Acute Renal Failure Deb Goldstein Argy Resident September, 2005
Acute Renal Failure • Rapid decline in the GFR over days to weeks. • Cr increases by >0.5 mg/dL • GFR <10mL/min, or <25% of normal Acute Renal Insufficiency • Deterioration over days-wks • GFR 10-20 mL/min
Definitions Anuria: No UOP Oliguria: UOP<400-500 mL/d Azotemia: Incr Cr, BUN • May be prerenal, renal, postrenal • Does not require any clinical findings Chronic Renal Insufficiency • Deterioration over mos-yrs • GFR 10-20 mL/min, or 20-50% of normal ESRD = GFR <5% of nl
ARF: Signs and Symptoms • Hyperkalemia • Nausea/Vomiting • HTN • Pulmonary edema • Ascites • Asterixis • Encephalopathy
Causes of ARF in hospitalized pts 45% ATN • Ischemia, Nephrotoxins 21% Prerenal • CHF, volume depletion, sepsis 10% Urinary obstruction 4% Glomerulonephritis or vasculitis 2% AIN 1% Atheroemboli
ARF: Focused History • Nausea? Vomiting? Diarrhea? • Hx of heart disease, liver disease, previous renal disease, kidney stones, BPH? • Any recent illnesses? • Any edema, change in urination? • Any new medications? • Any recent radiology studies? • Rashes?
Physical Exam • Volume Status • Mucus membranes, orthostatics • Cardiovascular • JVD, rubs • Pulmonary • Decreased breath sounds • Rales • Rash (Allergic interstitial nephritis) • Large prostate • Extremities (Skin turgor, Edema)
W/U for ARF • Chem 7 • Urine • Urine electrolytes and Urine Cr to calculate FeNa • Urine eosinophils • Urine sediment: casts, cells, protein • Uosm • Kidney U/S - r/o hydronephrosis
FeNa = (urine Na x plasma Cr) (plasma Na x urine Cr) FeNa <1% 1. PRERENAL • Urine Na < 20. Functioning tubules reabsorb lots of filtered Na 2. ATN (unusual) • Postischemic dz: most of UOP comes from few normal nephrons, which handle Na appropriately • ATN + chronic prerenal dz (cirrhosis, CHF) 3. Glomerular or vascular injury • Despite glomerular or vascular injury, pt may still have well-preserved tubular function and be able to concentrate Na
More FeNa FeNa 1%-2% 1. Prerenal-sometimes 2. ATN-sometimes 3. AIN-higher FeNa due to tubular damage FeNa >2% • ATN • Damaged tubules can't reabsorb Na
Calculating FeNa after pt has gotten Lasix... • Caution with calculating FeNa if pt has gotten Loop Diuretics in past 24-48 h • Loop diuretics cause natriuresis (incr urinary Na excretion) that raises U Na-even if pt is prerenal • So if FeNa>1%, you don’t know if this is because pt is euvolemic or because Lasix increased the U Na • So helpful if FeNa still <1%, but not if FeNa >1% 1. Fractional Excretion of Lithium (endogenous) 2. Fractional Excretion of Uric Acid 3. Fractional Excretion of Urea
A 22yo male with sickle cell anemia and abdominal pain who has been vomiting nonstop for 2 days. BUN=45, Cr=2.2. A. ATN B. Glomerulo-nephritis C. Dehydration D. AIN from NSAIDs
Prerenal ARF • Hyaline casts can be seen in normal pts • NOT an abnormal finding • UA in prerenal ARF is normal • Prerenal: causes 21% of ARF in hosp. pts • Reversible • Prevent ATN with volume replacement • Fluid boluses or continuous IVF • Monitor Uop
Prerenal causes • Intravascular volume depletion • Hemorrhage • Vomiting, diarrhea • “Third spacing” • Diuretics • Reduced Cardiac output • Cardiogenic shock, CHF, tamponade, huge PE.... • Systemic vasodilation • Sepsis • Anaphylaxis, Antihypertensive drugs • Renal vasoconstriction • Hepatorenal syndrome
Intrinsic ARF • Tubular (ATN) • Interstitial (AIN) • Glomerular (Glomerulonephritis) • Vascular
You evaluate a 57yo man w/ oliguria and rapidly increasing BUN, Cr. • ATN • Acute glomerulonephritis • Acute interstitial nephritis • Nephrotic Syndrome
ATN • Muddy brown granular casts (last slide) • Renal tubular epithelial cell casts (below)
More ATN • Broad casts (form in dilated, damaged tubules)
ATN Causes 1. Hypotension • Relative low BP • May occur immediately after low BP episode or up to 7 days later! 2. Post-op Ischemia • Post-aortic clamping, post-CABG 3. Crystal precipitation 4. Myoglobinuria (Rhabdo) 5. Contrast Dye • ARF usually 1-2 days after test 6. Aminoglycosides (10-26%)
ATN—What to do • Remove any offending agent • IVF • Try Lasix if euvolemic pt is not peeing • Dialysis • Most pts return to baseline Cr in 7-21 days
Which UA is most compatible w/contrast-induced ATN? • Spec grav 1.012, 20-30 RBC, 15-20 WBC, +Eos • Spec grav 1.010, 1-3 WBC, 5-10 renal tubular cells, many granular casts, occasional renal tubular cell casts, no eos • Spec grav 1.012, 5-10 RBC, 25-50 WBC, many bact, occasional fine granular casts, no eos • Spec grav 1.020, 10-20 RBC, 2-4 WBC, 1-3 RBC casts, no eos
ATN B. Spec grav 1.010, 1-3 WBC, 5-10 renal tubular cells, many granular casts, occasional renal tubular cell casts, no eos • Dilute urine: failure to concentrate urine • No RBC casts or WBC casts in ATN • Eos classically in AIN or renal atheroemboli, but nonspecific
56yo woman with previously normal renal function now has BUN=24, Cr 1.8. Which drug is responsible? • Indinavir for her HIV • Gentamicin for her SBE • Motrin for her OA • Cyclosporin for her SLE
WBC Casts Cells in the cast have nuclei (unlike RBC casts) Pathognomonic for Acute Interstitial Nephritis
Acute Interstitial Nephritis 70% Drug hypersensitivity • 30% Antibiotics: PCNs (Methicillin), Cephalosporins, Cipro • Sulfa drugs • NSAIDs • Allopurinol... 15% Infection • Strep, Legionella, CMV, other bact/viruses 8% Idiopathic 6% Autoimmune Dz (Sarcoid, Tubulointerstitial nephritis/Uveitis)
AIN from Drugs Renal damage is NOT dose-dependent May take wks after initial exposure to drug • Up to 18 mos to get AIN from NSAIDS! But only 3-5 d to develop AIN after second exposure to drug • Fever (27%) • Serum Eosinophilia (23%) • Maculopapular rash (15%) • Bland sediment or WBCs, RBCs, non-nephrotic proteinuria • WBC Casts are pathognomonic! • Urine eosinophils on Wright’s or Hansel’s Stain • Also see urine eos in RPGN, renal atheroemboli...
AIN Management • Remove offending agent • Most patients recover full kidney function in 1 year • Poor prognostic factors • ARF > 3 weeks • Advanced age at onset
You evaluate a 32yo woman with HTN, oliguria, and rapidly increasing Cr, BUN. You spin her urine: • ATN • Acute glomerulonephritis • Acute interstitial nephritis • Nephrotic Syndrome
Acute Glomerulonephritis • RBC casts: cells have no nuclei • Casts in urine: think INTRINSIC renal dz • If she has Lupus w/recent viral prodrome, think Rapidly Progressive Glomerulonephritis • If she had a sore throat 10 days ago, think Postinfectious Proliferative Glomerulonephritis
Glomerular Dz • Hematuria (dysmorphic RBCs) • RBC casts • Lipiduria (increased glomerular permeability) • Proteinuria (may be in nephrotic range) • Fever, rash, arthralgias, pulmonary sx • Elevated ESR, low complement levels
Rapidly Progressive Glomerulonephritis Type 1: Anti-GBM dz Type 2: Immune complex • IgA nephropathy • Postinfectious glomerulonephritis • Lupus nephritis • Mixed cryoglobulinemia Type 3: Pauci-immune • Necrotizing glomerulonephritis (often ANCA-positive, assoc. w/vasculitis) Can present with viral-like prodrome • Myalgias, arthralgias, back pain, fever, malaise Kidney bx : Extensive cellular crescents with or w/o immune complexes Can develop ESRD in days to weeks. Treat w/glucocorticoids & cyclophosphamide.
Postinfectious Proliferative Glomerulonephritis • Usually after strep infxn of upper respiratory tract or skin – 8-14 day latent period • Can also occur in subacute bacterial endocarditis, visceral abscesses, osteomyelitis, bacterial sepsis • Hematuria, HTN, edema, proteinuria • Positive antistreptolysin O titer (90% upper respiratory and 50% skin) • Treatment is supportive • Screen family members with throat culture and treat with antibiotics if necessary
A 19yo woman with Breast Cancer s/p chemo in the ER has weakness, fever, rash. WBC=15.4, Hct 24, Cr 2.9, LDH 600, CK=600. UA=3+ prot, 3+blood, 20 RBC. What next test do you order? What’s her likely dx? • Nephrotic Syn • Systemic Vasculitis • Acute Glomerulonephritis • Hemolytic-Uremic Syn • Rhabdomyolysis
TTP • Order blood smear to r/o TTP • TTP associated with malignancy, chemo • TTP may mimic Glomerulonephritis on UA (RBCs, WBCs) • Thrombocytopenia, anemia not consistent with nephrotic or nephritic syndrome • Need CK in the thousands to cause ARF
Microvascular ARF • TTP/HUS • HELLP syndrome • Platelets form thrombi and deposit in kidneysGlomerular capillary occlusion or thrombosis • Plasma exchange, steroids, Vincristine, IVIG, splenectomy....
Macrovascular ARF • Aortic Aneurysm • Renal artery dissection or thrombosis • Renal vein thrombus • Atheroembolic disease • New onset or accelerated HTN? • Abdominal bruits, reduced femoral pulses? • Vascular disease? • Embolic source?
Your 68yo male inpatient with baseline Cr=1.2 had negative cardiac cath 4 days ago, now Cr=1.8 and blanching rash. • Renal Artery Stenosis • Contrast-Induced Nephropathy C. Abdominal Aortic Aneurysm D. Cholesterol Atheroemboli
Renal Atheroembolic Dz 1% of Cardiac caths: atheromatous debris scraped from the aortic wall will embolize • Retinal • Cerebral • Skin (Livedo Reticularis, Purple toes) • Renal (ARF) • Gut (Mesenteric ischemia) • Unlike in Contrast-Induced Nephropathy, Cr will NOT improve with IVF • Diagnosis of exclusion: will NOT show up on MRI or Renal U/S; WILL show up on renal bx • Tx: supportive
Post-Renal ARF • Urethral obstruction: prostate, urethral • stricture. • Bladder calculi or neoplasms. • Pelvic or retroperitoneal neoplams. • Bilateral ureteral obstruction (neoplasm, • calculi). • Retroperitoneal fibrosis.
“Doc, your pt hasn’t peed in 5 hrs....what do you want to do?” • Examine pt: Dry? Septic (vasodilated)? • Flush foley (sediment can obstruct outflow) • Check I/Os (has she been drinking?) • Give IV BOLUS (250-500cc IVF), see if pt pees in next 30-60 min • If she pees, then she was dry • If she doesn’t pee, then she’s either REALLY dry or in renal failure • Check UA, UCx, urine lytes • Consider Renal U/S if reasonable
You’re called to the ER to see... • A 35yo woman with previously normal renal function now with BUN=60, Cr=3.5. Do you call the Renal fellow to dialyze this pt? • What if her K=5.9? • What if her K=7.8?
Indications for acute dialysis AEIOU • Acidosis (metabolic) • Electrolytes (hyperkalemia) • Ingestion of drugs/Ischemia • Overload (fluid) • Uremia
You admit this pt to telemetry and aggressively hydrate her. • You recheck labs 6h later and BUN=85, Cr=4.2. Suddenly the pt starts to seize. • Now what?
Uremia—So what? • General • Fatigue, weakness • Pruritis • Mental status change • Uremic encephalopathy • Seizures • Asterixis • GI disturbance • Anorexia, early satiety, N/V, • Uremic Pericarditis • Plt dysfunction/bleeding
A pt with chronic lung disease has acute pleuritic pain and desats to 92%RA. You want to r/o PE but her Cr=1.4. Can you get a CT with IV contrast? • Send her for Stat CT with IV contrast • Send her for Stat CT without IV contrast C. Just give her heparin • Begin IV hydration • Begin pre-procedure Mannitol • Get a VQ scan instead
Contrast-Induced Nephrotoxicity • Cr increases by 25% or >0.05 post-procedure • Contrast causes renal vasoconstriction renal hypoxia • Iodine itself may be renally toxic • If Cr>1.4, use pre-procedure prophylaxis
Pre-Procedure Prophylaxis 1. IVF ( 0.9NS) 1-1.5 mg/kg/hour x12 hours prior to procedure and 6-12 hours after 2. Mucomyst (N-acetylcysteine) Free radical scavenger; prevents oxidative tissue damage 600mg po BID x 4 doses (2 before procedure, 2 after) 3. Bicarbonate (JAMA 2004) Alkalinizing urine should reduce renal medullary damage D5W with 3 amps HCO3; bolus 3.5 mL/kg 1 hour preprocedure, then 1mL/kg/hour for 6 hours postprocedure 4. Possibly helpful? Fenoldopam, Dopamine 5. Not helpful! Diuretics, Mannitol