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 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 as an inpatient associated with >4-fold increased risk of death (2).
Etiology and Pathophysiology
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
- 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.
- Intrarenal (BUN/creatinine <10:1; ~40%)
- Acute tubular necrosis (ATN) (from prolonged prerenal azotemia, radiographic contrast material, aminoglycosides, NSAIDs, or other nephrotoxic substances); glomerulonephritis (GN); acute interstitial nephritis (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 (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) leading to obstruction of the urinary collection system
No known genetic pattern
- Chronic kidney disease (CKD)
- Comorbid conditions (e.g., diabetes, hypertension, heart failure, liver failure)
- Advanced age
- Radiocontrast material exposure (intravascular)
- Medications that impair autoregulation of GFR (NSAIDs, ACE-I/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)
See “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
- General: PO intake, urine output, body weight, medication use
- Prerenal: thirst, orthostatic symptoms
- Intrarenal: nephrotoxic medications, radiocontrast material, other toxins
- Fever, arthralgias, and pruritic rash suggest allergic interstitial nephritis (AIN).
- 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
- 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/GFR) if at all possible.
- 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 suggests acute interstitial nephritis (poor sensitivity)
- Urine electrolytes in an oliguric state
- 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 appropriate medications 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 (4)[C]
Follow-Up Tests & Special Considerations
- Consider CK (rhabdomyolysis) and immunologic testing (if suspect GN/vasculitis).
- 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. 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)
Identify and correct prerenal and postrenal causes.
- Stop nephrotoxic drugs and renally dose others.
- Strict intake/output and daily weight recordings
- Optimize cardiac output to maintain renal perfusion.
- Optimize nutrition and treat any infections.
- Indications for hemodialysis: 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, correct electrolyte imbalances—hyperkalemia, hyperphosphatemia, and hypermagnesemia.
- 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 dialysis, 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 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; 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
- Relief of obstruction with retrograde ureteral catheters/percutaneous nephrostomy
- Hemodialysis catheter placement
Complementary and Alternative Medicine
Many herbal and dietary supplements can be nephrotoxic (aristolochic acid, ochratoxin A, Djenkol bean, impila, orellanine, cat’s claw).
- Most patients with AKI require admission.
- Evaluate for and treat potentially life-threatening complications: hyperkalemia, metabolic acidosis, volume overload, advanced uremia.
- If hypovolemic, give isotonic IV fluids.
- Monitor strict I/Os, daily weights.
- Consider bladder catheter to quantify urine output.
- Stabilize renal function and ensure a concrete 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 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.
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 failure, 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 ESRD.
Death, sepsis, infection, seizures, paralysis, peripheral edema, CHF, arrhythmias, uremic pericarditis, bleeding, hypotension, anemia, hyperkalemia, uremia
- 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. [PMID:21859972]
- 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]
- Singh NP, Prakash A. Nephrotoxic potential of herbal drugs. JIMSA. 2011;24(2):79–81.
- Venkataraman R, Kellum JA. Prevention of acute renal failure. Chest. 2007;131(1):300–308. [PMID:17218591]
- D59.3 Hemolytic-uremic syndrome
- N00.9 Acute nephritic syndrome with unsp morphologic changes
- N10 Acute tubulo-interstitial nephritis
- N17.0 Acute kidney failure with tubular necrosis
- N17.9 Acute kidney failure, unspecified
- S37.009A Unspecified injury of unspecified kidney, initial encounter
- 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
- 111407006 Hemolytic uremic syndrome (disorder)
- 14669001 Acute renal failure syndrome (disorder)
- 19351000 Acute glomerulonephritis (disorder)
- 28637003 Acute interstitial nephritis (disorder)
- 35455006 Acute tubular necrosis (disorder)
- 40095003 injury of kidney (disorder)
- Three categories of AKI:
- Prerenal: decreased renal perfusion (often from hypovolemia) leading to a decrease in GFR; reversible if perfusion is restored
- 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 speed recovery.
Jason Kurland, MD
- International Society of Nephrology. Summary of recommendation statements. Kidney Int Suppl. 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]
- Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet. 2005;365(9457):417–430. [PMID:15680458]
- 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]
- 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]
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