What are the definitions of rapidly progressive renal failure (RPRF), acute kidney injury (AKI), and chronic liver disease (CLD)?

Definitions of RPRF, AKI, and CLD

Acute Kidney Injury (AKI) Definition

AKI is diagnosed when any one of the following KDIGO criteria is met: serum creatinine rise ≥0.3 mg/dL within 48 hours, OR creatinine increase to ≥1.5× baseline within 7 days, OR urine output <0.5 mL/kg/h for ≥6 consecutive hours. 1, 2, 3

KDIGO Staging System

• Stage 1: Creatinine 1.5–1.9× baseline OR absolute increase ≥0.3 mg/dL, OR urine output <0.5 mL/kg/h for 6–12 hours 1, 2, 3
• Stage 2: Creatinine 2.0–2.9× baseline, OR urine output <0.5 mL/kg/h for ≥12 hours 1, 2, 3
• Stage 3: Creatinine ≥3.0× baseline OR ≥4.0 mg/dL (with acute rise ≥0.3 mg/dL), OR initiation of renal replacement therapy, OR urine output <0.3 mL/kg/h for ≥24 hours or anuria ≥12 hours 1, 2, 3

Temporal Classifications

• Rapid reversal of AKI: Complete reversal of KDIGO criteria within 48 hours of onset 1, 3
• Persistent AKI: Continuation of AKI criteria beyond 48 hours from onset 1, 3
• Acute Kidney Disease (AKD): Kidney dysfunction persisting 7–90 days after the initiating event; this fills the gap between AKI (≤7 days) and CKD (>90 days) 1, 3

The AKD definition was proposed to capture patients with GFR <60 mL/min/1.73 m² for <3 months, GFR decrease ≥35%, or creatinine increase ≥50% in <3 months 1. However, the Canadian Society of Nephrology cautions that AKD should be limited to research purposes until its clinical utility is validated, as it may simply represent an artifact of the AKI and CKD timeline definitions 1.

Rapidly Progressive Renal Failure (RPRF) Definition

RPRF is a clinical diagnosis characterized by progressive renal impairment developing over days to weeks, most commonly caused by rapidly progressive glomerulonephritis (RPGN) with crescentic glomerular lesions on biopsy. 4, 5, 6, 7

Key Features

• Time course: Kidney function deteriorates over days to weeks (not hours as in typical AKI, nor months as in CKD) 4, 5, 6, 7
• Clinical presentation: Nephritic sediment (hematuria, red cell casts), proteinuria, oliguria, hypertension, and edema 6, 7
• Histopathology: Necrotizing glomerular lesions with extracapillary proliferation (crescents) in most glomeruli 5, 6, 7

Major Etiologic Categories

• Anti-GBM disease (Goodpasture syndrome) 6, 7
• Pauci-immune disorders (ANCA-associated vasculitis)—the most common cause 6, 8
• Immune complex-mediated (lupus nephritis, post-infectious GN, IgA nephropathy) 4, 6, 7
• Idiopathic/overlap syndromes 6

RPRF represents a nephrological emergency requiring urgent serologic evaluation (ANCA, anti-GBM antibody, complement levels) and kidney biopsy within days to prevent irreversible progression to end-stage kidney disease 4, 5, 6, 7, 8.

Chronic Liver Disease (CLD) Definition

CLD is defined by persistent liver dysfunction or structural abnormalities lasting >6 months, typically manifesting as cirrhosis with portal hypertension, ascites, and hepatic synthetic dysfunction. 1

AKI in Cirrhosis: Special Considerations

The International Club of Ascites adapted KDIGO criteria for cirrhotic patients because baseline creatinine underestimates true GFR due to sarcopenia 1, 2. Key modifications include:

• ICA-AKI criteria: Creatinine rise ≥0.3 mg/dL within 48 hours OR ≥50% from baseline, without the traditional fixed cutoff of 1.5 mg/dL 1, 2
• Hepatorenal syndrome-AKI (HRS-AKI): Renamed from HRS-1; defined as development of Stage ≥2 AKI (regardless of final creatinine) when all other HRS diagnostic criteria are fulfilled, removing the prior 2.5 mg/dL threshold 1
• Urine output is unreliable in cirrhosis due to avid sodium retention and frequent diuretic use 1, 2

Pathophysiology in Cirrhosis

Splanchnic and systemic vasodilation causes effective arterial underfilling, triggering compensatory vasoconstriction (renin-angiotensin-aldosterone, sympathetic activation) that reduces renal blood flow and GFR 1. Bacterial infection is the most common precipitant of AKI in cirrhosis, worsening circulatory dysfunction through cytokine-mediated vasodilation and direct tubular toxicity 1.

Common Pitfalls

• Do not dismiss a 0.3 mg/dL creatinine rise as insignificant: Even Stage 1 AKI confers approximately four-fold higher in-hospital mortality 1, 2, 3
• Do not apply eGFR equations (MDRD, CKD-EPI) during acute creatinine changes: These require steady-state and were validated only in stable CKD 1, 2
• Do not delay kidney biopsy in suspected RPGN: Irreversible glomerular scarring develops within days to weeks 4, 5, 6, 7
• In cirrhosis, do not rely on fixed creatinine thresholds or urine output alone: Use ICA-AKI criteria and assess for infection promptly 1, 2