Cisplatin
Platinol · Platinum agent
Proximal tubular ATN + magnesium wasting; the archetype.
ATNLYTEPRE
SevereOpen →
c-Met ADC (MMAE)
Telisotuzumab vedotin (Teliso-V)
Emrelis · c-Met ADC (MMAE)
c-Met-directed MMAE antibody-drug conjugate; renal risk is class-extrapolated from MMAE payload handling.
Moderatec-Met antibody-drug conjugate (MMAE) · approved 2025
Locally advanced or metastatic non-squamous EGFR wild-type non-small cell lung cancer with high c-Met protein overexpression, after at least one prior systemic therapy (accelerated approval)
Signature kidney injury
Acute Tubular Necrosis
Drug-specific renal toxicity data for telisotuzumab vedotin are sparse. In the pivotal LUMINOSITY trial the dominant toxicities were peripheral neuropathy, peripheral edema, hypoalbuminemia, fatigue, and nausea; clinically significant nephrotoxicity was not highlighted as a frequent or signature event. Any renal risk is therefore largely class-extrapolated from MMAE-bearing ADCs rather than measured for this agent. A precise renal incidence rate cannot be stated with confidence from existing literature.
Source: 38843488
Mechanism of kidney injury
Mechanistically, injury is inferred from the MMAE payload. After partial deconjugation or nonspecific uptake, free or antibody-bound MMAE can be handled by the proximal tubule, where the antimitotic payload may injure highly metabolically active tubular epithelium and produce acute tubular injury (ATN). Marked hypoalbuminemia and peripheral edema seen with the drug can also shift intravascular volume and contribute indirectly to prerenal physiology. These pathways are extrapolated from the ADC/MMAE class; agent-specific renal histopathology is not established.
Clinical presentation
When it occurs, presentation is expected to resemble nontoxic ATN: a rise in serum creatinine with bland urine sediment, possibly with low-grade proteinuria and electrolyte disturbances. Hypoalbuminemia and peripheral edema are commonly observed with the drug and may accompany or confound the renal picture.
Anticancer mechanism
Telisotuzumab vedotin is an antibody-drug conjugate (ADC) in which an antibody against c-mesenchymal-epithelial transition factor (c-Met) is linked to the microtubule inhibitor monomethyl auristatin E (MMAE). After binding c-Met on tumor cells, the conjugate is internalized and the cleavable linker liberates MMAE, which disrupts the microtubule network and triggers cell-cycle arrest and apoptosis. It received accelerated FDA approval in May 2025 for c-Met-high, EGFR wild-type nonsquamous NSCLC after prior systemic therapy.
Management
Management is supportive and follows general drug-induced ATN principles: discontinue or hold the offending agent, restore volume, remove concurrent nephrotoxins, and provide supportive care while renal function recovers. No agent-specific antidote exists. Treat associated hypoalbuminemia/edema and electrolyte abnormalities as clinically indicated.Lesion-level management framework
Risk factors
- Pre-existing chronic kidney disease
- Volume depletion or hypoalbuminemia
- Concomitant nephrotoxins (contrast, aminoglycosides, NSAIDs)
- Older age and reduced baseline renal reserve
Prevention
- Maintain euvolemia and correct hypoalbuminemia where possible
- Avoid overlapping nephrotoxins
- Baseline and periodic renal function and electrolyte monitoring
- Hold or dose-modify per label for significant toxicity
Clinical depth
Renal dose adjustment
No dedicated renal dose adjustment is established. The drug has not been formally studied in severe renal impairment or dialysis; mild-to-moderate impairment is not expected to require adjustment based on the antibody-conjugated pharmacology, but data are limited. Follow the current FDA label for dose modifications driven by toxicity.
Dialyzability & ESKD dosing
Not established. As a large antibody-drug conjugate, telisotuzumab vedotin is not expected to be appreciably dialyzable; the small-molecule MMAE payload is highly protein- and tissue-bound, so removal by hemodialysis is unlikely to be clinically meaningful.
Differential diagnosis
In a patient on Teliso-V with rising creatinine, distinguish class-extrapolated tubular injury (ATN) from prerenal azotemia driven by hypoalbuminemia, edema, and poor intake, and from concurrent nephrotoxins or contrast. Bland sediment favors ATN or prerenal physiology over glomerular or interstitial disease.
Monitoring
- Serum creatinine and eGFR at baseline and periodically
- Serum albumin
- Electrolytes
- Urinalysis for proteinuria/sediment if AKI develops
- Volume status and peripheral edema
Key trials & series
- LUMINOSITY (NCT03539536): Phase II of telisotuzumab vedotin monotherapy in previously treated c-Met-overexpressing EGFR wild-type nonsquamous NSCLC; supported accelerated approval. Predominant toxicities were peripheral neuropathy, edema, and hypoalbuminemia rather than a defined nephrotoxicity signal.
Clinical pearls
- Renal toxicity for Teliso-V is class-extrapolated from MMAE-bearing ADCs, not measured; be explicit that drug-specific renal data are thin.
- Hypoalbuminemia and peripheral edema are prominent and clinically real with this agent and can drive prerenal physiology that mimics or compounds tubular injury.
- The proximal tubule is the plausible target if liberated MMAE causes injury, consistent with the proximal/ATN signature assigned here.
- No renal dose adjustment is established; manage supportively and avoid stacking additional nephrotoxins.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Tubular Lumen
The urine flow path
Injury signatures
Acute Tubular NecrosisElectrolyte Wasting
Evidence
3 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkTelisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous-Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial.Camidge DR, Bar J, Horinouchi H, et al. · J Clin Oncol 2024 · PMID 38843488Pivotal/registrational LUMINOSITY trial defining efficacy and the safety profile; renal toxicity was not a prominent signal, supporting that renal risk is class-extrapolated.PMIDTelisotuzumab Vedotin: First Approval.Blair HA. · Drugs 2025 · PMID 40736649Summarizes the regulatory milestones, c-Met ADC mechanism, and FDA accelerated approval in c-Met-high NSCLC.PMIDAntibody-drug conjugates in lung and breast cancer: current evidence and future directions-a position statement from the ETOP IBCSG Partners Foundation.Peters S, Loi S, Andre F, et al. · Ann Oncol 2024 · PMID 38648979Class-level review of antibody-drug conjugates (including telisotuzumab vedotin) covering payload biology and toxicity considerations relevant to class-extrapolated renal risk.
Guidelines & consensus· 12
General onco-nephrology references
Acute Disease Quality InitiativeThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.SIRMSIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Radiol Med 2022 · PMID 35303246Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.Cancer Institute NSWIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.Cancer Institute NSWAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.Cancer Institute NSWA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.