Vepdegestrant

Prerenal / Hemodynamic AKI.

Vepdegestrant carries no meaningful renal signal and no discrete published incidence of drug-related acute kidney injury. In the phase 3 VERITAC-2 trial (Campone, N Engl J Med 2025; n=624) grade 3 or higher adverse events occurred in 23.4% of patients — modestly above fulvestrant (17.6%) — and only 2.9% discontinued for adverse events, with a profile dominated by hematologic and constitutional effects rather than a nephrotoxic one. Any renal contribution would be indirect (for example, prerenal physiology if a patient became volume-depleted from an intercurrent illness), not an intrinsic kidney toxicity of the drug.

Source: No meaningful renal signal; grade 3+ AEs 23.4% with 2.9% discontinuation in VERITAC-2 (Campone 2025), profile not nephrotoxic

Reported injury signatures: Prerenal / Hemodynamic AKI.

• Intercurrent volume depletion (vomiting, diarrhea, poor intake) causing prerenal physiology
• Baseline CKD (lowers reserve for any intercurrent insult)
• Concurrent nephrotoxins or true renal insults unrelated to the drug

• Maintain hydration during intercurrent GI illness
• Review co-medications for nephrotoxins if renal function changes
• Routine chemistry monitoring as part of standard oncologic care

• Routine serum creatinine as part of standard care (no drug-specific renal surveillance required)
• Volume status during intercurrent GI illness
• Standard tolerability monitoring (blood counts, constitutional symptoms) that drives dose changes

• VERITAC-2 (Campone, N Engl J Med 2025) — phase 3 trial of vepdegestrant versus fulvestrant in ER-positive, HER2-negative advanced breast cancer (n=624); vepdegestrant improved progression-free survival in the ESR1-mutant subgroup with grade 3+ adverse events of 23.4% and a 2.9% discontinuation rate — a tolerability profile without a nephrotoxic signal.

• First-of-its-kind mechanism, unremarkable kidney story: vepdegestrant degrades the ER via the proteasome and leaves the nephron alone.
• A creatinine rise on vepdegestrant is almost always something else — look for volume depletion or another nephrotoxin.
• Its dose is modified for blood counts and tolerability, not for GFR.
• There is no dialysis or renal-rescue scenario tied to this drug.
• A grounded 'kidney-safe' answer is the useful takeaway when a patient on vepdegestrant is being risk-assessed.

• ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides 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.Nat Rev Nephrol · PMID 41361704
• SIRM (2022) — SIRM-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)Recommends 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.Radiol Med · PMID 35303246
• KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies 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.Kidney Int · PMID 33126977
• KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses 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.Kidney Int · PMID 33276867
• ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides 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.EClinicalMedicine · PMID 40290844
• ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree 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.EClinicalMedicine · PMID 40290845
• ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes 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.EClinicalMedicine · PMID 40290846
• KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/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.Crit Care · PMID 23394211
• KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides 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.Kidney Int · PMID 34556300
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates 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.Kidney Int · PMID 38388147
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates 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.Kidney Int · PMID 38182299
• KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages 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.Kidney Int · PMID 40975525