What are the key symptoms, definition, classification, and risk factors of Acute Kidney Injury (AKI)?

Acute Kidney Injury: Key Clinical Features, Definition, Classification, and Risk Factors

Key Symptoms and Clinical Findings Suggesting AKI

AKI often presents without specific symptoms, making laboratory monitoring and clinical context essential for detection. 1

Clinical Manifestations

• Oliguria (urine output <0.5 mL/kg/h for ≥6 hours) is a cardinal sign, though AKI can occur with normal urine output 1
• Volume overload manifesting as peripheral edema, pulmonary edema, or jugular venous distension 1
• Fluid depletion signs including poor peripheral perfusion, prolonged capillary refill, tachycardia, hypotension, or postural hypotension 1
• Metabolic derangements such as hyperkalemia, metabolic acidosis, and uremia 1
• Hematuria and proteinuria may indicate intrinsic renal causes, particularly glomerular disease 1, 2

Laboratory Findings

• Rising serum creatinine is the primary diagnostic marker, though it lags behind actual GFR decline 1
• Elevated blood urea nitrogen (BUN) accompanies creatinine elevation 1
• Electrolyte abnormalities including hyperkalemia, hyponatremia, or hypernatremia 1
• Abnormal urinalysis with cellular casts (particularly renal tubular epithelial cell casts suggesting acute tubular necrosis) 2

---

KDIGO Definition of AKI

AKI is defined by KDIGO criteria as ANY of the following: 1, 2

1. Increase in serum creatinine ≥0.3 mg/dL within 48 hours, OR
2. Increase in serum creatinine to ≥1.5 times baseline (known or presumed to have occurred within prior 7 days), OR
3. Urine volume <0.5 mL/kg/h for 6 consecutive hours 1

Critical Points About the Definition

• Even small creatinine increases (≥0.3 mg/dL) are independently associated with approximately fourfold increase in hospital mortality 1, 2, 3
• The definition requires meeting only ONE criterion, not all three 2
• Baseline creatinine may be unknown; in such cases, estimate baseline using MDRD equation assuming GFR of 75 mL/min per 1.73 m² 1
• Urine output criteria may be unreliable in patients with cirrhosis/ascites (who may be oliguric despite normal GFR) or those on diuretics 1, 2

---

AKI Staging (KDIGO Classification)

AKI severity is staged 1-3 based on the most severe criterion met: 1, 2

Stage 1

• Creatinine: 1.5-1.9 times baseline OR increase ≥0.3 mg/dL 2, 3
• Urine output: <0.5 mL/kg/h for 6-12 hours 2, 3

Stage 2

• Creatinine: 2.0-2.9 times baseline 2, 3
• Urine output: <0.5 mL/kg/h for ≥12 hours 2, 3

Stage 3

• Creatinine: ≥3.0 times baseline OR increase to ≥4.0 mg/dL (when rise is >0.3 mg/dL or >50%) OR initiation of renal replacement therapy 2, 3
• Urine output: <0.3 mL/kg/h for ≥24 hours OR anuria for ≥12 hours 2, 3

Progression through AKI stages strongly correlates with increased mortality 2, 3

---

Classification by Etiology (Prerenal, Intrinsic, Post-renal)

AKI is categorized into three pathophysiologic types, though most cases are multifactorial: 1, 4

Prerenal AKI (Hemodynamic/Functional)

Caused by impaired renal perfusion without structural kidney damage 1, 4

• Hypovolemia: Hemorrhage, gastrointestinal losses, burns, diuretic overuse 1, 4
• Decreased cardiac output: Heart failure, cardiogenic shock, arrhythmias 1, 5
• Systemic vasodilation: Sepsis, anaphylaxis, cirrhosis with hepatorenal syndrome 1
• Renal vasoconstriction: NSAIDs, ACE inhibitors, ARBs, calcineurin inhibitors 1
• Renal artery occlusion: Thrombosis, embolism, dissection 1

Diagnostic clues for prerenal AKI: 6

• FENa <1% (if not on diuretics; sensitivity 95%, specificity 91%)
• FEUrea <35% (useful if on diuretics; specificity 82%)
• Urine sodium <10 mEq/L
• Caveat: In cirrhotic patients, FENa <1% has 100% sensitivity but only 14% specificity, making it nearly useless; use FEUrea <28.16% instead (75% sensitivity, 83% specificity) 6

Intrinsic (Intrarenal) AKI

Results from direct kidney parenchymal damage 1, 4

Acute Tubular Necrosis (ATN) - Most Common

• Ischemic ATN: Prolonged prerenal state, shock, surgery 4
• Nephrotoxic ATN: Aminoglycosides, contrast agents, cisplatin, rhabdomyolysis (myoglobin), hemolysis 1, 4

Glomerular Disease

• Acute glomerulonephritis: Post-infectious, vasculitis, lupus nephritis 1, 4
• Diagnostic clue: Hematuria (>50 RBCs/hpf), proteinuria (>500 mg/day), RBC casts 2

Interstitial Disease

• Acute interstitial nephritis: Antibiotics (beta-lactams, sulfonamides), NSAIDs, PPIs, autoimmune disease 1, 4
• Diagnostic clue: Eosinophiluria, white blood cell casts 4

Vascular Disease

• Thrombotic microangiopathy, renal vein thrombosis, atheroembolic disease 1, 4

Diagnostic clues for intrinsic AKI: 2, 6

• FENa >1% (suggests ATN)
• Renal tubular epithelial cell casts (pathognomonic for ATN)
• Muddy brown casts
• Lack of response to fluid resuscitation

Postrenal AKI (Obstructive)

Caused by urinary tract obstruction 1, 4

• Upper tract: Bilateral ureteral obstruction (stones, malignancy, retroperitoneal fibrosis) or unilateral obstruction in solitary kidney 1
• Lower tract: Bladder outlet obstruction (prostatic hypertrophy, neurogenic bladder, bladder cancer), urethral obstruction 1

Postrenal causes account for <3% of AKI cases 1

Diagnostic approach: 1

• Renal ultrasound to evaluate for hydronephrosis (recommended when risk factors present: older male with prostatic hypertrophy, pelvic malignancy, single kidney) 1, 7
• Bladder catheterization to assess for urinary retention

---

Common Risk Factors for AKI

Multiple risk factors often coexist, increasing AKI susceptibility: 1

Patient-Related Risk Factors

• Age ≥65 years 1
• Chronic kidney disease (any stage, but especially stage 4 or higher) 1, 7
• Diabetes mellitus 1
• Heart failure or reduced cardiac output 1
• Liver disease/cirrhosis 1
• History of prior AKI 1
• Sepsis or systemic infection 1
• Hypovolemia/dehydration 1
• Hypotension or shock 1, 5

Exposure-Related Risk Factors

• Nephrotoxic medications: NSAIDs, ACE inhibitors, ARBs, aminoglycosides, vancomycin, contrast agents, chemotherapy 1
• Diuretic use (especially if causing volume depletion) 1
• Recent surgery (particularly cardiac or major abdominal surgery) 1
• Critical illness requiring ICU admission (30-60% of critically ill patients develop AKI) 1, 8
• Rhabdomyolysis (trauma, prolonged immobilization, statins) 4

Clinical Context Risk Factors

• Hospital-acquired AKI is 5-10 times more common than community-acquired AKI 1
• Cardiogenic shock: AKI incidence up to 80%, with 13% requiring dialysis 5
• Acute heart failure: AKI incidence 13-36% 5
• COVID-19: 31% of ventilated patients and 4% of non-ventilated patients required renal replacement therapy 1

Common Pitfalls in Risk Assessment

• Fever and increased respiratory rate increase insensible fluid losses, predisposing to volume depletion 1
• Treatments for underlying conditions may themselves increase AKI risk (e.g., diuretics causing hypovolemia) 1
• Maintaining optimal fluid status (euvolaemia) is critical but difficult to achieve, as both hypovolemia and fluid overload worsen outcomes 1
• Multiple nephrotoxic drugs used simultaneously exponentially increase risk 1