What is the KDIGO definition of acute kidney injury, its underlying mechanisms, and the dialysis modalities used for its management?

KDIGO Definition, Mechanisms, and Dialysis Modalities for Acute Kidney Injury

KDIGO Definition of AKI

Acute kidney injury is diagnosed when serum creatinine increases 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/hour for 6 consecutive hours. 1, 2

Staging Criteria

The KDIGO classification stratifies AKI severity into three stages based on the degree of creatinine elevation or urine output decline 1:

• Stage 1: Creatinine rise of 0.3 mg/dL within 48 hours OR 1.5-1.9× baseline within 7 days OR urine output <0.5 mL/kg/h for >6 hours 1

• Stage 2: Creatinine 2.0-2.9× baseline within 7 days OR urine output <0.5 mL/kg/h for >12 hours 1

• Stage 3: Creatinine ≥3.0× baseline within 7 days OR creatinine ≥354 μmol/L (4.0 mg/dL) with acute rise ≥0.3 mg/dL OR urine output <0.3 mL/kg/h for 24 hours OR anuria for 12 hours OR initiation of renal replacement therapy 1

Critical Diagnostic Considerations

Small creatinine increases of ≥0.3 mg/dL are independently associated with approximately fourfold increased hospital mortality, establishing that patients die "from AKI" not merely "with AKI." 1

The diagnosis requires meeting ANY single criterion—either creatinine-based or urine output-based—with staging determined retrospectively by the highest severity criterion met 1. Progressive staging strongly correlates with escalating mortality risk 1.

Important Pitfalls

• Baseline creatinine determination: Use the most recent known value from medical records rather than imputation methods; when unavailable, back-calculate using MDRD equation assuming GFR of 75 mL/min/1.73 m² 3

• Volume dilution effect: Massive fluid resuscitation can dilute serum creatinine concentration, potentially masking significant GFR reduction 3

• Cirrhotic patients: Baseline creatinine underestimates true GFR due to reduced muscle mass; focus exclusively on creatinine changes rather than urine output, as these patients exhibit avid sodium retention with oliguria despite relatively preserved GFR 4, 3

• Diuretic confounding: Urine output criteria become unreliable in patients receiving diuretics or those with cirrhosis and ascites 3

Mechanisms of Acute Kidney Injury

AKI represents a syndrome with multiple etiologic pathways that must be systematically classified 4:

Prerenal AKI (Functional)

• Results from reduced renal perfusion without intrinsic parenchymal damage 4
• Characterized by urine sodium <20 mEq/L or fractional excretion of sodium (FENa) <1% 4
• Reversible with restoration of adequate perfusion 4

Intrinsic Renal AKI (Structural)

• Acute tubular necrosis (ATN): Most common intrinsic cause, identified by muddy-brown granular casts on urinalysis and urine sodium >40 mEq/L or FENa >2% 4
• Acute interstitial nephritis: Suggested by white blood cell casts and often medication-related 4
• Glomerulonephritis: Indicated by red blood cell casts, hematuria (>50 RBCs/hpf), and proteinuria (>500 mg/day) 3

Postrenal AKI (Obstructive)

• Caused by urinary tract obstruction requiring immediate imaging evaluation 4, 5
• Renal ultrasound should be obtained urgently to rule out obstructive uropathy 5

Common Precipitants

Nephrotoxic medications represent a critical and modifiable cause—NSAIDs, ACE inhibitors, ARBs, diuretics, aminoglycosides, and contrast agents must be identified and discontinued immediately upon AKI diagnosis. 4, 5

The "triple whammy" combination of NSAIDs, diuretics, and ACE inhibitors/ARBs more than doubles AKI risk and must be avoided 5. In cirrhotic patients, infection (particularly spontaneous bacterial peritonitis) is a major precipitant requiring diagnostic paracentesis and empiric broad-spectrum antibiotics when strongly suspected 4.

Dialysis Modalities for AKI Management

Indications for Urgent Renal Replacement Therapy

Initiate RRT emergently for severe oliguria unresponsive to fluid resuscitation, life-threatening hyperkalemia, severe metabolic acidosis, uremic complications (pericarditis, encephalopathy, bleeding), or refractory fluid overload causing pulmonary edema. 4, 5

Delaying RRT when clear indications exist significantly increases mortality 4, 5.

Available RRT Modalities

While the KDIGO guidelines acknowledge that different modalities exist to provide effective therapy with low adverse effect rates 6, specific modality selection depends on hemodynamic stability, institutional resources, and clinical context 6:

• Intermittent hemodialysis: Appropriate for hemodynamically stable patients requiring efficient solute and volume removal 6

• Continuous renal replacement therapy (CRRT): Preferred for hemodynamically unstable critically ill patients, allowing gradual fluid and solute removal with better hemodynamic tolerance 6

• Sustained low-efficiency dialysis (SLED): Hybrid approach offering advantages of both modalities 6

RRT Management Principles

• Reassess the need for continued RRT daily as kidney function may recover 4, 5
• Monitor serum electrolytes, BUN, and creatinine every 4-6 hours initially during acute phase 4, 5
• Avoid overly rapid correction of severe hyponatremia to prevent osmotic demyelination syndrome 5
• Track strict fluid balance with input/output measurements 5

Critical Management Algorithm

1. Immediate actions upon AKI diagnosis: Discontinue all nephrotoxic medications (ACE inhibitors, ARBs, NSAIDs, diuretics) 4, 5

2. Determine etiology: Perform urinalysis with microscopy, measure urine sodium/FENa, obtain renal ultrasound if obstruction suspected 4

3. Assess volume status: Clinical examination ± central venous pressure monitoring; provide isotonic crystalloid resuscitation if hypovolemic, implement fluid restriction if volume-overloaded 4, 5

4. Hemodynamic optimization: Maintain mean arterial pressure >65 mmHg to ensure renal perfusion 4

5. Infection evaluation: Obtain blood cultures, urine cultures, chest radiograph; perform diagnostic paracentesis in cirrhotic patients 4

6. Initiate RRT if indicated: Do not delay when urgent indications present 4, 5

7. Medication adjustment: Dose all medications based on reduced GFR and reassess frequently as kidney function changes 5

Special Cirrhosis Considerations

In cirrhotic patients with AKI, administer albumin 1 g/kg/day (maximum 100 g) for 2 consecutive days when creatinine doubles from baseline 4. Hold diuretics and beta-blockers immediately upon AKI diagnosis 4. For hepatorenal syndrome-AKI, combine albumin (1 g/kg IV day 1, then 20-40 g daily) with vasoactive agents (terlipressin preferred; alternatives include octreotide plus midodrine or norepinephrine) 4.