Acute Renal Failure: Only three possible causes: 1. Inadequate perfusion 2. Intrinsic renal damage 3. Obstruction to the outflow of urine

Is Renal Failure Acute or Chronic? History: Get the old records Take a history: –Longstanding or progressive symptoms? –Underlying illnesses? –Medications, including OTC meds? –Prior MD encounters or laboratory work? Physical examination: –Does the patient appear chronically ill? –Volume status? –Diabetic retinopathy? Ultrasound Laboratory data: –Anemia –Creatinine level?

Acute Renal Failure: Always rule out obstruction. Pre-renal vs. intrinsic damage. –Urine sodium, FENa –Urine sediment Caveats: –Contrast nephropathy –Pigment nephropathy –Heart failure –Liver failure

Genesis of Acute Tubular Necrosis Tubular obstruction by debris Backleak across damaged epithelium Proximal tubular damage leading to increased delivery to the macular densa with consequent reduction in GFR mediated by GT feedback.

Acute Renal Failure: Most Common Causes at PHD Sepsis Post-surgical (AAA, CABG ) Rhabdomyolysis Drugs: –Contrast –NSAIDs –Illicit/suicidal –All of the above

Acute Tubular Necrosis: Reversing the Process or Speeding Recovery? Diuretics Atrial natriuretic peptide Low dose dopamine Fenoldapam Volume

Anaritide in acute tubular necrosis. Auriculin Anaritide Acute Renal Failure Study Group The administration of anaritide did not improve the overall rate of dialysis-free survival in critically ill patients with acute tubular necrosis. However, anaritide may improve dialysis-free survival in patients with oliguria and may worsen it in patients without oliguria who have acute tubular necrosis. (Allgren RL; Marbury TC; Rahman SN; Weisberg LS; Fenves AZ; Lafayette RA; Sweet RM; Genter FC; Kurnik BR; Conger JD; Sayegh MH: N Engl J Med 1997 Mar 20;336(12):828-34)

Low-dose dopamine in patients with early renal dysfunction: a placebo- controlled randomised trial. Australian and New Zealand Intensive Care Socity (ANZICS) Clinical Trials Group Administration of low-dose dopamine by continuous intravenous infusion to critically ill patients at risk of renal failure does not confer clinically significant protection from renal dysfunction. (Bellomo R; Chapman M; Finfer S; Hickling K; Myburgh J; Lancet 2000 Dec 23-30;356(9248): )

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure. rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity. (Hirschberg R; Kopple J; Lipsett P; Benjamin E; Minei J; Albertson T; Munger M; Metzler M; Zaloga G: Murray M; Lowry S; Conger J; McKeown W; O’shea M; Baughman R; Wood K; Haupt M; Kaiser R; Simms H; Warnock D; Summer W; Hintz R; Myers B; Haenftling K; Capra W; et al; Kidney Int 1999 Jun; 55(6): )

Acute Tubular Necrosis: Reversing the Process or Speeding Recovery: Once the insult has occurred, no pharmacologic intervention has been demonstrated to be of any benefit.

Acute Tubular Necrosis: Treatment Optimize volume –Physical examination –Chest xray –Hemodynamic measurements? Stop potential nephrotoxins; avoid repeated insults –Dye studies –Surgery –NSAIDs

Question: Acute renal failure occurs on day 1 with a creatinine of 1.2. On day 3, creatinine is 3.2. On day 6, creatinine is 7.0 Renal function is: –getting better? –unchanged? –getting worse?

Question: Acute renal failure occurs on day one when a patient’s sole remaining kidney is removed for malignancy. Creatinine is 1.2. On day 3, creatinine is 3.2. On day 7, creatinine is 7.0. Renal function is: –getting better? –staying the same? –getting worse?

Acute Tubular Necrosis: Treatment Check the MAR daily for inappropriate drugs or wrong dosages. Do not depend on pharmacy alerts. Avoid hypotension and overzealous short-term blood pressure management. Watch potassium. Meticulous general medical care. –nursing –line changes Nutritional support? –Enteral if feasible –Little evidence supporting benefit of TPN in an illness of less than two weeks –If nutritional therapy is initiated, 1.5 gm/kg of protein

Acute Tubular Necrosis: Dialysis When? –Volume status and electrolytes –Etiology and anticipated course –urine output –Risk Biocompatible membranes Hemodialysis vs. CVVHD Is more better?

Acute Tubular Necrosis: Outcome ICU mortality = 50%

Acute Tubular Necrosis: Prevention Adequate volume status prior to an anticipated insult. Drugs: –NSAIDs –IV contrast »minimize dosage »avoid multiple sequential doses »avoid concomitant or recent NSAIDs »Newer agents »mucomyst »fenoldapam Delay surgical procedures after a possible insult. Avoid the second hit.

Acute Tubular Necrosis: ref: Diagnosis and Treatment of Acute Tubular Necrosis. Essen ML, and Schrier RW, Annals of Internal Medicine 137:744, 5Nov02.