Vorasidenib

Vorasidenib has no established intrinsic tubular, glomerular, or vascular nephrotoxic mechanism. Any rise in serum creatinine is best understood as a pseudo-AKI: IDH inhibitors of this class (e.g., ivosidenib) inhibit organic cation transporter 2 (OCT2) and multidrug and toxin extrusion (MATE) proteins on the proximal tubule, blocking tubular secretion of creatinine. This elevates measured serum creatinine and lowers the creatinine-based estimated GFR without a true decline in glomerular filtration. Beyond this, kidney involvement is largely prerenal/hemodynamic and uncommon.

Typically asymptomatic. The most likely renal-laboratory finding is a modest, stable rise in serum creatinine without oliguria, electrolyte derangement, proteinuria, hematuria, or active urinary sediment. True AKI, interstitial nephritis, or electrolyte wasting are not characteristic. The dominant on-treatment toxicities are hepatic (transaminase elevation) and neurologic, not renal.

For an isolated creatinine rise without other signs of kidney injury, recognize pseudo-AKI: confirm with a cystatin C-based eGFR or by checking that urinalysis and electrolytes are bland, and avoid unnecessary drug interruption. Manage true AKI, if it arises, by the usual approach — assess volume status, review the medication list, and exclude obstruction and other causes.Lesion-level management framework

No dedicated renal-impairment dose adjustment is established for mild-to-moderate impairment; vorasidenib is hepatically metabolized (CYP1A2/CYP3A) and dose modifications in the label are driven by hepatotoxicity, not renal function. Data at CrCl ≤40 mL/min and on dialysis are lacking; there the label directs monitoring for increased adverse reactions and modifying the dose accordingly. A creatinine-based eGFR fall from blocked tubular secretion should not by itself trigger renal dose reduction.

Not characterized. Vorasidenib is a small molecule but is highly protein-bound and extensively hepatically cleared, so it is unlikely to be meaningfully removed by hemodialysis; no formal dialysis data exist.

Distinguish a benign transporter-mediated creatinine rise (pseudo-AKI: stable creatinine, normal cystatin C-based GFR, bland sediment, no electrolyte wasting) from true intrinsic AKI. Consider prerenal azotemia from volume depletion, concomitant nephrotoxins, contrast or other glioma-directed therapies, and — given frequent corticosteroid and anticonvulsant co-medication in glioma patients — drug-related interstitial nephritis from those agents rather than from vorasidenib itself.