acute renal failure (ARF)

Introduction

An abrupt decline in renal function (elevation of serum creatinine or decrease in urine output) that occurs over hours to days.

Classification

• oliguric: urine volume < 400 mL/24 hours
• nonoliguric: urine volume > 400 mL/24 hours

Etiology

• prerenal (70% of community-, 40% of hospital-acquired ARF)
  • volume depletion
    • GI losses
      • diarrhea
      • vomiting
    • blood loss, hemorrhage
    • renal loss
    • inadequate fluid intake
    • insensible losses
      • burns
      • sweating
  • diminished effective blood volume
    • hypotension
      • sepsis
      • excessive response to antihypertensive agent
        • in older adults with unplanned hospitalizations, frailty or polypharmacy, starting antihypertensive treatment is linked to acute kidney injury & risk of falls
      • anaphylaxis
      • anesthesia
    • heart failure
    • acute coronary syndrome
    • massive pulmonary embolism
  • vasospasm, intrarenal vasoconstriction
    • ischemia
    • drugs: NSAIDs, COX-2 inhibitors calcineurin inhibitors (cyclosporine), amphotericin B, contrast agents
    • malignant hypertension
    • pre-eclampsia
    • hypercalcemia
    • hepatorenal syndrome
  • efferent arteriolar vasodilation
    • ACE inhibitors, ARB
    • renin inhibitors
  • bilateral renal artery occlusion
  • abdominal compartment syndrome
  • common mechanism is ischemia
  • elderly are especially susceptible to pre-renal azotemia
    • predisposition to hypovolemia
    • prevalence of renal artery atherosclerosis
• intrinsic renal failure
  • acute tubular necrosis (85%)
    • prolonged ischemia (50%) - sustained pre-renal azotemia
    • nephrotoxic agents (35%)
      • heavy metals
      • aminoglycosides
      • radiographic contrast media
        • ARF within 24 hr with rapid resolution
        • especially hazardous in diabetics with serum creatinine > 2 mg/dL
      • amphotericin B
      • myoglobin, rhabdomyolysis
      • hemoglobin (intravascular hemolysis)
    • combined factors involving nephrotoxins
      • aminoglycoside & sepsis
      • radiocontrast agent & ACE inhibitor
      • NSAID & congestive heart failure (CHF)
  • arteriolar injury
    • accelerated hypertension
    • vasculitis
      • polyarteritis nodosa
    • microangiopathic
      • TTP/HUS
      • preeclampsia
      • HELLP syndrome
      • sickle cell disease
      • scleroderma renal crisis
      • hypertensive crisis
      • snake bite
    • hypercalcemia
    • scleroderma
  • glomerulonephropathies (5%) rapidly progressive glomerulonephritis
    • ANCA-associated vasculitis
    • anti-glomerular basement membrane disease
    • immune complex glomerulonephritis
      • lupus nephritis
      • endocarditis
      • post-infectious glomerulonephritis
      • cryoglobulinemia
      • IgA nephropathy
      • Henoch-Schonlein purpura
  • acute interstitial nephritis (AIN) (10%)
    • allergic reaction to drug (most common)
    • autoimmune disease (SLE)
      • lupus nephritis, Sjogren syndrome, IgG4 disease
    • sarcoidosis
    • infectious agents (pyelonephritis)
      • Legionella
      • Hantavirus
      • Leptospirosis
    • lymphoma, leukemia, myeloma
  • intrarenal (tubular) deposition/precipitation
    • uric acid in tumor lysis syndrome
    • immunoglobulin in myeloma
    • drugs: sulfonamides, triamterene, ciprofloxacin, acyclovir, indinavir, methotrexate, orlistat, vitamin C (large doses), sodium phosphate
    • toxins: ethylene glycol (calcium oxalate)
  • atheroembolic renal failure (cholesterol embolization)
    • post arterial procedure, i.e. left heart catheterization
    • ARF after 24 hr (slower onset than ARF due to radiographic contrast media)
    • other evidence of cholesterol emboli
    • poor prognosis for recovery of renal function
  • atherosclerosis
    • renal artery atherosclerotic plaque
    • dissecting aneurysm affecting renal artery
  • renal allograft rejection
  • renal cortical necrosis (complete anuria)
• postrenal (obstructive uropathy)
  • obstruction in the renal pelvis
  • ureteral obstruction
    • blood clot
    • calculus - oxalate
    • sloughed papillae (papillary necrosis)
    • external compression
      • tumor (colon)
      • retroperitoneal fibrosis
      • radiation
  • bladder outlet obstruction (98% of males)
    • neurogenic bladder
    • prostatic hypertrophy
    • carcinoma (prostate cancer, cervical, bladder cancer)
    • calculus
    • blood clot
    • urethral stricture
  • bilateral renal vein occlusion (renal vein thrombosis)
    • membranous nephropathy most common cause
• risk factors
  • chronic renal failure
  • proteinuria
    • diabetic nephropathy
  • heart failure
  • liver disease
  • hypovolemia
  • age > 50 years
  • medications, especially NSAIDs, ACE inhibitors, ARBs, diuretics
  • surgery

Epidemiology

• incidence of acute renal failure requiring dialysis is higher than that of end-stage renal disease
• incidence higher with older age, among men, & among blacks
• 39,000 deaths/year from acute renal failure in U.S. (2009)
• 5-7% of hospital admissions, up to 30% of ICU admissions
• common among critically ill children & young adults & is associated with poor outcomes, including increased mortality
• hospitalization for acute kidney injury increased in U.S. from 2000-2014 from 23 to 55 per 1000 persons
  • among patients without diabetes, from 4 to 12 per 1000
• prerenal azotemia is the most common form of acute renal failure in outpatients
  • prolonged prerenal azotemia may lead to acute tubular necrosis
• the most common cause of hospital acquired acute kidney injury is acute tubular necrosis
  • acquired acute tubular necrosis is most commonly caused by toxins, in particular nephrotoxic antibiotics such as aminoglycosides
• obstruction of the ureters or renal pelvis must be bilateral to cause acute kidney injury

Pathology

• kidney function generally normal with prerenal azotemia
• intrinsic renal disease
  • complete or partial impairment of renal function resulting in an increase of serum creatinine of 0.5-2.0 mg/dL/day
  • with complete renal failure, serum creatinine increases 1-2 mg/dL/day
  • an increase of serum creatinine of 1 mg/dL/day indicates a creatinine clearance of < 10 mL/min

History

• nephrotoxic agents (see etiology)

Clinical manifestations

• generally non-specific
  • may be asymptomatic until advanced disease
• dependent upon rapidity of onset
  • acute tubular necrosis from aminoglycoside toxicity 5-7 days
  • drug-induced acute interstitial nephritis 7-10 days
  • contrast nephropathy 24-48 hours, serum creatinine peak at 3 days
  • infection-related glomerulonephritis 1-6 weeks
• symptoms of uremia
• gastrointestinal:
  • anorexia
  • nausea/vomiting
  • diarrhea/constipation
  • metallic taste
• cardiovascular: symptoms of volume overload
  • shortness of breath
  • dyspnea on exertion
  • edema: lower extremity, periorbital
• hematologic:
  • symptoms of anemia
  • symptoms of thrombocytopenia
• genitourinary:
  • oliguria or anuria
    • urine volume < 0.5 mL/kg/hour for 6 hours
  • costovertebral angle (CVA) tenderness
  • hematuria
  • foamy urine

Diagnostic criteria

• an increase in serum creatinine of >= 0.3 mg/dL within 48 hours
• an increase in serum creatinine of >= 1.5 time baseline over 7 days
• a urine volume of < 0.5 mL/kg/hr for 6 hours

Laboratory

• serum chemistries
  • serum creatinine
    • increase of >= 0.3 mg/dL within 48 hours or
    • >= 1.5 X baseline within 7 days
  • serum urea nitrogen (BUN)
  • BUN/creatinine ratio
    • prerenal: > 20/1
    • acute tubular necrosis: 10/1
    • acute interstitial neprhitis, glomerulonephritis, vascular injury, intrarenal obstruction: variable
    • postrenal: > 20/1
  • serum potassium
  • serum bicarbonate
  • serum transaminases
  • serum creatine kinase
• complete blood count (CBC)
  • white blood cell count (WBC)
  • hematocrit
  • platelet count
• peripheral blood smear:
  • schistocytes, evidence of hemolysis (TTP/HUS)
• urinalysis
  • specific gravity:
    • > 1.020 prerenal azotemia
    • < 1.012 intrinsic renal failure
  • red blood cells (RBC): AIN, glomerulonephritis
    • dysmorphic erythrocytes (glomerulonephritis)
  • white blood cells (WBC)
    • urine eosinophils (AIN, cholesterol emboli)
    • pyuria (pyelonephritis, AIN)
    • leukocyte casts (AIN)
  • urine protein
  • urine volume of < 0.5 mL/kg/hr for 6 hours
  • RBC casts: intrinsic renal failure, glomerulonephritis
  • hyaline casts (prerenal azotemia)
  • muddy brown, broad casts or tubular epithelial cells (ATN)
• urine chemistries
  • fractional excretion of sodium (FENA)
    • < 1% prerenal & glomerulonephritis
    • > 1% renal or post renal (obstructive uropathy)
      • FENA may be low in early obstructive uropathy but may be high in late obstructive uropathy (ATN), thus is not helpful
    • > 2% ATN
    • FENA may be increased in patients taking diuretics
      • calculate fractional excretion of urea
  • urine sodium:
    • < 20 meq/L prerenal
    • > 40 meq/L renal (ATN, AIN)
    • < 40 meq/L acute glomerulonephritis
    • postrenal: variable
  • urine osmolality:
    • > 500 mosm/kg prerenal azotemia
    • < 250-300 msom/kg intrinsic renal failure
    • postrenal: variable
  • urine/serum creatinine ratio
    • > 40 prerenal azotemia
    • < 20 intrinsic renal failure
  • fractional excretion of urea < 35% consistent with diuretic-associated prerenal acute kidney injury
  • renal failure index
• urine myoglobin of questionable utility
• serologies
  • CH50 for complement deficiency
  • antinuclear antibody (ANA)
  • antistreptolysin O (ASO) titer
  • antiglomerular basement membrane (anti GBM) titer
  • anti-neutrophil cytoplasmic antibody (ANCA)
• serum protein electrophoresis
• urine protein electrophoresis - Bence-Jones proteins
• 24 hour urine
  • creatinine clearance
  • 24-hour urine protein: nephrotic syndrome
  • oliguria, anuria
• renal biopsy
  • diagnosis remains unclear
  • pre-renal & post-renal etiologies excluded

Radiology

• ultrasound
  • renal ultrasound (kidneys, ureters, bladder) is preferred imaging modality
    • diagnostic procedure of choice in obstructive uropathy
      • oliguria, normal urine (priority over FENA)
    • kidney size, solitary kidney
      • large kidney: amyloidosis, early diabetes, HIV nephropathy
      • small kidney
    • hydronephrosis
      • may not show hydronephrosis within 24 hours of onset or with retroperitoneal fibrosis
    • evidence of obstructive uropathy
      • nephrolithiasis
      • BPH with urinary obstruction
      • urinary neoplasm
      • retroperitoneal fibrosis
  • pelvic ultrasound
• pyelogram - gold standard, but seldom utilized
• renal flow scan Complication:
  • acute renal failure requiring hemodialysis is a cardiovascular risk factor
  • acute renal failure does not independently predict progession to chronic renal failure
  • acute renal failure demonstrated by rising serum creatinine may be associated with diminished clearance of renally cleared drugs
    • elevated gabapentin levels due to diminished clearance may manifest as dizziness

Differential diagnosis

• minimal proteinuria, no hematuria or pyuria, muddy brown casts
  • acute tubular necrosis
• erythrocytes, eruythrocyte casts, dysmorphic erythrocytes in urine
  • glomerulonephritis
• pyruria: pyelonephritis or acute interstitial nephritis
• eosinophilia, eosinophiluria, rash
  • acute interstitial nephritis or cholesterol emboli
• livedo reticularis: cholesterol emboli or vasculitis
• hypercalcemia & anemia: multiple myeloma
• nephrotic syndrome: diabetes mellitus, renal vein thrombosis
• obstructive uropathy on ultrasound
  • benign prostatic hypertrophy, nephrolithiasis, retroperitoneal fibrosis malignancy
• anuria: renal cortical necrosis
• large kidneys on ultrasound
  • amyloidosis, early diabetes mellitus, HIV1 nephropathy
• renal failure following bowel preparation
  • renal calcium phosphate crystal deposition
• recent abdominal surgery, hemorrhage or acute pancreatitis
  • abdominal compartment syndrome
• schistocytes in peripheral blood, thrombocytopenia
  • microangiopathic hemolytic anemia, TTP/HUS, DIC, scleroderma renal crisis
• urine dipstick positive for blood, no erythrocytes on urine microscopy
  • hemolysis, rhabdomyolysis
• acute kidney injury associated with acute leukemia, lymphoma or treatment
  • tumor lysis syndrome
• acute renal failure with diuretic-resistant heart failure
  • cardiorenal syndrome
• acute renal failure with cirrhosis & ascites
  • hepatorenal syndrome

Management

• general
  • prerenal & postrenal causes are often rapidly reversible
  • monitor input & output - foley catheter
    • the lower the urine output, the worse the prognosis
  • identify nephrotoxic agents
• optimize intravascular volume
  • a fluid challenge is indicated in the absence of volume overload:
    • 500-1000 mL of normal saline over 30-60 min
    • increased urine flow may result in patients with:
      • prerenal azotemia
      • patients with intrinsic renal disease
    • if no response to saline bolus
      • 100 to 400 mg of IV Lasix
      • metolazone 5-10 mg PO in addition to Lasix may facilitate urine output
  • loop diuretic if volume overloaded of uncertain benefit
  • invasive monitoring of central venous pressure may be indicated
  • IV albumin (25%) for cirrhotic patients with intravascular volume depletion
  • dopamine & mannitol of no value
• optimize cardiac output
• avoid further renal insults
  • discontinue nephrotoxic agents
    • ACE inhibitors
    • diuretics
    • cyclosporine
    • NSAIDs
  • avoid contrast agents
  • dose adjustment as needed for renally-cleared pharmaceutical agents
  • hydromorphone, fentanyl, methadone, buprenorphine, hydrocodone show minimal pharmacokinetic changes in patients with renal failure
• treat hyperkalemia
• treat underlying conditions
  • sepsis - antibiotics
  • glomerulonephritis - immunosuppressive agents
  • relieve obstruction
    • foley catheter for bladder outlet obstruction
    • nephrostomy if obstruction is above the bladder
  • metabolic acidosis: IV bicarbonate or hemodialysis
  • hypertension:
    • vasodilators, beta-blockers, calcium-channel blockers
    • avoid renally-cleared antihypertensives
  • sclerodermal renal crisis
    • ACE inhibitor regardless of serum creatinine or dialysis
  • surgical decompression for abdominal compartment syndrome
  • contrast nephropathy:
    • prophylaxis with IV saline for CKD4 or acute kidney injury
    • acute kidney injury not prevented by dialysis immediately after contrast administration
    • do not use acetylcysteine or IV bicarbonate to prevent acute kidney injury
• fluid restriction if euvolemic or volume overloaded
  • 1 to 1.5 L/day
• avoid Mg+2 containing antacids
  • do not use dopamine or mannitol
• hemodialysis or renal replacement therapy
  • indications:
    • refractory hyperkalemia
    • refractory acidosis (pH < 7.20)
    • volume overload
      • pulmonary edema refractory to medical management
    • signs or symptoms of uremia
      • altered mental status
      • asterixis
      • uremic pericarditis; pericardial friction rub
      • vomiting
    • certain drug toxicities
    • prolonged acute renal failure (> a few days)
    • do not withhold dialysis until BUN & serum creatinine reach a threshold value
• early initiation of hemodialysis does not improve outcomes (mean serum creatinine 7.4 mg/dL vs 10.6 mg/dL) or (serum creatinine 3.7 mg/dL vs ESRD)
• no benefit to early hemodialysis
  • when hemodialysis is delayed, nearly 1/2 of patients never require it; those that do need hemodialysis are more likely to die
  • early hemodialysis of no benetit to patients with septic shock or ARDS
  • continuous renal replacement therapy
    • continuous venovenous hemofiltration (CVVH)
    • continuous arteriovenous hemofiltration (CAVH)
    • treatment of choice in patients who are hemodynamically unstable & unable to tolerate standard hemodialysis
• diet
  • protein restriction for control of uremia (do not restrict dietary protein in acute renal failure)
  • sodium restriction < 2 g/day
  • potassium restriction < 2 g/day
  • phosphate restriction & PhosLo (calcium acetate)
• post-acute tubular necrosis (ATN) diuresis
  • generally occurs prior to drop in creatinine
  • avoid volume depletion
• treatment of hyperuricemia generally not necessary if serum uric acid is < 15 mg/dL
• prevention:
  • fenoldopam may reduce risk of acute renal failure in critically ill patients
  • fenoldopam of no benefit for acute kidney injury* after cardiac surgery
  • neither aspirin nor clonidine given perioperatively lowers risk for acute renal failure

More general terms

• renal failure; kidney failure
• acute kidney disease

More specific terms

• acute renal failure in malignancy
• acute renal failure in pregnancy
• acute tubular necrosis; tubulorrhexis (ATN)
• cardiorenal syndrome
• hepatorenal syndrome; acute kidney injury in cirrhosis
• medication-induced acute kidney injury
• scleroderma renal crisis

Additional terms

• fractional excretion of sodium (FENA)
• immediate treatment of acute renal failure (ARF)
• nephrotoxic substances
• postrenal azotemia; obstructive uropathy
• prerenal azotemia
• renal failure index (RFI)