Acute kidney injury

Definition

Acute kidney injury (AKI; formerly acute renal failure) is a rapid decline in kidney function over days to weeks with a rise in blood creatinine and urea (azotemia), with or without a fall in urine output. According to KDIGO, AKI is present in case of:

• a rise in serum creatinine by ≥ 0.3 mg/dL (26.5 µmol/L) within 48 hours, or
• a rise to ≥ 1.5 times baseline within the prior 7 days, or
• urine output < 0.5 mL/kg/h for 6 hours

Classification

KDIGO stages and types

• Stage 1: creatinine 1.5 to 1.9 times baseline or a rise of ≥ 0.3 mg/dL; urine < 0.5 mL/kg/h for 6–12 hours
• Stage 2: creatinine 2.0 to 2.9 times baseline; urine < 0.5 mL/kg/h for ≥ 12 hours
• Stage 3: creatinine ≥ 3 times baseline or ≥ 4.0 mg/dL (353.6 µmol/L); urine < 0.3 mL/kg/h for ≥ 24 hours or anuria for ≥ 12 hours

By cause, prerenal, intrinsic renal and postrenal AKI are distinguished; by urine volume, oliguric (< 500 mL/day) and nonoliguric courses.

Occurrence & epidemiology

AKI is a common organ dysfunction in hospital inpatients, particularly in sepsis, major trauma and circulatory failure. Prerenal AKI and acute tubular injury are the most common causes in this setting.

Aetiopathogenesis

Causes

• Prerenal (reduced renal perfusion of intact tissue): volume depletion (vomiting, diarrhea, hemorrhage, burns), heart failure and cardiogenic shock, sepsis, decompensated liver cirrhosis, drugs such as NSAIDs. The kidney retains sodium and water; sustained hypoperfusion progresses to ischemic tubular injury.
• Intrinsic renal: acute tubular necrosis (mostly ischemic; toxic e.g. due to aminoglycosides, iodinated contrast media, myoglobin in rhabdomyolysis, hemoglobin in hemolysis), glomerulonephritis (ANCA-associated, anti-GBM, immune complex), acute interstitial nephritis and vascular disorders (atheroembolism, thrombotic microangiopathy, malignant hypertension).
• Postrenal: obstruction between the tubules and the urethra, including microscopic obstruction within the tubules by precipitating crystals or proteins (e.g. uric acid, myeloma light chains); back pressure reduces glomerular filtration. Ureteral obstruction causes AKI only if bilateral or in a single kidney. The most common cause of sudden urinary retention in men is prostatic enlargement; other causes are calculi, tumors and neurogenic bladder disorders.

Clinical features

Symptoms

Symptoms of the underlying illness often predominate. Early signs are falling urine output, weight gain and edema; as uremia progresses, anorexia, nausea, vomiting, weakness, myoclonic jerks, confusion, seizures and finally coma follow. Dark, tea-colored urine suggests glomerulonephritis or myoglobinuria, a palpable bladder suggests bladder outlet obstruction.

Course of urine output

Typical is a prodromal phase with usually normal urine output, an oliguric phase with 50–500 mL of urine per day (many patients are never oliguric) and a polyuric recovery phase in which sodium wasting and polyuria may persist for days to weeks.

Complications

• hyperkalemia with cardiac arrhythmias
• fluid overload up to pulmonary edema
• metabolic acidosis, hyperphosphatemia, hypocalcemia
• uremic pericarditis, encephalopathy and bleeding tendency

Diagnosis

Laboratory tests

• Creatinine and urea rise day by day, creatinine by up to 2 mg/dL (180 µmol/L) daily. GFR estimating equations are unreliable while creatinine is unstable.
• Electrolytes and blood gases: hyperkalemia, hyperphosphatemia, hypocalcemia, usually moderate hyponatremia (125–135 mmol/L), metabolic acidosis with bicarbonate usually 15–20 mmol/L
• Blood count: normochromic, normocytic anemia (hematocrit typically 25–30%)
• Depending on suspicion: creatine kinase and myoglobin (rhabdomyolysis), uric acid (tumor lysis), serum protein electrophoresis (myeloma)

Urine findings

In oliguria, urinary indices distinguish prerenal AKI from tubular injury:

• fractional excretion of sodium (FENa) < 1% prerenal, > 1% in tubular injury
• urine sodium < 10 mmol/L prerenal, > 40 mmol/L in tubular injury
• urine-to-plasma osmolality ratio > 1.5 prerenal, 1–1.5 in tubular injury

The urine sediment is bland in prerenal AKI. Tubular epithelial cells and numerous, often brown-pigmented granular casts indicate tubular injury; red blood cell casts and dysmorphic red cells indicate glomerulonephritis or vasculitis.

Imaging

• Postvoid residual volume: > 100 mL indicates inadequate bladder emptying.
• Renal ultrasound: hydronephrosis, kidney size (small kidneys suggest chronic kidney disease). Early obstruction or obstruction with hypovolemia may be missed.
• Noncontrast CT to localize an obstruction, magnetic resonance angiography if renal artery stenosis or vascular thrombosis is suspected

Serology and biopsy

If an intrinsic renal cause is suspected: anti-GBM antibodies, ANCA, antinuclear and anti-dsDNA antibodies, antistreptolysin O titer and complement (C3, C4). If the cause remains unclear, a kidney biopsy clarifies it.

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Acute Kidney Injury (AKI)
2. NICE NG148: Acute kidney injury – Context

Cross-references