BASICS
DESCRIPTION
Abrupt loss of kidney function is defined as a rise in serum creatinine (SCr) of ≥0.3 mg/dL within 48 hours, or a 50% increase in SCr within 7 days, or oliguria 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).
EPIDEMIOLOGY
Incidence
5% of hospital and 30% of ICU admissions have a diagnosis of acute kidney injury (AKI). 25% of patients develop AKI while in the hospital, and 50% of those cases are iatrogenic. Development of AKI in the inpatient setting is associated with a >4-fold increased risk of death (2).
ETIOLOGY AND PATHOPHYSIOLOGY
Can be divided into three categories: prerenal, intrarenal, and postrenal based on BUN/creatinine ratio
- Prerenal (BUN/creatinine ratio ≥20:1; ~55%)
- Hypotension, volume depletion (GI losses, excessive sweating, diuretics, hemorrhage); renal artery stenosis/embolism; burns; heart failure; liver failure
- Secondary to decreased renal perfusion (often due to hypovolemia) leading to a decrease in glomerular filtration rate (GFR); reversible if factors decreasing perfusion are corrected; otherwise, it can progress to an intrarenal pathology known as ischemic acute tubular necrosis.
- Intrarenal (BUN/creatinine <10:1; ~40%)
- Acute tubular necrosis (ATN) (from prolonged prerenal state, radiographic contrast material, aminoglycosides, NSAIDs, or other nephrotoxic substances); glomerulonephritis (GN); acute interstitial nephritis (drug-induced); arteriolar insults; vasculitis; accelerated hypertension; cholesterol embolization (common after arterial procedures); intrarenal deposition/sludging (uric acid nephropathy and multiple myeloma [Bence-Jones proteins])
- Postrenal (BUN/creatinine 10 to 20:1; ~5%)
- 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)
- Secondary to extrinsic (e.g., BPH) or intrinsic (e.g., stones) obstruction of the urinary collection system
Genetics
No known genetic pattern
RISK FACTORS
- Chronic kidney disease (CKD)
- Comorbid conditions (e.g., diabetes, hypertension, heart failure, liver failure) (3)
- Advanced age
- Radiographic contrast material exposure
- Medications that impair autoregulation of GFR (NSAIDs, ACE-I/ARB, cyclosporine/tacrolimus)
- Nephrotoxic medications (e.g., aminoglycoside antibiotics, platinum-based chemotherapy)
- Volume depletion (e.g., diuretics, hemorrhage, GI losses)
- Sepsis (4)
- Surgery
- Rhabdomyolysis
- Solitary kidney (risk in nephrolithiasis)
- BPH
- Malignancy (e.g., multiple myeloma)
GENERAL PREVENTION
See "Treatment; General Measures."¯
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
DIAGNOSIS
HISTORY
- General: PO intake, urine output, body weight, baseline creatinine (to assess magnitude of change), and medication use
- Prerenal: thirst, orthostatic dizziness
- Intrarenal: nephrotoxic medications, radiocontrast material, other toxins
- Fever, arthralgias, and pruritic rash suggest allergic interstitial nephritis (AIN); although this triad is only present in 10% of cases.
- Edema, hypertension, and oliguria with nephritic urine sediment (RBCs and RBC casts) point to glomerulonephritis or vasculitis
- Livedo reticularis, SC nodules, and ischemic digits despite good pulses suggest atheroembolization.
- Flank pain suggests occlusion of the renal artery or vein.
- Postrenal: Colicky flank pain that radiates to the groin suggests a 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; ask about anticholinergic drugs that could lead to neurogenic bladder.
- Uremic Sx: lethargy, nausea/vomiting, anorexia, pruritus, restless legs, sleep disturbance, hiccups
PHYSICAL EXAM
- 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; look for stigmata of associated comorbid conditions such as liver and heart failure, as well as sepsis.
- Intrinsic renal signs: pruritic rash, livedo reticularis, SC nodules, ischemic digits despite good pulses
- Postrenal signs: suprapubic distension, flank pain, enlarged prostate
DIFFERENTIAL DIAGNOSIS
See "Etiology."¯
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Urinalysis: dipstick for blood and protein; microscopy for cells, casts, and crystals
- Casts: transparent hyaline casts-prerenal etiology; pigmented granular/muddy brown casts-ATN; WBC casts-acute interstitial nephritis; RBC casts-GN
- Urine eosinophils: ≥1% eosinophils by Hansel stain suggestive of acute interstitial nephritis (sensitivity, 67%; specificity, 83%)
- Urine electrolytes in an oliguric state
- FENa = [(UNa — PCr)/(PNa — UCr)] — 100, where U = urine, P = plasma, Na = sodium, Cr = creatinine; FENa <1%, likely prerenal; >2%, likely intrarenal
- If patient is on diuretics, use FEurea instead of FENa: FEurea = [(Uurea — PCr)/(PBUN — UCr)] — 100; FEurea <35% suggests prerenal etiology (5)[B].
- CBC, BUN, SCr, electrolytes (including Ca/Mg/P); consider arterial blood gases (ABGs).
- Common lab abnormalities in AKI
- Increased: K+, phosphate, Mg, uric acid
- Decreased: Hct, Na, Ca
- Calculate creatinine clearance (CrCl) to ensure that medications are dosed appropriately.
- Cockcroft-Gault equation for CrCl (mL/min) = (140-age) — (weight in kilograms) — (0.85 if female)/(72 — serum creatinine)
- Note that estimating equations of CrCl/GFR are only valid when renal function (SCr) is at steady-state; anuria implies CrCl of 0.
- Renal ultrasound (US): first-line; excludes postrenal causes if negative; 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
- Several novel biomarkers such as urinary IL-18, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and plasma cystatin C, are currently being validated for their role in the initial evaluation and management of AKI (6)[C].
Follow-Up Tests & Special Considerations
- Consider CK (if suspect rhabdomyolysis) and immunologic testing (if suspect GN/vasculitis).
- More advanced imaging techniques should be considered if initial tests do not reveal etiology.
- Prerenal: ultrasound as effective as CT for evaluating for obstruction
- Noncontrast helical CT scan: considered most sensitive study for detecting nephrolithiasis
- Radionucleotide renal scan: evaluates renal perfusion, function (GFR), and presence of obstructive uropathy and extravasation
- MRI: Acute tubulointerstitial nephritis can show an increased T2-weighted signal. Gadolinium contrast is contraindicated if GFR <30 mL/min due to risk of nephrogenic systemic fibrosis.
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 other tests; do not reveal a diagnosis; most useful for evaluation of intrinsic AKI of unclear cause, such as AIN, GN, vasculitis, or renal transplant rejection
TREATMENT
GENERAL MEASURES
Identify and correct all prerenal and postrenal causes.
- Stop nephrotoxic drugs and renally dose others.
- Strictly record intake/output and daily weights.
- Optimize cardiac output to maintain renal perfusion.
- Follow nutrition suggestions and be aware of infections; treat aggressively if they occur.
- Avoid aspirin to reduce bleeding tendency.
- Indications for initiating hemodialysis in patients with AKI: volume overload, severe or progressive hyperkalemia, or severe metabolic acidosis refractory to medical management; advanced uremic complications (pericarditis, encephalopathy, bleeding diathesis)
MEDICATION
First Line
- Focus on treating the underlying cause and associated complications.
- Monitor and adjust fluids and electrolytes to prevent fluid overload, hyperkalemia, hyperphosphatemia, and hypermagnesemia.
- If patient is oliguric and not volume overloaded, a fluid challenge may be appropriate with diligent monitoring for volume overload.
- Furosemide is ineffective in preventing and treating AKI (7)[A] but can judiciously be used to manage volume overload and/or hyperkalemia.
- Dopamine, natriuretic peptides, insulin-like growth factor, and thyroxine also have no benefit in the treatment of AKI.
- Fenoldopam, a dopamine agonist, has been equivocal in decreasing risk of RRT and mortality in setting of AKI; not currently recommended for use, large RCT in progress (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; be aware of volume overload, hypocalcemia, hypokalemia.
- Effective strategies for AKI prevention: IV isotonic hydration, once-daily dosing of aminoglycosides (8)[A]; use of lipid formulations of amphotericin B, use of iso-osmolar nonionic contrast media
- Risk of contrast-induced AKI may be 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 (9)[B]. N-acetylcysteine, although previously recommended, shown to have no benefit in recent large-scale RCT (10)[A].
Second Line
- Tamsulosin or other selective Ī±-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
SURGERY/OTHER PROCEDURES
- Relief of obstruction with retrograde ureteral catheters/percutaneous nephrostomy
- Hemodialysis catheter placement
COMPLEMENTARY & ALTERNATIVE MEDICINE
Many herbal and dietary supplements can be nephrotoxic (aristolochic acid, licorice [Glycyrrhiza glabra], ephedra, star fruit [Averrhoa carambola], others).
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Most patients with AKI will require admission; consider discharge in a stable patient with mild AKI and a clearly identified, reversible cause.
- Evaluate for and treat potentially life-threatening complications: hyperkalemia, metabolic acidosis, volume overload, advanced uremia
- If volume depleted, give isotonic IV fluids.
- Place a Foley catheter.
IV Fluids
Isotonic fluids should be used to treat hypovolemia.
Nursing
Place a Foley catheter; strict I/Os, daily weights
Discharge Criteria
Stabilization of renal function and a concrete plan for continued treatment, if necessary
Some patients may require dialysis until renal recovery.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Nephrology follow-up if persistent renal impairment and/or proteinuria
DIET
- Total caloric intake should be 20 to 30 kcal/kg/day to avoid catabolism (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
Keep well-hydrated. Avoid nephrotoxic drugs, such as NSAIDs and aminoglycosides.
PROGNOSIS
- Depending on the cause, comorbid conditions, and age of patient, mortality ranges from 5% to 80%
- In cases of prerenal and postrenal failure, very good rates of recovery are positively correlated with shorter duration of AKI. Intrarenal etiologies usually take more time to recover. Overall, average recovery takes from days to months.
- Even with complete recovery from AKI, affected patients are at higher subsequent risk of developing CKD and ESRD (11).
COMPLICATIONS
Death, sepsis, infection, seizures, paralysis, peripheral edema, CHF, arrhythmias, uremic pericarditis, bleeding, hypotension, anemia, hyperkalemia, uremia
REFERENCES
11 International Society of Nephrology. Summary of recommendation statements. Kidney Int Suppl. 2012;2(1):8-12.22 Wang HE, Muntner P, Chertow GM, et al. Acute kidney injury and mortality in hospitalized patients. Am J Nephrol. 2012;35(4):349-355.33 Hilton R. Acute renal failure. BMJ. 2006;333(7572):786-790.44 Lameire N. The pathophysiology of acute renal failure. Crit Care Clin. 2005;21(2):197-210.55 Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet. 2005;365(9457):417-430.66 McCullough PA, Kellum JA, Mehta RL, et al. ADQI consensus on AKI biomarkers and cardiorenal syndromes. Contrib Nephrol. 2013;182:45-64.77 Ho KM, Sheridan DJ. Meta-analysis of frusemide to prevent or treat acute renal failure. BMJ. 2006;333(7565):420.88 Venkataraman R, Kellum JA. Prevention of acute renal failure. Chest. 2007;131(1):300-308.99 Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004;291(19):2328-2334.1010 ACT Investigators. Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized Acetylcysteine for Contrast-induced nephropathy Trial (ACT). Circulation. 2011;124(11):1250-1259.1111 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.
SEE ALSO
- Glomerulonephritis, Acute; Hepatorenal Syndrome; Hyperkalemia; Prostatic Hyperplasia, Benign (BPH); Chronic Kidney Disease; Reye Syndrome; Rhabdomyolysis; Sepsis
- Algorithm: Anuria or Oliguria
CODES
ICD10
- N17.9 Acute kidney failure, unspecified
- N17.0 Acute kidney failure with tubular necrosis
- N00.9 Acute nephritic syndrome with unsp morphologic changes
- N10 Acute tubulo-interstitial nephritis
- S37.009A Unspecified injury of unspecified kidney, initial encounter
- D59.3 Hemolytic-uremic syndrome
ICD9
- 584.9 Acute kidney failure, unspecified
- 584.5 Acute kidney failure with lesion of tubular necrosis
- 580.9 Acute glomerulonephritis with unspecified pathological lesion in kidney
- 580.89 Acute glomerulonephritis with other specified pathological lesion in kidney
- 283.11 Hemolytic-uremic syndrome
- 866.00 Injury to kidney without mention of open wound into cavity, unspecified injury
SNOMED
- 14669001 Acute renal failure syndrome (disorder)
- 35455006 Acute tubular necrosis (disorder)
- 19351000 Acute glomerulonephritis (disorder)
- 28637003 Acute interstitial nephritis (disorder)
- 111407006 Hemolytic uremic syndrome (disorder)
- 40095003 injury of kidney (disorder)
CLINICAL PEARLS
- Three categories of AKI: prerenal, intrarenal, and postrenal
- Prerenal: decreased renal perfusion (often from hypovolemia) leading to a decrease in GFR; reversible if perfusion is restored
- Intrarenal: intrinsic kidney damage; ATN is the most common cause via ischemic/nephrotoxic injury to the kidney.
- Postrenal: secondary to extrinsic/intrinsic obstruction of the urinary collection system
- Recognize the need 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