Decitabine

Rapid cytoreduction of responsive marrow releases uric acid, phosphate and potassium; intratubular uric-acid and calcium-phosphate precipitation, combined with volume depletion, produces obstructive/crystal-related and prerenal-ischemic AKI (tumor lysis nephropathy). Separately, rare biopsy-proven decitabine-associated thrombotic microangiopathy reflects endothelial injury with glomerular fibrin thrombi, crescents and tubular necrosis.

Hyperuricemia, hyperphosphatemia, hyperkalemia and a rising creatinine within days of a responding cycle in tumor lysis; in the rare TMA presentation, nephrotic-range proteinuria, hematuria, schistocytes/thrombocytopenia and AKI develop over weeks.

Early after a treatment cycle (days) for tumor lysis; TMA over weeks.

Deoxycytidine analog phosphorylated to its triphosphate and incorporated directly into DNA, where it forms an irreversible covalent complex with DNA methyltransferase, causing enzyme depletion, genome-wide hypomethylation and reactivation of silenced tumor-suppressor genes; at higher concentrations it is also directly cytotoxic. Used for myelodysplastic syndromes and acute myeloid leukemia.

Treat tumor lysis with aggressive hydration, rasburicase (preferred when urate is high or the patient is at high risk) or allopurinol, and correction of hyperkalemia/hyperphosphatemia; hold the drug and provide supportive care for AKI, with hemodialysis for refractory metabolic derangements. For suspected TMA, discontinue decitabine; reported cases recovered after withdrawal with supportive care (plasma exchange is generally not effective for drug-induced TMA).