Acute Kidney Injury
Abrupt loss of kidney function, defined as a rise in serum creatinine (SCr) of ≥0.3 mg/dL within 48 hours; a 50% increase in SCr within 7 days or urine output of <0.5 mL/kg/hr for >6 hours, resulting in retention of nitrogenous waste as well as electrolyte, acid–base, and volume homeostasis abnormalities (1)
- 5% of hospital and 30% of intensive care unit admissions have acute kidney injury (AKI). 25% of patients develop AKI while in the hospital; 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)
- Hypotension, volume depletion (gastrointestinal [GI] losses, excessive sweating, diuretics, hemorrhage); renal artery stenosis/embolism; burns; heart/liver failure
- Decreased renal perfusion (often due to hypovolemia) leads to a decrease in glomerular filtration rate (GFR), which (if 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
- Chronic kidney disease (CKD)
- Comorbid conditions (e.g., diabetes mellitus, hypertension, heart failure, liver failure)
- Advanced age
- Radiocontrast material exposure (intravascular)
- Medications that impair autoregulation of GFR (NSAIDs, angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), cyclosporine/tacrolimus)
- Nephrotoxic medications (e.g., aminoglycoside antibiotics, platinum-based chemotherapy)
- Hypovolemia (e.g., diuretics, hemorrhage, GI losses)
- Sepsis, surgery, rhabdomyolysis
- Solitary kidney (risk in nephrolithiasis)
- BPH; malignancy (e.g., multiple myeloma)
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 extreme loss of function. Oliguria can be present, but it is neither specific nor sensitive (3).
- Ascertain changes in oral intake, urine output, and body weight
- Thorough medication history
- Prerenal: thirst, orthostatic symptoms
- Intrarenal: nephrotoxic medications, radiocontrast material, other toxins
- Livedo reticularis, subcutaneous (SC) nodules, and ischemic digits despite good pulses suggest atheroembolization
- Flank pain may suggest renal artery or vein occlusion
- 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, nausea/vomiting, anorexia, pruritus, restless legs, sleep disturbance, hiccups
- Uremic signs: altered sensorium, seizures, asterixis, 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, SC nodules, ischemic digits despite good pulses
- Postrenal signs: suprapubic distension, flank pain, enlarged prostate
Diagnostic Tests & InterpretationInitial Tests (lab, imaging)
- Compare to baseline renal function (creatinine [Cr]/GFR) (1)[A]
- Urinalysis: dipstick for blood and protein; microscopy for cells, casts, and crystals (1)[A]
- Sterile pyuria (especially white blood cell [WBC] casts) suggests AIN; triad of fever, rash, and eosinophilia present in 10% of cases
- Proteinuria, hematuria, and edema, often with nephritic urine sediment (red blood cells [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 = [(UNa × PCr) / (PNa × UCr)] × 100
- FENa <1%, likely prerenal; >2%, likely intrarenal
- If patient on diuretics, use FEurea instead of FENa: FEurea = [(Uurea × PCr) / (PBUN × UCr)] × 100; FEurea <35% suggests prerenal etiology.
- Complete blood count, blood urea nitrogen (BUN), SCr, electrolytes (including Ca/Mg/P); consider arterial or venous blood gas (ABG/VBG).
- BUN/Cr ratio not reliable in distinguishing prerenal azotemia from AKI (4)[B]
- Common lab abnormalities in AKI
- Increased: potassium, phosphate, magnesium, uric acid
- Decreased: hemoglobin, sodium calcium
- Calculate creatinine clearance (CrCl) to ensure appropriate medication dosing
- Renal ultrasound (US): first line; excludes postrenal causes; identifies kidney size, hydronephrosis, and nephrolithiasis
- Doppler-flow renal US: evaluates for renal artery stenosis/thrombosis; operator dependent
- 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 (5)[C]
Follow-Up Tests & Special Considerations
- Consider creatine kinase (rhabdomyolysis) and immunologic testing (if GN or vasculitis suspected).
- Advanced imaging if initial tests unrevealing
- Prerenal: US as effective as computed tomography (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
- Magnetic resonance imaging: acute tubulointerstitial nephritis with increased T2-weighted signal. Gadolinium contrast is contraindicated if GFR <30 mL/min due to risk of nephrogenic systemic fibrosis.
Cystoscopy with retrograde pyelogram evaluates for bladder tumor, hydronephrosis, obstruction, and upper tract abnormalities without risk of contrast nephropathy.
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 intrinsic kidney injury. In severe cases of kidney injury, dialysis may be required, especially in cases where the patient is oliguric. The most important aspect of treating AKI is determining the underlying cause.
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
- Indications for renal replacement therapy (RRT): volume overload, severe or progressive hyperkalemia, or severe metabolic acidosis refractory to medical management; advanced uremic complications (pericarditis, encephalopathy, bleeding diathesis)
- Find and treat the underlying cause.
- Prevent fluid overload, and 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 (5)[B].
- Dopamine, natriuretic peptides, insulin-like growth factor, and thyroxine have no benefit in the treatment of AKI.
- 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.
- Metabolic acidosis (particularly pH <7.2): Sodium bicarbonate can be given (judiciously); be aware of volume overload, hypocalcemia, and hypokalemia.
- Effective strategies for AKI prevention: isotonic in vitro fertilization, once-daily dosing of aminoglycosides; use of lipid formulations of amphotericin B, use of iso-osmolar nonionic contrast media
- Risk of contrast-induced AKI reduced by avoidance of hypovolemia: isotonic saline 1 mL/kg/hr morning of procedure and continued until next morning or isotonic NaHCO3 3 mL/kg/hr × 1 hour before and 1 mL/kg/hr × 6 hours after contrast administration; N-acetylcysteine not of benefit
- 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.
- Urology consults for obstructive nephropathy
- 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, orellanine, cat’s claw). Obtain a thorough medication history from the patient.
Admission, Inpatient, and Nursing Considerations
- Treat life-threatening complications: hyperkalemia, metabolic acidosis, volume overload, and advanced uremia.
- If hypovolemic, give isotonic IV fluids.
- Monitor 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
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.
Keep well-hydrated. Avoid nephrotoxic drugs, such as NSAIDs and aminoglycosides.
- Depending on the cause, comorbid conditions, and age of patient, mortality ranges from 5% to 80%.
- In cases of prerenal and postrenal AKI, short duration of AKI correlates with good rates of recovery. Intrarenal etiologies take longer to recover.
- Even with complete recovery from AKI, affected patients are at higher subsequent risk of developing CKD and end-stage renal disease.
- Among patients who require RRT for AKI, recovery more likely with higher baseline epidermal growth factor receptor, AKI from ATN due to sepsis or surgery; recovery less likely with preexisting heart failure (6)
Death, sepsis, infection, seizures, paralysis, peripheral edema, CHF, arrhythmias, uremic pericarditis, bleeding, hypotension, anemia, hyperkalemia, uremia
- Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int. 2012;81(5):442–448. [PMID:22113526]
- McCullough PA, Kellum JA, Haase M, et al. Pathophysiology of the cardiorenal syndromes: executive summary from the eleventh consensus conference of the Acute Dialysis Quality Initiative (ADQI). Contrib Nephrol. 2013;182:82–98. [PMID:23689657]
- Singh NP, Prakash A. Nephrotoxic potential of herbal drugs. JIMSA. 2011;24(2):79–81.
- 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
- 283.11 Hemolytic-uremic syndrome
- 580.89 Acute glomerulonephritis with other specified pathological lesion in kidney
- 580.9 Acute glomerulonephritis with unspecified pathological lesion in kidney
- 584.5 Acute kidney failure with lesion of tubular necrosis
- 584.9 Acute kidney failure, unspecified
- 866.00 Injury to kidney without mention of open wound into cavity, unspecified injury
- 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
- 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.
Pratha Muthiah, MD, MPH
Jason Chao, MD, MS
- International Society of Nephrology. Summary of recommendation statements. Kidney Int Suppl (2011). 2012;2(1):8–12. [PMID:25018916]
- Wang HE, Muntner P, Chertow GM, et al. Acute kidney injury and mortality in hospitalized patients. Am J Nephrol. 2012;35(4):349–355. [PMID:22473149]
- Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet. 2012;380:756–766. [PMID:15680458]
- Manoeuvrier G, Bach-Ngohou K, Batard E, et al. Diagnostic performance of serum blood urea nitrogen to creatinine ratio for distinguishing prerenal from intrinsic acute kidney injury in the emergency department. BMC Nephrol. 2017;18(1):173. [PMID:23689657]
- Koyner JL, Davison DL, Brasha-Mitchell E, et al. Furosemide stress test and biomarkers for the prediction of AKI severity. J Am Soc Nephrol. 2015;26(8):2023–2031. [PMID:25655065]
- Hickson LJ, Chaudhary S, Williams AW, et al. Predictors of outpatient kidney function recovery among patients who initiate hemodialysis in the hospital. Am J Kidney Dis. 2015;65(4):592–602. [PMID:25500361]
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