# AKI Staging & Classification: KDIGO Framework

Updated March 2026 to reflect KDIGO 2026 draft Clinical Practice Guideline for AKI and AKD

## KDIGO 2026 draft Three-Axis Staging System (C/U/B)

Key Point

The KDIGO 2026 draft proposes replacing 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 serum creatinine ≥4.0 mg/dL (absolute value, not a 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

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## 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)

Clinical Pearl

**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)

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### **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

1.  **Acute Interstitial Nephritis (AIN)** — 10–15% of intrinsic
    - Drug-induced (most common), infection, autoimmune
    - See: AIN Clinical Review
2.  **Glomerulonephritis/Vasculitis** — 5–10% of intrinsic
    - Post-infectious, ANCA, SLE, anti-GBM
3.  **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)

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### **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)

Clinical Warning

**Postobstructive diuresis:** After relief, patient may diurese aggressively with loss of Na, K, PO4 — monitor and replace carefully.

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## KDIGO 2026 draft: 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 draft)

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

**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 |

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## 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

**Clinical Pearl (KDIGO 2026 draft 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.

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## AKI → CKD Transition: Critical Window

Clinical Warning

**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

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## 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 consult

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## Related Resources

- Detailed AKI Review
- Acute Tubular Necrosis
- Acute Interstitial Nephritis
- AKI Workup & Management Summary
- Prerenal AKI Deep Dive

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## Board-Style Questions to Self-Test

1.  **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
2.  **72-year-old post-cardiac surgery; muddy brown casts; FeNa 4%**
    - Most likely: ATN (ischemic) → supportive care
3.  **Cr ↑ to Stage 3 after clarithromycin course; rash, eosinophilia, pyuria; urine eosinophils + WBC cast**
    - Most likely: AIN → steroids + d/c drug
4.  **BPH patient, Cr 2.4, U/S shows bilateral hydronephrosis**
    - Postrenal AKI → Foley or urology → postobstructive diuresis risk

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*Version 2.0 \| PA/Medical student level \| Updated 2026-03-29 for KDIGO 2026 draft AKI/AKD Guideline*


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