Gilteritinib

Gilteritinib's renal threats are syndrome-driven. (1) Differentiation syndrome: rapid myeloblast differentiation releases inflammatory cytokines, producing fever, capillary-leak edema, pleural/pericardial effusions, hypotension and acute kidney injury (a mix of prerenal hypoperfusion and intrarenal inflammatory injury). (2) Tumor lysis syndrome: cytoreduction releases uric acid, phosphate and potassium, causing urate and calcium-phosphate crystal nephropathy with intratubular obstruction and ATN. (3) Posterior reversible encephalopathy syndrome (PRES), a labeled risk, reflects endothelial dysfunction/hypertension. Volume shifts in differentiation syndrome can be both prerenal (capillary leak) and overload.

Differentiation syndrome: dyspnea, fever, weight gain/edema, effusions, hypotension and rising creatinine days-to-weeks after starting. TLS: hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia and AKI early in treatment. PRES: headache, seizures, visual change and hypertension with characteristic MRI findings.

Differentiation syndrome from a few days up to ~3 months (often within the first month); TLS early; PRES variable.

Oral selective inhibitor of FLT3 (including ITD and TKD/D835 mutations) and AXL. By blocking constitutively active FLT3 signaling it induces remission in relapsed/refractory FLT3-mutated AML — and, by relieving the maturation block, drives myeloblast differentiation.

For differentiation syndrome: start corticosteroids (e.g. dexamethasone 10 mg q12h), give diuretics for fluid overload, and interrupt gilteritinib if severe; support kidney function. For TLS: aggressive IV hydration, rasburicase for hyperuricemia, correct electrolytes, and dialyze for refractory metabolic derangement. For PRES: control blood pressure, treat seizures and hold the drug; it is typically reversible.