Elacestrant
Orserdu · Oral selective estrogen-receptor degrader (SERD)
2023 oral SERD; nausea-dominant, minimal intrinsic nephrotoxicity.
PRE
Mild#1 · 100% phenotype match
PROTAC estrogen-receptor degrader
Vepdegestrant
Veppanu · VPD
PROTAC estrogen-receptor degrader · approved 2026 · 2 citations
Up to date· through 2025
Thinly sourced3/9 · 3 signals
- Not met: 2 citations
- Not met: 12+ references
- Not met: Accrued over 10+ years (span: 3y)
- Not met: Beyond single case reports
- Met: High-impact journal
- Met: Landmark reference
- Met: Current through 2025
- Not met: Real-world FAERS signal
Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.
An oral estrogen-receptor PROTAC (targeted proteasomal degradation) with no meaningful nephrotoxicity.
MildPROTAC estrogen-receptor degrader
ER-positive, HER2-negative advanced or metastatic breast cancer, particularly with ESR1 mutations, after prior CDK4/6-inhibitor and endocrine therapyThe first PROTAC degrader to reach registrational breast-cancer use
§01
Signature kidney injury
Signature lesion
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
§02
Renal toxicities, ranked
This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
§03
Kidney injury
Mechanism of kidney injury
Vepdegestrant has no established direct renal toxicity. It acts by hijacking the ubiquitin-proteasome system to degrade tumor ER and is metabolized rather than renally eliminated; the kidney is neither a target of injury nor the clearance route. As with other endocrine agents, the only route to kidney trouble is indirect and non-specific — volume depletion from intercurrent GI illness or reduced intake producing prerenal azotemia — rather than any tubular, interstitial, or glomerular lesion attributable to the drug. The novel PROTAC mechanism does not introduce a known nephron-specific liability.
Clinical presentation
No characteristic renal presentation; renal function is expected to remain stable on therapy. Should a creatinine rise occur, it is typically explained by an intercurrent prerenal insult (poor intake, vomiting/diarrhea, other drugs) rather than by vepdegestrant, and it corrects with the usual supportive measures.
Management
No vepdegestrant-specific renal management is required. If a prerenal creatinine rise occurs from volume depletion, restore volume and address the precipitant; investigate a progressive rise, proteinuria, or an active sediment as a separate renal process. There is no role for dialysis or drug-specific renal rescue in relation to this agent.Lesion-level management framework
Risk factors
- 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
Prevention
- Maintain hydration during intercurrent GI illness
Anticancer mechanism· how it treats cancer
Oral proteolysis-targeting chimera (PROTAC) estrogen-receptor degrader: a bifunctional molecule that simultaneously binds estrogen receptor alpha (ERα) and an E3 ubiquitin ligase, tagging the receptor with ubiquitin so the cell's own ubiquitin-proteasome system destroys it. This catalytic degradation achieves deep, sustained ER knockdown, including in ESR1-mutant tumors, and is given orally once daily in ER-positive, HER2-negative advanced breast cancer.
§04
Clinical depth
Renal dose adjustment
No renal-impairment dose adjustment is established; vepdegestrant is an oral, metabolically cleared PROTAC and VERITAC-2 required adequate organ function. GFR is not the determinant of exposure, and dose modification is based on tolerability (hematologic, constitutional) rather than kidney function.
Dialyzability & ESKD dosing
Not characterized as dialyzable and not clinically relevant: as a large, protein-bound, metabolically cleared molecule, vepdegestrant is not expected to be removed by hemodialysis, and no renal-elimination or drug-removal scenario makes dialysis relevant for this agent.
Differential diagnosis
Any renal abnormality in a patient on vepdegestrant should be attributed to a cause other than the drug: prerenal volume depletion from intercurrent illness, a concurrent nephrotoxin, contrast, obstruction, or disease progression. Vepdegestrant is not a tubular, interstitial, or glomerular toxin, so a true renal lesion warrants an independent workup rather than reflexive attribution to the endocrine agent.
Monitoring
- 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
Key trials & series
- 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.
Clinical pearls
- 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.
Where it strikes· nephron segments & injury signatures
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
§05
References
2 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.
Evidence accrual
2 references · 2022–2025 · 1 since 2023Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.
- 1.LandmarkVepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer.Campone M, De Laurentiis M, Jhaveri K, et al. · N Engl J Med · 2025 · PMID 40454645Phase 3 VERITAC-2 registrational trial: vepdegestrant improved progression-free survival in ESR1-mutant disease with grade 3+ adverse events of 23.4% and a 2.9% discontinuation rate and no nephrotoxic signal — the basis for the 'no meaningful renal toxicity' assessment.
- 2.Acute Kidney Injury in Cancer Immunotherapy Recipients.Joseph A, Lafarge A, Azoulay E, Zafrani L. · Cells · 2022 · PMID 36552755General reference on the mechanisms by which anticancer therapies cause (and, by contrast, do not cause) kidney injury, framing why an agent like vepdegestrant — with no cytokine-release, tumor-lysis, or tubular-toxin mechanism — lacks an intrinsic renal hazard.
What gets reported — FAERS
Everything below is FAERS — adverse events someone chose to report, about 3 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.
- Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.
FAERS outcomes & reporting trend· 0 of 3 reports w/ death · 0 w/ hospitalization
3 reports is below the 50 this atlas requires before quoting a percentage, so the counts are shown instead of shares.
0 of 3
Reported with a death outcome
too few reports to express as a share
0 of 3
Reported with hospitalization
too few reports to express as a share
Reports per year
- 2015: 0 reports
- 2016: 0 reports
- 2017: 0 reports
- 2018: 0 reports
- 2019: 0 reports
- 2020: 0 reports
- 2021: 0 reports
- 2022: 0 reports
- 2023: 0 reports
- 2024: 1 reports
- 2025: 0 reports
- 2026: 2 reports
Yearly FAERS report volume · most recent year is partial.
FAERS adverse-event signal — all organ systems· 2 systems · 3 reports
Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-08-08.
Blood & lymphatic
Neutropenia2
General / constitutional
Fall1
Guidelines & consensus· 12
Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.
General onco-nephrology references
ADQIThe 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.ADDIKDIntegrating 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.ADDIKDAligning 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.ADDIKDA 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.
Where Vepdegestrant sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.
Phenotype-similar agents· the numbered markers on the map above
Profile
Zidesamtinib
Jideytro · ROS1-selective TKI
2026 TRK-sparing ROS1 TKI; no creatinine abnormality reached the label's >=20% lab-table cutoff — unlike the class's benign pseudo-AKI rise. Renally quiet so far.
PRE
Mild#2 · 89% phenotype match
Casdatifan
HIF-2α inhibitor (investigational)
Trial-stage RCC HIF-2α inhibitor; renal profile being defined.
PRE
Mild#3 · 89% phenotype match
Dordaviprone
Modeyso · Imipridone (ONC201; DRD2/ClpP)
2025 imipridone for H3 K27M glioma; renally well tolerated — QT prolongation, not nephrotoxicity, is the safety focus.
PRE
Mild#4 · 89% phenotype match
Tovorafenib
Ojemda · Type II pan-RAF (BRAF) inhibitor
2024 pediatric glioma RAF inhibitor; creatinine rise.
PRE
Mild#5 · 89% phenotype match
Tisotumab vedotin
Tivdak · Antibody-drug conjugate (tissue factor/MMAE)
Ocular/bleeding toxicity dominates; renal involvement essentially unreported.
PRE
Mild#6 · 89% phenotype match
Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.
Kidney risk across Hormonal / endocrine
Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.
- 1ElacestrantPRE — Prerenal / Hemodynamic AKIMild
- 2LeuprolideHTN — HypertensionMild
- 3Vepdegestrant· this agentPRE — Prerenal / Hemodynamic AKIMild
- 4DarolutamideLYTE — Electrolyte DisturbanceMild
- 5EnzalutamideHTN — HypertensionMild
- 6ImlunestrantPSEUDO — Pseudo-AKIMild
- 7LanreotideLYTE — Electrolyte DisturbanceMild
- 8OctreotideLYTE — Electrolyte DisturbanceMild
- 9TamoxifenSIADH — SIADH / HyponatremiaMild
- 10BicalutamideAIN — Acute Interstitial NephritisFAERS AKIMild
- 11MitotaneLYTE — Electrolyte DisturbanceModerate
- 12AbirateroneLYTE — Electrolyte DisturbanceFAERS AKIModerate
A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.