A 47-year-old cystic fibrosis patient, 1 week post–lung transplant, develops worsening creatinine (2.5 mg/dL from baseline 0.8mg/dl). He received 200 g IV mannitol intra-operatively for cerebral oedema prophylaxis in view of large volume resuscitation during intraoperative period. He also underwent CT pulmonary angiography 72 hours back to rule out pulmonary embolism for persistent hypoxemia.

Immunosuppression: tacrolimus (trough 9ng/ml), azathioprine, prednisone.

Urine output: 3 L/day.

Labs:

• Serum Na: 155 mEq/L
• Serum Osm: 330 mOsm/kg
• Urine Osm: 280 mOsm/kg
• Urine Na: 20 mEq/L
• FeNa: 1.5%
• Urine microscopy: tubular epithelial cells with cytoplasmic vacuolization
• Serum glucose: 110 mg/dL

Wrong Answer: A. Hyperacute tacrolimus nephrotoxicity

Wrong Answer: B. Contrast-induced nephropathy (received contrast 72h ago for PE)

Right Answer: C. Mannitol-induced osmotic tubulopathy

High-Yield Rationale:

• Massive mannitol load → filtered but poorly reabsorbed → accumulates in proximal tubular cells.
• Causes osmotic swelling + cytoplasmic vacuolization = osmotic nephrosis.
• Polyuria (osmotic diuresis) instead of expected oligo-anuric ATN.
• High serum osmolality + hypernatremia from mannitol-induced free water loss.
• FeNa >1% → intrinsic tubular injury pattern.
• Contrast AKI: typically FeNa <1% + muddy brown casts.
• Tacrolimus toxicity: usually vasoconstriction, not polyuria.
• aHUS: would show MAHA + thrombocytopenia.

Clinical Pearls

1. Polyuric AKI = Think Osmotic Load
A rising creatinine with high urine output is a red flag for osmotic nephrosis rather than ATN. (Mannitol, IVIG with sucrose, hydroxyethyl starch, radiocontrast, etc.)

2. “Osmolality Mismatch” is Diagnostic
Serum Osm >> Urine Osm suggests the kidney is “leaking” water due to retained osmoles → hallmark of mannitol injury.

3. Vacuolated Tubules = Pathognomonic Clue
Cytoplasmic vacuolization on urine microscopy is one of the few “near-pathognomonic” findings in nephrocritical care—don’t miss it.

4. Tacrolimus Toxicity Can Occur at Therapeutic Levels
Therapeutic troughs (like 9 ng/mL here) do not exclude CNI vasoconstriction or TMA. Clinical context beats the number.

5. Osmotic Nephrosis vs. ATN: Opposites

Management Insight

• Stop mannitol immediately
• Correct hypernatremia slowly
• Supportive care; no role for diuretics
• Consider biopsy only if unclear or prolonged AKI (more common in transplant patients)

Teaching Box

✔ Mannitol AKI = polyuria + hypernatremia + low urine osm + vacuoles

✔ Differentiates from contrast AKI (oliguria + muddy casts)

✔ Differentiates from tacrolimus toxicity (hypertension, vasoconstriction, TMA)

Wrong Answer: D. Late-onset atypical Haemolytic Uremic Syndrome(aHUS)