Acute Kidney Injury



  • An abrupt loss of kidney function, acute kidney injury (AKI) defined as (1):
    • Increase in serum creatinine (SCr) of ≥0.3 mg/dL within 48 hours
    • ≥50% increase in baseline SCr within 7 days
    • Urine output of <0.5 mL/kg/hr for 6 hours
  • Staging is based on SCr or urine output:
    StageIncrease in Baseline CreatinineIncrease in CreatinineUrine Output
    11.5 times≥0.3 mg/dL<0.5 mL/kg/hr for 6–12 hours
    22.0–2.9 timesN/A<0.5 mL/kg/hr for ≥12 hours
    33.0 times≥4.0 mg/dL<0.3 mL/kg/hr for ≥24 hours

  • The result is retention of nitrogenous waste, electrolyte, acid–base, and volume abnormalities (1).



  • 5% of hospital and 30% of ICU admissions have AKI. 25% of patients develop AKI while hospitalized; 50% of these cases are iatrogenic.
  • Developing AKI as an inpatient is associated with >4-fold increased risk of death (2).

Etiology and Pathophysiology

Three categories: prerenal, intrarenal, and postrenal

  • Prerenal (reduced renal perfusion, typically reversible):
    • Decreased renal perfusion (often due to hypovolemia) leads to a decrease in glomerular filtration rate (GFR)
    • Caused by hypotension, volume depletion (GI losses, excessive sweating, diuretics, hemorrhage); renal artery stenosis/embolism; burns; heart/liver failure; if decreased perfusion is prolonged or severe, can progress to ischemic acute tubular necrosis (ATN)
  • Intrarenal (intrinsic kidney injury, often from prolonged or severe renal hypoperfusion)
    • ATN—from prolonged prerenal azotemia, radiographic contrast material, aminoglycosides, nonsteroidal anti-inflammatory drugs (NSAIDs), or other nephrotoxic substances
    • Glomerulonephritis (GN)
    • Acute interstitial nephritis (AIN; drug induced), arteriolar insults, vasculitis, accelerated hypertension, cholesterol embolization (following an intra-arterial procedure), intrarenal deposition/sludging (uric acid nephropathy and multiple myeloma [Bence Jones proteins])
  • Postrenal (obstruction of the collecting system)
    • Extrinsic compression (e.g., benign prostatic hypertrophy [BPH], carcinoma, pregnancy); intrinsic obstruction (e.g., calculus, tumor, clot, stricture, sloughed papillae); decreased function (e.g., neurogenic bladder), leading to obstruction of the urinary collection system

No known genetic pattern

Risk Factors

  • Chronic kidney disease (CKD); comorbid conditions (e.g., diabetes mellitus, hypertension, heart failure, liver failure); advanced age; radiocontrast material exposure (intravascular), female gender, African American
  • Medications that impair autoregulation of GFR (NSAIDs, angiotensin-converting enzyme inhibitors [ACEIs], angiotensin II receptor blockers [ARBs], cyclosporine/tacrolimus)
  • Nephrotoxic medications (e.g., aminoglycoside antibiotics, platinum-based chemotherapy); hypovolemia (e.g., diuretics, hemorrhage, GI losses); sepsis, surgery, rhabdomyolysis, burns; solitary kidney (risk in nephrolithiasis); BPH; malignancy (e.g., multiple myeloma)

General Prevention

  • Maintain adequate renal perfusion with isotonic fluids, vasopressor support if necessary.
  • Avoid nephrotoxic agents.

Commonly Associated Conditions

Hyperkalemia, hyperphosphatemia, hypercalcemia, hyperuricemia, hydronephrosis, BPH, nephrolithiasis, congestive heart failure (CHF), uremic pericarditis, cirrhosis, CKD, malignant hypertension, vasculitis, drug reactions, sepsis, severe trauma, burns, transfusion reactions, recent chemotherapy, rhabdomyolysis, internal bleeding, dehydration


AKI is usually asymptomatic until the patient has experienced severe loss of function. Oliguria can be present, but it is neither specific nor sensitive.


  • Thorough medication history; changes in oral intake, urine output, and body weight
  • Prerenal: thirst, orthostatic symptoms, vomiting, diarrhea, bleeding
  • Intrarenal: nephrotoxic medications, radiocontrast material, other toxins
  • Postrenal: colicky flank pain that radiates to the groin suggests ureteric obstruction such as a stone; nocturia, frequency, and hesitancy suggest prostatic disease; suprapubic and flank pain are usually secondary to distension of the bladder and collecting system; anticholinergic drugs inhibit bladder emptying.
  • Uremic symptoms: lethargy, altered mental status, nausea, vomiting, anorexia, metallic taste

Physical Exam

  • Uremic signs: altered mental status, seizures, myoclonus, pericardial friction rub, peripheral neuropathies
  • Prerenal signs: tachycardia, decreased jugular venous pressure (JVP), orthostatic hypotension, dry mucous membranes, decreased skin turgor; comorbid stigmata of sepsis, liver disease, or heart failure
  • Intrinsic renal signs: pruritic rash, livedo reticularis, subcutaneous nodules, ischemic digits despite good pulses
  • Postrenal signs: suprapubic distension, flank pain, enlarged prostate

Diagnostic Tests & Interpretation

Initial Tests (lab, imaging)

  • Compare to baseline renal function (creatinine [Cr] and GFR) (1)[A]
  • Urinalysis: dipstick for blood and protein; microscopy for cells, casts, and crystals (1)[A]
  • Sterile pyuria (especially WBC casts) suggests AIN; triad of fever, rash, and eosinophilia present in 10% of cases
  • Proteinuria, hematuria, and edema, often with nephritic urine sediment (RBCs and RBC casts), suggest GN or vasculitis.
  • Casts: transparent hyaline casts—prerenal etiology; pigmented granular/muddy brown casts—ATN; WBC casts—AIN; RBC casts—GN
  • Urine eosinophils: ≥1% eosinophils suggest AIN (poor sensitivity)
  • Urine electrolytes in an oliguric state
    • FENa = [(urinary Na × serum Cr)/(serum Na × urinary Cr)]
    • FENa <1% suggests prerenal etiology and >2% indicates intrinsic cause
    • If on diuretics, use FEurea instead of FENa. FEurea (percent) = [(serum Cr × urine urea)/(serum urea × urinary Cr] × 100; FEurea <35% suggests prerenal etiology and >50% suggests intrinsic disease
  • CBC, BUN, serum Cr, electrolytes (including Ca/Mg/P); consider arterial or venous blood gas (ABG/VBG)
  • Common lab abnormalities in AKI
    • Increased: potassium, phosphate, magnesium, uric acid
    • Decreased: hemoglobin, calcium
  • Calculate creatinine clearance (CrCl) to ensure appropriate medication dosing
  • Imaging:
    • Renal ultrasound (US): first line; excludes postrenal causes; identifies kidney size, nephrolithiasis
    • Doppler-flow renal US: evaluates for renal artery stenosis/thrombosis
    • Abdominal x-ray (kidney, ureter, bladder [KUB]): identifies calcification, renal calculi, kidney size
  • Novel biomarkers such as urinary IL-18, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), plasma cystatin C, TIMP-2, and IGFBP7 under investigation (3)

Follow-Up Tests & Special Considerations

  • Consider CK (rhabdomyolysis) and immunologic testing (if GN or vasculitis suspected).
  • Advanced imaging if initial tests unrevealing
    • Prerenal: US as effective as CT for obstruction; noncontrast helical CT: most sensitive test for nephrolithiasis
    • Radionuclide renal scan: evaluates renal perfusion, function (GFR), and presence of obstructive uropathy and extravasation. MRI: acute tubulointerstitial nephritis with increased T2-weighted signal.
    • Avoid gadolinium contrast in at-risk patients (those with diabetes mellitus and GFR <45 mL/min/1.73 m2, or those without diabetes and GFR <30 mL/min/1.73 m2). If necessary, use intravenous fluids before and after contrast administration.

Diagnostic Procedures/Other
Cystoscopy with retrograde pyelogram evaluates for bladder tumor, hydronephrosis, obstruction, and upper tract abnormalities without risk of contrast nephropathy.

Test Interpretation
Kidney biopsy: last resort if patient does not respond to therapy or if diagnosis remains unclear; most useful to evaluate intrinsic AKI of unclear cause (AIN, GN, vasculitis, or renal transplant rejection)


Fluid resuscitation is the mainstay of treatment of AKI, both in prerenal and in some forms of intrinsic kidney injury. In severe cases of kidney injury, renal replacement therapy (RRT) may be required. The most important aspect of treating AKI is determining the underlying cause.

General Measures

  • Identify and correct prerenal and postrenal causes; stop nephrotoxic drugs and renally dose others. Strictly monitor intake/output and daily weight; optimize cardiac output to maintain renal perfusion. Optimize nutrition and treat any infections. Remove obstruction by placing a Foley catheter, suprapubic catheter, or nephrostomy tube as clinically indicated.
  • Indications for RRT: volume overload, severe hyperkalemia, or metabolic acidosis refractory to medical management; advanced uremic complications (pericarditis, encephalopathy, bleeding diathesis); pulmonary edema


First Line

  • Find and treat the underlying cause. Correct electrolyte imbalances—particularly hyperkalemia.
    • If patient is oliguric and not volume overloaded, a monitored fluid challenge may help.
  • Furosemide is ineffective in preventing and treating AKI but can (judiciously) be used to manage volume overload and/or hyperkalemia. Furosemide stress test may predict the likelihood of progressive AKI, need for RRT, and mortality.
  • Fenoldopam, a dopamine agonist, has been equivocal in decreasing risk of RRT and mortality in AKI; not currently recommended (1)[C].
  • Hyperkalemia with ECG changes: Give IV calcium gluconate, isotonic sodium bicarbonate (only if acidemic, and avoid use of hypertonic “amps” of NaHCO3), glucose with insulin, and/or high-dose nebulized albuterol (to drive K+ into cells); Kayexalate and/or furosemide (to increase K+ excretion); hemodialysis if severe/refractory.
  • Fluid restriction may be required for oliguric patients to prevent worsening hyponatremia.
  • Effective strategies for AKI prevention: isotonic IVF, once-daily dosing of aminoglycosides; use of lipid formulations of amphotericin B, use of iso-osmolar nonionic contrast media.
  • Risk of contrast-induced AKI is reduced by avoidance of hypovolemia:
    • Inpatients: Isotonic saline 1 mL/kg/hr 6–12 hours preprocedure, during the procedure and 6–12 hours postprocedure.
    • Outpatients: Isotonic saline 3 mL/kg/hr × 1 hour preprocedure, 1 to 1.5 mL/kg/hour × 4–6 hours during and after the procedure for a total of 6 ml/kg

Second Line

  • Tamsulosin or other selective α-blockers for bladder outlet obstruction secondary to BPH.
  • Dihydropyridine calcium channel blockers may have a protective effect in posttransplant ATN.

Issues For Referral

  • Consider nephrology consultation for potential initiation of RRT; persistent and prolonged anuria or oliguria and/or refractory elevation in BUN and/or Cr despite appropriate fluid and/or electrolyte replacement, and/or underlying structural or functional renal disease (e.g., glomerulonephropathies, SLE nephritis, cryoglobulinemia), and/or renal transplant patients.
  • Consider urology consult for obstructive nephropathy.

Surgery/Other Procedures

  • Relieve obstruction by retrograde ureteral catheters/percutaneous nephrostomy.
  • Hemodialysis catheter placement

Complementary and Alternative Medicine

Many herbal and dietary supplements are potentially nephrotoxic (aristolochic acid, ochratoxin A, Djenkol bean, impila [Callilepis laureola]), orellanine, cat’s claw, Chinese yew (Taxus celebica), morning cypress (Cupressus funebris [Endl]), St. John’s wort.

Admission, Inpatient, and Nursing Considerations

  • Treat life-threatening complications: hyperkalemia, metabolic acidosis, volume overload, and advanced uremia
  • Monitor strict intake and output through fluid balance and daily weights.
  • Consider urinary catheter placement to quantify urine output, weighing risks of catheter-associated urinary tract infection (CAUTI). Remove as soon as possible. Stabilize renal function and ensure treatment plan prior to discharge; dialysis if necessary.

Ongoing Care

Follow-up Recommendations

Nephrology follow-up if persistent renal impairment and/or proteinuria


  • Total caloric intake of 20 to 30 kcal/kg/day (1)
  • Restrict Na+ to 2 g/day (unless hypovolemic); consider K+ restriction (2 to 3 g/day) if hyperkalemic. If hyperphosphatemic, consider use of phosphate binders, although no evidence of benefit in AKI. Avoid magnesium- and aluminum-containing compounds.

Patient Education


  • In cases of prerenal and postrenal AKI, short duration of AKI correlates with good rates of recovery.
  • Among patients who require RRT for AKI, recovery more likely with higher baseline GFR, AKI from ATN due to sepsis or surgery; recovery less likely with preexisting heart failure.


Death, sepsis, infection, CKD, seizures, paralysis, peripheral edema, CHF, arrhythmias, uremic pericarditis, bleeding, hypotension, anemia, hyperkalemia, uremia

Additional Reading

See Also

Algorithm: Anuria or Oliguria



  • N17 Acute kidney failure
  • N17.0 Acute kidney failure with tubular necrosis
  • N17.1 Acute kidney failure with acute cortical necrosis
  • N17.2 Acute kidney failure with medullary necrosis
  • N17.8 Other acute kidney failure
  • N17.9 Acute kidney failure, unspecified


  • 140031000119103 Acute nontraumatic kidney injury
  • 14669001 Acute renal failure syndrome
  • 236428007 Nephrotoxic acute renal failure
  • 236429004 Acute drug-induced renal failure
  • 430535006 Acute renal failure with oliguria
  • 58574008 Acute nephropathy

Clinical Pearls

  • Three categories of AKI:
    • Prerenal: decreased renal perfusion (often from hypovolemia) leading to a decrease in GFR; reversible
    • Intrarenal: intrinsic kidney damage; ATN most common due to ischemic/nephrotoxic injury
    • Postrenal: extrinsic/intrinsic obstruction of the urinary collection system
  • Indications for emergent hemodialysis: severe hyperkalemia, metabolic acidosis, or volume overload refractory to conservative therapy; uremic pericarditis, encephalopathy, or neuropathy; and selected alcohol and drug intoxications
  • Management of ATN is supportive; no specific treatments are proven to effectively hasten recovery.
  • Fluid management remains a mainstay of treatment in prerenal and intrinsic kidney injury.


Michelle Nelson, MD
Arturas Klugas, MD, FAAFP


  1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Inter. 2012;(Suppl 2):1–138.
  2. Gonsalez SR, Cortês AL, Costa da Silva R, et al. Acute kidney injury overview: from basic findings to new prevention and therapy strategies. Pharmacol Ther. 2019;200:1–12. [PMID:30959059]
  3. Gameriero J, Fonseca JA, Outerelo C, et al. Acute kidney injury: from diagnosis to prevention and treatment strategies. J Clin Med. 2020;9(6):1704. [PMID:32498340]

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