Clinical Case Scenario

A 65-year-old man, 7 months after allogeneic HSCT, develops chronic GVHD treated with steroids and sirolimus. He presents with resistant hypertension, edema, oliguria, proteinuria, and worsening kidney function (Cr 2.95 mg/dL).

Peripheral smear shows no significant schistocytosis. LDH, haptoglobin, and ADAMTS13 are normal.

Kidney biopsy reveals endothelial injury, glomerular thrombi, GBM double contours, and arteriolar mucoid intimal edema. Immunofluorescence is negative.

Fig:  Segmental thrombi with capillary wall thickening.

Wrong Answer: ❌ A. Plasma Exchange (PLEX)
PLEX is highly effective in TTP (severe ADAMTS13 deficiency) but has inconsistent benefit in transplant-associated TMA, which is primarily driven by endothelial injury and complement activation.

Wrong Answer: ❌ B. High-Dose Corticosteroids
Steroids may help control underlying GVHD but do not directly treat complement-mediated TA-TMA and are not considered definitive therapy.

Right Answer: ✅ C. Eculizumab

Key Learning Point

Transplant-associated renal thrombotic microangiopathy (TA-TMA) can present as isolated renal disease without systemic hemolysis. In a post-HSCT patient with hypertension, proteinuria, AKI, and characteristic renal biopsy findings, complement-mediated TA-TMA should be suspected. Early withdrawal of the offending agent and complement blockade with eculizumab can be kidney-saving and potentially life-saving.

CLINICAL PEARLS

💎 Normal LDH, haptoglobin, and absence of schistocytes do not exclude TA-TMA—sometimes the kidney is the only organ telling the story.
🎯 TTP → Think PLEX
🎯 Complement-mediated TA-TMA → Think Eculizumab
🎯 Drug-induced TMA → Stop the offending agent first

Wrong Answer: ❌ D. Restart Sirolimus at a Lower Dose
Sirolimus is a recognized trigger of endothelial injury and TMA; re-exposure may worsen renal damage rather than improve outcomes.

Wrong Answer: ❌ E. Cyclophosphamide
Cyclophosphamide has no established role in the treatment of drug-induced or transplant-associated TMA and does not target the underlying pathogenic mechanism.