Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Antibody-drug conjugate (tissue factor/MMAE)
Tisotumab vedotin
Tivdak · TV
A tissue-factor MMAE ADC defined by ocular and bleeding toxicity — renal involvement is essentially unreported.
MildAntibody-drug conjugate (tissue factor/MMAE) · approved 2021
Recurrent or metastatic cervical cancer
Signature kidney injury
Prerenal / Hemodynamic AKI
Direct nephrotoxicity is not a recognized signal. In the pivotal innovaTV 301 and innovaTV 204 trials the defining toxicities were ocular (conjunctivitis, dry eye, keratitis), bleeding/epistaxis and peripheral neuropathy; a quantified renal-injury rate was not reported. Renal involvement, if any, is indirect/case-level.
Source: Vergote et al., N Engl J Med 2024 (innovaTV 301)
Mechanism of kidney injury
No characteristic intrinsic renal lesion is established. Tissue factor's role in coagulation underlies the bleeding toxicity rather than a renal one. Any renal injury is most plausibly indirect — prerenal/hemodynamic from volume depletion (GI toxicity) — while a theoretical MMAE-payload tubular concern is not supported by trial renal data. The large antibody is not renally cleared. Characterization is conservative given the absence of renal-specific literature.
Clinical presentation
If present, a prerenal creatinine rise during GI volume loss; there is no signature tubular or glomerular syndrome. The dominant clinical findings are ocular surface disease, epistaxis/bleeding and peripheral neuropathy.
Onset
Not characterized for renal events; any prerenal AKI would track volume depletion (days).
Reversibility
Reversible
Anticancer mechanism
Antibody-drug conjugate of an anti-tissue-factor IgG1 linked via a protease-cleavable linker to monomethyl auristatin E (MMAE). After binding tissue factor (overexpressed on cervical and other tumors) and internalization, MMAE is released to disrupt microtubules and induce apoptosis with bystander killing. Approved for recurrent or metastatic cervical cancer after prior therapy.
Management
Supportive: volume resuscitation for prerenal AKI, antiemetics, and drug-hold/dose modification per label for toxicity. Manage the dominant ocular and bleeding toxicities per protocol; there is no drug-specific renal therapy.
Risk factors
- Volume depletion from GI toxicity
- Pre-existing CKD
- Bleeding/coagulopathy (drug-specific) compounding hemodynamic instability
- Concurrent nephrotoxins
Prevention
- Mandatory ocular prophylaxis protocol (the priority toxicity)
- Hydration and antiemetics
- Routine creatinine monitoring
- Bleeding precautions
Note · Renal-specific literature is essentially absent — ocular toxicity, hemorrhage and neuropathy dominate. The prerenal characterization is conservative and mechanistic; incidence is not quantified.
Clinical depth
Renal dose adjustment
No renal dose adjustment is established; not studied in severe impairment/ESKD. Modify/hold for ocular, bleeding and other toxicities per label.
Dialyzability & ESKD dosing
The IgG–MMAE conjugate is not dialyzable; released MMAE is highly protein-bound and not meaningfully removed by dialysis. No ESKD dosing guidance exists.
Differential diagnosis
Prerenal AKI from GI volume loss (fluid-responsive) vs unrelated intrinsic renal disease; there is no characteristic tisotumab renal lesion, so significant AKI warrants a search for an alternative cause.
Monitoring
- Ophthalmologic examination at baseline and per protocol (the priority)
- Serum creatinine/eGFR periodically
- Bleeding/hemoglobin and volume status
Key trials & series
- innovaTV 301 (Vergote NEJM 2024) — pivotal phase 3
- innovaTV 204 (Coleman Lancet Oncol 2021) — registrational phase 2
- innovaTV 205 — combination study
Clinical pearls
- Eyes and bleeding, not kidneys: tisotumab's defining toxicities are ocular and hemorrhagic.
- Any AKI is most likely prerenal from volume loss — hydrate and give antiemetics.
- It is a large antibody conjugate — no renal dosing and no dialysis removal.
- Renal literature is absent; keep claims qualitative and conservative.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKI
Beyond the kidney
Class-level context for the major non-renal toxicities of antibody-drug conjugate (tissue factor/mmae)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.
LandmarkTisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer.Vergote I et al. · N Engl J Med 2024 · PMID 38959480Pivotal phase 3 innovaTV 301; full safety profile with ocular/bleeding/neuropathy dominance and no prominent renal signal.PMIDEfficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study.Coleman RL et al. · Lancet Oncol 2021 · PMID 33845034Registrational phase 2; detailed ocular-predominant adverse-event profile.PMIDTisotumab Vedotin Safety and Tolerability in Clinical Practice: Managing Adverse Events.Arn CR et al. · J Adv Pract Oncol 2023 · PMID 37009403Practical AE-management review confirming ocular/bleeding/neuropathy as the key signals.PMIDRenal Side Effects of Novel Molecular Targeted Oncologic Agents.Fenoglio R et al. · G Ital Nefrol 2023 · PMID 38007829Onconephrology class review providing renal context for ADC/targeted agents.
Related agents
Other agents sharing the same signature kidney injury.