4.4 Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), & Nephrology
Key Takeaways
- KDIGO criteria define AKI by a serum creatinine increase ≥ 26.5 µmol/L in 48h, a creatinine increase ≥ 1.5x baseline within 7 days, or urine output < 0.5 mL/kg/h for 6 hours.
- Prerenal AKI features FENa < 1% (FeUrea < 35% on diuretics), urine Na < 20 mmol/L, and hyaline casts; Intrinsic ATN features FENa > 2%, urine Na > 40 mmol/L, and muddy brown granular casts.
- Nephrotic syndrome presents with heavy proteinuria (> 3.5 g/day or UACR > 220 mg/mmol), hypoalbuminemia (< 30 g/L), edema, and hyperlipidemia; Nephritic syndrome presents with dysmorphic RBCs, RBC casts, hypertension, oliguria, and mild-moderate proteinuria.
- CKD management focuses on delaying progression using ACE inhibitors or ARBs for proteinuria (UACR > 3.0 mg/mmol) and SGLT2 inhibitors (empagliflozin, dapagliflozin) for eGFR ≥ 20 mL/min/1.73m² regardless of diabetes status.
- Urgent hemodialysis indications follow the AEIOU mnemonic: Acidosis (pH < 7.10), Electrolytes (refractory K+ > 6.5 mmol/L), Intoxications (SLIME), Overload (refractory pulmonary edema), Uremia (encephalopathy, pericarditis, bleeding).
4.4 Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), & Nephrology
KDIGO Staging & Etiology Differentiation of AKI
According to KDIGO (Kidney Disease: Improving Global Outcomes) guidelines, Acute Kidney Injury (AKI) is defined by meeting any of the following:
- Increase in serum creatinine by ≥ 26.5 µmol/L within 48 hours.
- Increase in serum creatinine to ≥ 1.5 times baseline within 7 days.
- Urine volume < 0.5 mL/kg/h for 6 consecutive hours.
KDIGO AKI Staging Grid
| Stage | Serum Creatinine Threshold | Urine Output Threshold |
|---|---|---|
| Stage 1 | 1.5 – 1.9x baseline OR increase ≥ 26.5 µmol/L | < 0.5 mL/kg/h for 6 – 12 hours |
| Stage 2 | 2.0 – 2.9x baseline | < 0.5 mL/kg/h for ≥ 12 hours |
| Stage 3 | 3.0x baseline OR creatinine ≥ 353.6 µmol/L OR initiation of RRT | < 0.3 mL/kg/h for ≥ 24 hours OR Anuria for ≥ 12 hours |
Etiological Classification & Diagnostic Indices
| Feature | Prerenal AKI | Intrinsic AKI (ATN) | Intrinsic AKI (AIN) | Postrenal AKI |
|---|---|---|---|---|
| Primary Cause | Hypovolemia, HF, Sepsis, ACEi/ARB + NSAIDs | Ischemia, Contrast, Aminoglycosides, Rhabdomyolysis | Drug hypersensitivity (PPIs, NSAIDs, Penicillins) | BPH, Prostate Cancer, Bilateral Calculi, Neurogenic Bladder |
| BUN:Cr Ratio | > 80:1 (mmol:mmol) | < 40:1 | < 40:1 | Variable |
| FENa (%) | < 1% (FeUrea < 35%) | > 2% | > 1% | Variable |
| Urine Sodium | < 20 mmol/L | > 40 mmol/L | > 20 mmol/L | Variable |
| Urine Osmolality | > 500 mOsm/kg | < 350 mOsm/kg | Variable | < 350 mOsm/kg |
| Urinalysis / Casts | Hyaline casts | Muddy brown granular casts | WBC casts, Eosinophiluria | Normal / RBCs / Pyuria |
| Renal Ultrasound | Normal | Normal | Normal / Enlarged | Hydronephrosis / Hydroureter |
Formula for Fractional Excretion of Sodium (FENa): FENa (%) = [(Urine Na x Serum Cr) / (Serum Na x Urine Cr)] x 100. In patients taking loop diuretics, FeUrea (< 35%) is more accurate than FENa.
Glomerular Diseases: Nephrotic vs Nephritic Syndromes
Nephrotic vs Nephritic Syndrome Comparison
| Diagnostic Parameter | Nephrotic Syndrome | Nephritic Syndrome |
|---|---|---|
| Primary Pathology | Podocyte damage -> breakdown of filtration barrier | Glomerular inflammation -> cell proliferation & capillary damage |
| Clinical Triad | Anasarca, Heavy Proteinuria, Hypoalbuminemia | Hematuria, Oliguria, Hypertension |
| Proteinuria Level | > 3.5 g/24h (UACR > 220 mg/mmol) | Mild to Moderate (< 3.5 g/24h) |
| Serum Albumin | Hypoalbuminemia (< 30 g/L) | Normal or mildly decreased |
| Urine Sediment | Oval fat bodies, fatty casts, "Maltese cross" | Dysmorphic RBCs, RBC Casts |
| Major Complications | Hypercoagulability (loss of antithrombin III -> RVT/DVT), Hyperlipidemia | AKI, Hypertensive Emergency, Fluid Overload |
Key Glomerular Etiologies
- Minimal Change Disease: Most common cause of nephrotic syndrome in children. Normal glomeruli on light microscopy; podocyte effacement on electron microscopy. Highly responsive to corticosteroids (prednisone).
- Membranous Nephropathy: Most common primary nephrotic syndrome in Caucasian adults. Associated with anti-PLA2R antibodies, HBV, solid tumors, and NSAIDs. Thickened basement membrane with "spike and dome" pattern on silver stain.
- Diabetic Nephropathy: Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules), mesangial expansion, and progressive albuminuria.
- Post-Streptococcal GN (PSGN): Nephritic syndrome presenting 1–3 WEEKS AFTER group A beta-hemolytic streptococcal pharyngitis or impetigo. Characterized by LOW serum C3 complement and lumpy-bumpy subepithelial deposits.
- IgA Nephropathy (Berger Disease): Most common primary GN worldwide. Young adult presenting 1–2 DAYS AFTER an upper respiratory infection (synpharyngitic hematuria). Characterized by NORMAL serum C3 complement and mesangial IgA deposition.
- ANCA Vasculitis (GPA / Wegener): PR3-ANCA / c-ANCA positive. Triad of upper respiratory sinus lesions, lower respiratory pulmonary nodules/hemoptysis, and pauci-immune crescentic GN.
- Anti-GBM (Goodpasture) Disease: Autoantibodies against alpha-3 chain of type IV collagen causing pulmonary hemorrhage PLUS Rapidly Progressive GN. Linear IgG deposition along glomerular basement membrane.
Chronic Kidney Disease (CKD) Staging & Progression Delay
CKD is defined by kidney damage or eGFR < 60 mL/min/1.73m² present for > 3 months.
KDIGO Staging Matrix
- eGFR Categories: G1 (≥ 90), G2 (60–89), G3a (45–59), G3b (30–44), G4 (15–29), G5 (< 15 or Dialysis).
- Albuminuria Categories: A1 (UACR < 3.0 mg/mmol - Normal/Mild), A2 (UACR 3.0–30.0 mg/mmol - Moderate), A3 (UACR > 30.0 mg/mmol - Severe).
Evidence-Based Interventions to Slow CKD Progression
- RAAS Blockade (ACEi or ARB): Titrated to maximum tolerated dose in all patients with CKD and hypertension or albuminuria (UACR > 3.0 mg/mmol). Reduces intraglomerular pressure by dilating efferent arterioles. Expect up to a 30% rise in serum creatinine upon initiation; do NOT discontinue unless creatinine rises > 30% or refractory hyperkalemia develops.
- SGLT2 Inhibitors (Empagliflozin, Dapagliflozin): Indicated for all CKD patients with eGFR ≥ 20 mL/min/1.73m² and UACR > 3.0 mg/mmol, regardless of diabetes status. Reduces hyperfiltration, slows eGFR decline, and reduces ESKD/death.
- Blood Pressure Control: Target BP < 120/80 mmHg per KDIGO 2021 guidelines using standardized measurement.
- Lifestyle Modifications: Dietary sodium restriction (< 2.0 g/day), protein intake 0.8 g/kg/day, avoidance of nephrotoxins (NSAIDs, IV contrast).
Indications for Urgent Hemodialysis (AEIOU Mnemonic)
| Letter | Emergency Indication | Clinical Diagnostic Threshold |
|---|---|---|
| A | Acidosis | Severe refractory metabolic acidosis with pH < 7.10 despite medical management |
| E | Electrolytes | Severe refractory hyperkalemia with K+ > 6.5 mmol/L or ECG changes persistent despite therapy |
| I | Intoxications | Poisoning with dialyzable toxins (SLIME: Salicylates, Lithium, Isopropanol, Methanol, Ethylene glycol) |
| O | Overload | Refractory volume overload / Acute pulmonary edema non-responsive to high-dose IV loop diuretics |
| U | Uremia | Symptomatic uremia: Uremic Pericarditis, uremic encephalopathy/asterixis, uremic bleeding |
[!IMPORTANT] MCCQE1 High-Yield Distinction: IgA Nephropathy vs Post-Streptococcal GN • IgA Nephropathy (Berger Disease): Recurrent gross hematuria occurring CONCURRENTLY (1–2 days after) an upper respiratory tract infection. Serum C3 complement levels are NORMAL. • Post-Streptococcal GN: Hematuria occurring 1–3 WEEKS AFTER a streptococcal pharyngeal or skin infection. Serum C3 complement levels are LOW (hypocomplementemia).
A 68-year-old male with a history of hypertension and osteoarthritis presents with weakness and oliguria 4 days after undergoing a contrast-enhanced CT angiogram. Current medications include Ramipril and Naproxen. Labs show BUN 32 mmol/L and Creatinine 340 µmol/L (baseline 90 µmol/L). Urinalysis demonstrates urine Na 58 mmol/L, FENa 2.6%, and dark muddy brown granular casts on microscopy. What is the primary diagnosis?
A 19-year-old university student presents with dark, tea-colored urine that began yesterday alongside a sore throat and fever. Blood pressure is 138/86 mmHg. Physical exam reveals mild pharyngeal erythema but no edema. Labs: Creatinine 115 µmol/L, Serum C3 complement level 1.1 g/L (Normal 0.9–1.8 g/L), and Serum C4 level normal. Urinalysis reveals 3+ blood, dysmorphic RBCs, and 1+ protein. What is the most likely diagnosis?
A 62-year-old female with ESKD missing hemodialysis for 5 days presents to the ED confused and dyspneic. Vitals: BP 178/104 mmHg, HR 110/min, RR 26/min, SpO2 86% on room air. Physical exam demonstrates bilateral lung crackles, elevated JVP, and a pericardial friction rub. Labs show K+ 6.8 mmol/L with peaked T waves on ECG, arterial pH 7.08, and BUN 42 mmol/L. In addition to medical hyperkalemia management, what emergency intervention is indicated?