What are the classification, grading, and causes of Acute Kidney Injury (AKI)?

Classification and Grading of Acute Kidney Injury

AKI is diagnosed when serum creatinine rises by ≥0.3 mg/dL within 48 hours, OR increases to ≥1.5 times baseline within 7 days, OR urine output falls below 0.5 mL/kg/h for 6 hours, and is staged into three severity levels based on the magnitude of creatinine elevation or duration of oliguria. 1, 2

Definition Criteria (KDIGO)

AKI is defined by any one of the following criteria 1:

• Serum creatinine increase ≥0.3 mg/dL (26.5 µmol/L) within 48 hours 1, 2
• Serum creatinine increase to ≥1.5 times baseline (known or presumed to have occurred within prior 7 days) 1, 2
• Urine output <0.5 mL/kg/h for 6 hours 1

Staging System

Stage 1 1, 2:

• Serum creatinine: 1.5-1.9 times baseline OR ≥0.3 mg/dL increase
• Urine output: <0.5 mL/kg/h for 6-12 hours

Stage 2 1, 2:

• Serum creatinine: 2.0-2.9 times baseline
• Urine output: <0.5 mL/kg/h for ≥12 hours

Stage 3 1, 2:

• Serum creatinine: ≥3.0 times baseline OR ≥4.0 mg/dL (353.6 µmol/L) OR initiation of renal replacement therapy
• In patients <18 years: eGFR decrease to <35 mL/min/1.73 m² 1
• Urine output: <0.3 mL/kg/h for ≥24 hours OR anuria for ≥12 hours

The patient is staged according to the most severe criterion met, whether creatinine or urine output based. 2 Progression through stages correlates strongly with increased mortality 2.

Causes of AKI (Etiologic Classification)

Prerenal AKI (Reduced Renal Perfusion)

Volume depletion 3, 4:

• Hemorrhage, gastrointestinal losses (vomiting, diarrhea), renal losses (diuretics, osmotic diuresis), third-spacing (burns, pancreatitis)

Decreased effective circulating volume 3, 4:

• Heart failure, cirrhosis with hepatorenal syndrome, nephrotic syndrome, sepsis with vasodilation

Renal vasoconstriction 3, 4:

• NSAIDs, ACE inhibitors/ARBs (especially with bilateral renal artery stenosis), hepatorenal syndrome, hypercalcemia

Diagnostic clues: FENa <1% (if not on diuretics), FEUrea <35%, urine sodium <10 mEq/L, though these are unreliable in cirrhotic patients 5

Intrinsic Renal AKI

Acute tubular necrosis (ATN) - most common intrinsic cause 3, 4:

• Ischemic: Prolonged prerenal state, sepsis, surgery (especially cardiac), hypotension
• Nephrotoxic: Aminoglycosides, amphotericin B, contrast media, cisplatin, rhabdomyolysis (myoglobin), hemolysis, tumor lysis syndrome

Acute interstitial nephritis 3, 4:

• Medications (beta-lactams, NSAIDs, PPIs, sulfonamides), infections, autoimmune diseases

Glomerular diseases 3, 4:

• Rapidly progressive glomerulonephritis, lupus nephritis, vasculitis, post-infectious glomerulonephritis

Vascular causes 3, 4:

• Renal artery thrombosis/embolism, renal vein thrombosis, atheroembolic disease, malignant hypertension, thrombotic microangiopathy (HUS/TTP)

Diagnostic clues: FENa >1%, muddy brown casts (ATN), white blood cell casts (interstitial nephritis), red blood cell casts (glomerulonephritis) 4

Postrenal AKI (Obstruction)

Upper urinary tract obstruction (requires bilateral obstruction or single functioning kidney) 3, 4:

• Nephrolithiasis, retroperitoneal fibrosis, tumor compression, blood clots

Lower urinary tract obstruction 3, 4:

• Benign prostatic hyperplasia, prostate cancer, bladder cancer, neurogenic bladder, urethral stricture

Diagnostic approach: Renal ultrasound to evaluate for hydronephrosis in patients with risk factors (older males with prostatic disease, pelvic malignancy, single kidney) 4

Critical Clinical Considerations

Small creatinine increases matter: Even a 0.3 mg/dL rise is independently associated with approximately four-fold increased hospital mortality 2. Electronic urine output monitoring identifies AKI significantly earlier (median 12.75 hours) than creatinine-based criteria alone (median 39.06 hours) 6.

Urine output criteria limitations: In cirrhotic patients with ascites, oliguria may occur despite normal GFR due to avid sodium retention, making urine output criteria unreliable in this population 2, 5. Diuretic use also confounds interpretation 5.

Post-AKI follow-up: Evaluate all patients 3 months after AKI for resolution, new-onset CKD, or worsening of pre-existing CKD, as AKI survivors have increased risk of developing chronic kidney disease 1.

Risk stratification: Patients should be stratified according to susceptibilities (advanced age, CKD, diabetes, heart failure) and exposures (nephrotoxic medications, contrast media, major surgery, sepsis) to enable early detection and preventive interventions 1.