AKI Staging & Classification: KDIGO Framework
KDIGO 2026 Three-Axis Staging System (C/U/B)
KDIGO 2026 replaces the single-axis staging system with three independent axes: Creatinine (C), Urine Output (U), and Biomarkers (B). Each axis is staged separately. AKI is present when any axis is ≥1.
Creatinine Axis (C0–C3)
| Stage | Cr Criteria |
|---|---|
| C0 | No creatinine-based AKI |
| C1 | 1.5–1.9× baseline within 7 days OR ≥0.3 mg/dL rise within 48 hours |
| C2 | 2.0–2.9× baseline |
| C3 | ≥3.0× baseline OR ≥4.0 mg/dL rise OR initiation of RRT |
Urine Output Axis (U0–U3)
| Stage | UO Criteria |
|---|---|
| U0 | No urine output–based AKI |
| U1 | <0.5 mL/kg/h for 6–12 hours |
| U2 | <0.5 mL/kg/h for ≥12 hours |
| U3 | <0.3 mL/kg/h for ≥24 hours OR anuria ≥12 hours |
Biomarker Axis (B0/B1)
| Stage | Biomarker Criteria |
|---|---|
| B0 | No biomarker evidence of kidney injury |
| B1 | Positive kidney injury/stress biomarker (e.g., TIMP-2·IGFBP7, NGAL) per guideline Rec 2.4.1 (2B) |
Subclinical AKI (C0/U0/B1)
A critical new category: kidney injury/stress detected by biomarkers without creatinine rise or oliguria. This identifies patients at risk who would have been missed entirely by the 2012 criteria.
Cystatin C as Alternative Functional Criterion
When serum creatinine is unreliable (low muscle mass, extremes of body habitus, liver disease, fluid overload), cystatin C may be used: a rise of ≥1.5× baseline within 7 days satisfies the functional criterion for AKI.
Key Insight
- Stage each axis independently — a patient can be C1/U2/B1 (moderate by UO, mild by Cr, biomarker-positive)
- The highest axis determines overall severity for clinical decision-making
- Oliguria (<0.5 mL/kg/h) indicates severity independent of Cr; use ALL THREE metrics
- Once Stage 3 on any axis, patient stays Stage 3 even if that parameter improves slightly
Mechanistic Classification: Prerenal → Intrinsic → Postrenal
Prerenal AKI (~55% of AKI)
Inadequate renal perfusion; glomerular filtration ↓ but tubules intact.
Mechanism: Volume depletion → ↓ renal perfusion pressure → ↓ GFR
Reversibility: Excellent if caught early; becomes intrinsic AKI if prolonged
Biomarkers: - FeNa < 1% (sodium fractional excretion < 1% suggests volume-responsive) - FeUrea < 35% (better in diuretic users, CKD baseline; > prerenal even if FeNa >1%) - High BUN:Cr ratio (>20:1 suggests prerenal)
FeNa pitfalls: Falsely elevated in: - Diuretic use - CKD (glomerular disease may have FeNa >2% despite prerenal physiology) - Early sepsis (preserved tubular function)
Use FeUrea if diuretics given; measure both.
Clinical clues: Orthostatic hypotension, low JVP, dry mucous membranes, prerenal disease history (cirrhosis, CHF)
Intrinsic AKI (~40% of AKI)
Direct kidney injury: tubule necrosis, glomerulonephritis, interstitial nephritis, vascular injury.
Subcategories: 1. Acute Tubular Necrosis (ATN) — 45–50% of intrinsic - Ischemic (shock, sepsis, major surgery) - Nephrotoxic (aminoglycosides, cisplatin, myoglobin, hemoglobin, contrast) - See: ATN Deep Dive
- Acute Interstitial Nephritis (AIN) — 10–15% of intrinsic
- Drug-induced (most common), infection, autoimmune
- See: AIN Clinical Review
- Glomerulonephritis/Vasculitis — 5–10% of intrinsic
- Post-infectious, ANCA, SLE, anti-GBM
- Rhabdomyolysis / Hemolysis — 1–2% of intrinsic
- myoglobin/hemoglobin cast formation
Biomarkers: - FeNa > 2–3% (tubular damage → sodium wasting) - Urine casts (granular, RBC, WBC, muddy brown) - Urine dipstick positive for blood but RBC negative → myoglobin or hemoglobin - Urine osmolality < 400 mOsm/L (tubules cannot concentrate)
Postrenal AKI (~5% of AKI)
Urinary tract obstruction distal to kidney.
Common causes: - BPH (most common in elderly males) - Urinary retention (neurogenic, spinal cord injury) - Stones (bilateral or solitary kidney) - Malignancy (bladder, prostate, retroperitoneal) - Blood clots (post-TURP, tumor lysis)
Diagnosis: - Ultrasound/CT: Dilated collecting system, hydronephrosis - Postvoid residual > 100 mL suggests urinary retention - Relief of obstruction → rapid Cr improvement (within hours to 1–2 days)
Postobstructive diuresis: After relief, patient may diurese aggressively with loss of Na, K, PO4 — monitor and replace carefully.
KDIGO 2026: Temporal Definitions & Course
Transient vs Persistent AKI
| Category | Definition | Clinical Significance |
|---|---|---|
| Transient AKI | AKI criteria met for ≤48 hours then resolves | Often prerenal/functional; generally better prognosis |
| Persistent AKI | AKI criteria met for >48 hours | Higher risk of CKD transition, complications, and mortality |
Recurrent AKI
A new AKI episode occurring after complete resolution of a prior episode. Recurrent AKI is an independent risk factor for CKD progression and carries cumulative nephron loss with each episode.
Acute Kidney Disease (AKD)
AKD bridges the gap between AKI and CKD: - Definition: Kidney damage or dysfunction (GFR <60 mL/min, kidney damage markers, or structural abnormalities) persisting for ≤3 months but not meeting CKD duration criteria - AKI that has not resolved by 7 days transitions to AKD - AKD that persists beyond 3 months meets the definition of CKD
Baseline Serum Creatinine: Hierarchical Selection (KDIGO 2026)
When baseline SCr is unknown, use this hierarchy: 1. Outpatient SCr within prior 365 days (most reliable, closest to steady state) 2. Admission SCr (if no prior values available) 3. Lowest SCr during the current hospitalization (if no other values) 4. Back-calculated from CKD-EPI at eGFR 75 mL/min/1.73 m² (last resort imputation)
Clinical Pearl: The back-calculation approach (eGFR 75) overestimates baseline in patients with pre-existing CKD and underestimates it in young healthy patients. Always prefer a measured value when available.
AKI/AKD Resolution Criteria
| Resolution Category | AKI (within 7 days) | AKD (within 3 months) |
|---|---|---|
| Complete resolution | SCr returns to <1.2× baseline | SCr returns to <1.2× baseline |
| Partial resolution | SCr falls to 1.2–1.5× baseline | SCr falls to 1.2–1.5× baseline |
| No resolution | SCr remains >1.5× baseline → transitions to AKD | SCr remains >1.5× baseline → meets CKD criteria at 3 months |
Urine Biomarkers in AKI Differential
Urine Sediment Gold Standards
| Finding | Mechanism | Stage |
|---|---|---|
| Muddy brown casts | Hemoglobin or myoglobin-laden tubular casts | Intrinsic (ATN) |
| Granular casts | Desquamated tubule epithelium | Intrinsic |
| RBC casts + dysmorphic RBCs | Glomerulonephritis | Glomerular intrinsic |
| WBC casts + leukocytes | Interstitial nephritis or infection | AIN |
| Crystal casts | Crystal-induced AKI (uric acid, calcium oxalate, acyclovir) | Intrinsic/Toxic |
| Normal or hyaline casts only | Prerenal or postrenal | Prerenal/Postrenal |
Serum Biomarkers (Emerging)
- Neutrophil gelatinase-associated lipocalin (NGAL) — peaks 2–4h post-injury
- Tissue inhibitor of metalloproteinases (TIMP2) · Insulin-like growth factor binding protein 7 (IGFBP7) — TIMP2•IGFBP7 risk calculator for Stage 3 AKI
- Creatinine kinase (CK) — myoglobinuria (CK >5,000)
- Myoglobin — darker urine, dipstick+/RBC−, precipitation risk at pH <5.6 and low urine output
- Hemoglobin, LDH, indirect bilirubin — hemolysis markers
Clinical Pearl (KDIGO 2026 Update): NGAL and TIMP-2·IGFBP7 are now guideline-recommended biomarkers (Rec 2.4.1, 2B) and form the B axis of the three-axis staging system. In high-risk settings (cardiac surgery, ICU, sepsis), they should be considered alongside urine sediment + electrolytes + clinical assessment.
AKI → CKD Transition: Critical Window
30% of AKI Stage 3 patients develop CKD or ESRD despite apparent recovery of Cr to baseline.
Mechanism of CKD risk post-AKI: - Loss of functional nephron mass despite Cr normalization - Maladaptive repair: fibrosis, glomerulosclerosis - Glomerular hyperfiltration in remnant nephrons → progressive GFR loss - Persistent inflammation, oxidative stress
Mitigating strategies: 1. Early recognition & intervention — prevent progression to Stage 3 2. Avoid nephrotoxins during recovery — NSAIDs, ACE-I withdrawal, volume swings 3. Tight BP control — especially if baseline CKD or diabetes 4. Follow-up serum Cr at 3, 6, 12 months — if any elevation, refer to nephrology 5. Minimize ICU duration — multiorgan failure amplifies CKD risk
Clinical Decision Tree: AKI Workup
AKI Identified (↑Cr or ↓UO)
│
├─ HISTORY & EXAM FIRST
│ ├─ Volume status (JVP, skin turgor, orthostatics)
│ ├─ Medications (ACE-I, NSAIDs, diuretics, aminoglycosides)
│ ├─ Recent contrast, rhabdo symptoms, hemolysis signs
│ └─ Dysuria, flank pain (obstruction)
│
├─ LABS: Urine osmolality, FeNa, FeUrea, casts, dip
│
├─ IMAGING: Renal ultrasound (hydronephrosis?, size, echogenicity)
│
└─ CLASSIFY:
├─ FeNa <1% + exam findings → PRERENAL → fluid challenge
├─ FeNa >2% + casts → INTRINSIC → identify cause (ATN? AIN? GN?)
└─ Dilated system on US → POSTRENAL → urology consultBoard-Style Questions to Self-Test
- 50-year-old with Cr 0.8 → 1.6 (×2 rise) in 24h; UO 0.3 mL/kg/h; FeNa 0.5%; BUN:Cr 28:1
- Most likely: Prerenal AKI → tx volume
- 72-year-old post-cardiac surgery; muddy brown casts; FeNa 4%
- Most likely: ATN (ischemic) → supportive care
- Cr ↑ to Stage 3 after clarithromycin course; rash, eosinophilia, pyuria; urine eosinophils + WBC cast
- Most likely: AIN → steroids + d/c drug
- BPH patient, Cr 2.4, U/S shows bilateral hydronephrosis
- Postrenal AKI → Foley or urology → postobstructive diuresis risk
Version 2.0 | PA/Medical student level | Updated 2026-03-29 for KDIGO 2026 AKI/AKD Guideline