Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Antibody-drug conjugate (Trop-2/SN-38)
Sacituzumab govitecan
Trodelvy · SG
A Trop-2/SN-38 conjugate whose diarrhea can drive prerenal AKI — with a rare biopsy-proven interstitial nephritis signal.
ModerateAntibody-drug conjugate · approved 2020
Triple-negative breast cancerHR+/HER2- breast cancerUrothelial carcinoma
Signature kidney injury
Prerenal / Hemodynamic AKI
AKI is mainly prerenal, driven by the severe diarrhea/nausea and neutropenia that dominate the ASCENT safety profile; renal-specific incidence is not well quantified. A biopsy-proven severe acute tubulointerstitial nephritis requiring hemodialysis has also been reported (case-level).
Source: Guarin et al., BMC Nephrol 2024 (case); Bardia et al., N Engl J Med 2021 (ASCENT)
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityModerate
ReversibilityVariable
Evidence0 refs
Nephron map
Vasculature / EndotheliumGlomerular & peritubular capillaries
Proximal Tubule
Distal Tubule / Collecting Duct
Interstitium
Prerenal / Hemodynamic AKI
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Mechanism of kidney injury
Predominantly hemodynamic: GI toxicity (diarrhea, vomiting) causes volume depletion and prerenal AKI, which can progress to ischemic ATN. SN-38 toxicity (and thus diarrhea/neutropenia severity) is amplified in UGT1A1 poor metabolizers, e.g. UGT1A1*28 homozygotes. Trop-2 is expressed in collecting ducts and, to a lesser extent, proximal tubule; a rare immune-mediated acute tubulointerstitial nephritis has been described on biopsy, expanding the renal differential beyond pure prerenal physiology.
Clinical presentation
AKI in the setting of diarrhea/dehydration with bland sediment; in the reported AIN case, severe AKI with nephrotic-range proteinuria requiring dialysis, responsive to corticosteroids and renal replacement therapy. Watch for concurrent grade 3-4 neutropenia.
Onset
Variable; prerenal AKI tracks with GI toxicity during treatment cycles.
Reversibility
Variable
Anticancer mechanism
Antibody-drug conjugate targeting Trop-2 and delivering SN-38, the active topoisomerase I-inhibitor metabolite of irinotecan, via a hydrolyzable linker with a high drug-to-antibody ratio. Approved for metastatic triple-negative and HR+/HER2- breast cancer and urothelial carcinoma.
Management
Rehydrate, manage diarrhea and neutropenia, and hold drug for significant AKI; for steroid-responsive features or AKI out of proportion to volume status, pursue kidney biopsy and consider corticosteroids for biopsy-proven AIN, with supportive care/dialysis as needed.
Risk factors
- Severe diarrhea/vomiting and dehydration
- UGT1A1*28 homozygosity (reduced SN-38 glucuronidation)
- Pre-existing CKD
- Concurrent nephrotoxins
Prevention
- Aggressive antidiarrheal management (loperamide) and hydration
- Consider UGT1A1 genotype in patients with severe early toxicity
- Monitor renal function, volume status and CBC each cycle
Note · Direct nephrotoxicity (interstitial nephritis) is rare and case-level; the dominant renal risk is prerenal from GI toxicity.
Clinical depth
Renal dose adjustment
No established renal dose adjustment; pivotal trials did not define renal cutoffs and the active SN-38 is hepatically glucuronidated (UGT1A1), not renally cleared. Use clinical judgment in advanced CKD/ESKD given limited data.
Dialyzability & ESKD dosing
The intact ADC and protein-bound SN-38 are not appreciably dialyzed; HD in reported cases was for AKI support, not drug removal.
Differential diagnosis
Distinguish prerenal/ischemic ATN from diarrhea (fluid-responsive, bland sediment, FeNa low then rising) from drug-induced AIN (AKI out of proportion to volume loss, possible eosinophiluria/sterile pyuria, steroid-responsive on biopsy). UGT1A1*28 status helps explain unusually severe GI toxicity.
Monitoring
- Serum creatinine and volume status each cycle, especially during diarrhea
- CBC for neutropenia (a marker of SN-38 exposure/UGT1A1 status)
- Urinalysis/urine protein if AKI is disproportionate to volume status (AIN screen)
Key trials & series
- ASCENT (Bardia NEJM 2021, metastatic TNBC)
- Guarin BMC Nephrol 2024 (biopsy-proven AIN requiring HD)
Clinical pearls
- The everyday renal risk is dehydration from diarrhea — but remember the rare biopsy-proven AIN if AKI does not track with volume status.
- UGT1A1*28 homozygotes get more SN-38, more diarrhea/neutropenia, and therefore more prerenal AKI risk.
- Trop-2 is expressed in the collecting duct, providing a plausible substrate for the reported interstitial injury.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIAcute Interstitial NephritisAcute Tubular Necrosis
Beyond the kidney
Class-level context for the major non-renal toxicities of antibody-drug conjugate (trop-2/sn-38)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.
LandmarkSacituzumab-govitecan-induced severe acute tubulointerstitial nephritis requiring hemodialysis.Guarin G et al. · BMC Nephrol 2024 · PMID 39522022Biopsy-proven acute tubulointerstitial nephritis; discusses Trop-2 expression and UGT1A1*28 risk.PMIDSacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.Bardia A et al. · N Engl J Med 2021 · PMID 33882206ASCENT phase III defining the diarrhea/neutropenia-dominant safety profile that drives prerenal AKI.PMIDAntibody-Drug Conjugates: The Toxicities and Adverse Effects That Emergency Physicians Must Know.Markides DM et al. · Ann Emerg Med 2024 · PMID 39641680Class review noting diarrhea/dehydration and acute toxicities of ADCs including sacituzumab govitecan.PMIDAnticancer Drug-Induced Acute Kidney Injury.Izzedine H et al. · Kidney Int Rep 2017 · PMID 29318217Onconephrology reference covering prerenal and interstitial mechanisms of drug-induced AKI.
Related agents
Other agents sharing the same signature kidney injury.