Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Antibody-drug conjugate (FRα/DM4)
Mirvetuximab soravtansine
Elahere · MIRV
An FRα/DM4 conjugate for ovarian cancer — ocular and GI toxicity dominate; renal data are emerging.
MildAntibody-drug conjugate · approved 2022
Ovarian cancerFallopian tube cancerPrimary peritoneal cancer
Signature kidney injury
Prerenal / Hemodynamic AKI
Direct nephrotoxicity is not a prominent trial signal; ocular (keratopathy/blurred vision, ~50% any-grade across pooled trials) and GI/fatigue toxicities dominate. AKI is case-level and chiefly volume-mediated (GI toxicity). Renal-specific incidence is not quantified.
Source: Moore et al., N Engl J Med 2023 (MIRASOL)
Mechanism of kidney injury
Indirect/hemodynamic: nausea, vomiting and diarrhea cause volume depletion and prerenal AKI. A specific direct tubular mechanism is not established in humans; FRα is expressed in proximal tubule (the basis for folate-receptor tracer uptake by the kidney), but clinically meaningful tubular toxicity has not emerged at approved doses. The maytansinoid payload concentrates instead in corneal epithelium, producing the hallmark ocular toxicity.
Clinical presentation
AKI in the setting of GI toxicity/dehydration with bland sediment; renal function otherwise usually preserved. Ocular symptoms (blurred vision, keratopathy, dry eye) are the hallmark toxicity and are generally low-grade and reversible.
Onset
Variable; tracks with GI toxicity during treatment cycles.
Reversibility
Variable
Anticancer mechanism
Antibody-drug conjugate targeting folate receptor alpha (FRα) and delivering the maytansinoid microtubule inhibitor DM4 via a cleavable disulfide linker. Approved for FRα-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer.
Management
Rehydrate, manage GI toxicity, hold drug for significant AKI, supportive care; ocular toxicity is managed by ophthalmology-guided dose modification.
Risk factors
- GI toxicity and dehydration
- Pre-existing CKD
- Concurrent nephrotoxins
Prevention
- Manage nausea/diarrhea and maintain hydration
- Prophylactic ocular surface care (lubricating and corticosteroid eye drops) with baseline and periodic eye exams
- Monitor renal function and electrolytes each cycle
Note · Renal data are emerging; the defining toxicities are ocular and GI rather than renal.
Clinical depth
Renal dose adjustment
No renal dose adjustment defined for mild-moderate impairment; data are limited in severe impairment/ESKD. DM4 is hepatically metabolized rather than renally cleared.
Dialyzability & ESKD dosing
Not appreciably dialyzed (large ADC; protein-bound maytansinoid payload).
Differential diagnosis
AKI is prerenal from GI losses (volume-responsive, bland sediment) rather than tubular; the management-defining toxicity is ocular, paralleling belantamab mafodotin. True nephron injury would be unexpected and should prompt a search for alternative causes.
Monitoring
- Ophthalmologic exam at baseline, every other cycle for the first 8 cycles, and as indicated
- Serum creatinine, electrolytes and volume status each cycle (GI-loss-driven AKI)
Key trials & series
- MIRASOL (Moore NEJM 2023, phase III)
- SORAYA (Matulonis JCO 2023, registrational)
- Hendershot Gynecol Oncol Rep 2023 (pooled ocular safety, n=464)
Clinical pearls
- Mirvetuximab and belantamab share the ADC ocular signature - eye care and exams, not renal monitoring, define routine surveillance.
- FRα is expressed in the proximal tubule (hence renal tracer uptake), yet clinical tubular toxicity has not materialized - the kidney risk is hemodynamic.
- Most AKI is dehydration from GI toxicity and reverses with fluids.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of antibody-drug conjugate (frα/dm4)s.
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression (payload-dependent)
Ophthalmic
Keratopathy, uveitis, retinopathy
- Keratopathy (belantamab, mirvetuximab, tisotumab)
Pulmonary
Pneumonitis, ILD, effusions, hypertension
- Interstitial lung disease (deruxtecan ADCs)
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- Peripheral neuropathy (MMAE payloads)
Evidence
4 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkMirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer.Moore KN et al. · N Engl J Med 2023 · PMID 38055253MIRASOL phase III defining the ocular/GI-dominant safety profile.PMIDEfficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study.Matulonis UA et al. · J Clin Oncol 2023 · PMID 36716407Registrational SORAYA trial characterizing the toxicity profile.PMIDStrategies for prevention and management of ocular events occurring with mirvetuximab soravtansine.Hendershot A et al. · Gynecol Oncol Rep 2023 · PMID 37102083Pooled analysis of 464 patients: 50% ocular AEs (mostly grade <=2), with prevention/monitoring guidance - defines the dominant ocular toxicity.PMIDAntibody-Drug Conjugates: The Toxicities and Adverse Effects That Emergency Physicians Must Know.Markides DM et al. · Ann Emerg Med 2024 · PMID 39641680Class review of ADC toxicities including maytansinoid-payload agents.
Related agents
Other agents sharing the same signature kidney injury.