis Furosemide (25mg/kg IV or 35mg/kg PO, or matched placebo) daily. No difference in : Survival Renal recovery Shorter time to 2L/day diuresis Am J Kidney Dis. 2004 Sep;44(3):402-9
    • Course and Outcome of ATN Am J Kidney Dis. 2002 May;39(5):930-6
    • ARF Outcomes after Discharge: Survival 979 pts who received CRRT 69% in-hospital mortality Post discharge survival: 6M: 89% 5 Y: 50% Morgera, S. American Journal of Kidney Disease 2002; 40(2):275-279
    • ARF: Outcomes after Discharge Quality of Life 77% assessed health as “Good to excellent” 69% resumed working 57% self-sustaining Most Common Complaints: Loss of energy Difficulty with heavy housework Limited physical mobility Morgera, S. American Journal of Kidney Disease 2002; 40(2):275-279 Korkeila, M. Nephrology, Dialysis, and Transplantation 2000
    • Future Developments Biomarkers: Cell-based therapy
    • Current Status of Biomarkers Neutrophil Gelatinase-associated Lipocalcin (NGAL) Kidney Injury Molecule-1 Interleukin 18 Nickolas T.. Curr Opin Nephrol Hypertens. 2008 Mar;17(2):127-132
    • 225 200 Serum Creat Rise 175 Urine NGAL (ng/ml) 150 125 100 75 ARF 50 (n=20) 25 No ARF 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 (n=51) 2 4 6 8 12 24 36 48 60 72 84 96 108 120 Post CPB Time (hours) Urine NGAL is upregulated 15-fold within 2 hours after CPB in patients who later develop ARF Lancet. 2005Apr;365(9466):1231-8.
    • Urinary NGAL at 2 Hours Post CPB 600 Sensitivity: 100% 500 Specificity: 98% Urine NGAL (ng/ml) 2 hr post CPB 400 PPV: 95% NPV: 100% 300 200 100 50 0 0 1 2 ARF No ARF (n=20) (n=51) The 2-hour urine NGAL was 50 ng/ml or higher in all patients who subsequently developed ARF Lancet. 2005Apr;365(9466):1231-8.
    • Ann Intern Med. 2008 Jun 3;148(11):810-9.
    • Conclusions ARF is common in hospitalized patients & has a high mortality A significant number of patients recover The best (and least expensive) preventive strategy is to maintain euvolumia