Elotuzumab
Empliciti · Anti-SLAMF7 mAb
Kidney-neutral antibody; unchanged PK in severe impairment and dialysis; no renal dose adjustment.
PRE
Mild#1 · 94% phenotype match
Anti-Claudin-18.2 monoclonal antibody
Zolbetuximab
Vyloy · Zolb
Anti-Claudin-18.2 monoclonal antibody · approved 2024 · 4 citations
Up to date· through 2025
Thinly sourced3/9 · 3 signals
- Not met: 4 citations
- Not met: 12+ references
- Not met: Accrued over 10+ years (span: 2y)
- Met: Beyond single case reports
- Not met: Peer-reviewed sources
- 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.
A Claudin-18.2 antibody whose renal risk is indirect — severe nausea and vomiting driving prerenal AKI.
ModerateAnti-Claudin-18.2 monoclonal antibody
CLDN18.2-positive HER2-negative gastric/GEJ adenocarcinoma
§01
Signature kidney injury
Signature lesion
Direct nephrotoxicity is not a recognized feature. The defining, dose-limiting toxicity in the pivotal SPOTLIGHT and GLOW trials is severe nausea and vomiting (an on-target effect on gastric mucosa), which can cause volume depletion and prerenal acute kidney injury. A quantified renal-injury rate is not reported; the renal risk is mechanistic/indirect.Source: Shah et al., Nat Med 2023 (GLOW); nausea/vomiting-driven volume depletion
Onset & rechallenge
Time to injuryAcute (~1–7 days)
Prerenal AKI around infusions, especially the first cycles, tracking the nausea/vomiting peak.
Distilled from: “Around infusions, especially the first cycles, tracking the nausea/vomiting peak.”
§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
Claudin-18.2 is also expressed in normal gastric mucosa, so zolbetuximab provokes prominent nausea and vomiting, especially with the first infusions. The resulting fluid and electrolyte losses cause hypovolemia and a prerenal/hemodynamic AKI; sustained hypovolemia can progress to ischemic tubular injury. There is no characteristic intrinsic tubular or glomerular lesion attributable to the antibody itself, and it is not renally cleared.
Clinical presentation
A prerenal creatinine rise in the context of severe nausea/vomiting with clinical volume depletion (orthostasis, low urine output, high BUN:creatinine ratio), typically around infusions. Electrolyte disturbances from vomiting (hypokalemia, metabolic alkalosis) may accompany it.
Management
Volume resuscitation and antiemetics for prerenal AKI; reduce infusion rate or interrupt for severe nausea/vomiting per label. Correct vomiting-related electrolyte disturbances. Injury is generally reversible with timely volume repletion; coordinate with concurrent platinum nephrotoxicity management.Lesion-level management framework
Risk factors
- Severe nausea/vomiting (drug-specific, on-target)
- Inadequate antiemetic prophylaxis
- Pre-existing CKD
- Concurrent nephrotoxic chemotherapy (platinum) and volume depletion
Prevention
- Aggressive antiemetic prophylaxis (including infusion-rate reduction/interruption)
- Hydration around infusions
- Coordinate with platinum-chemotherapy hydration protocols
Anticancer mechanism· how it treats cancer
Chimeric IgG1 monoclonal antibody targeting Claudin-18.2, a tight-junction protein exposed on gastric and gastroesophageal adenocarcinoma cells. Binding triggers antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Given with chemotherapy (e.g., CAPOX/mFOLFOX6) for CLDN18.2-positive, HER2-negative locally advanced/metastatic gastric or GEJ adenocarcinoma.
Note · No zolbetuximab-specific renal study exists; the renal concern is indirect (severe nausea/vomiting to volume depletion to prerenal AKI), drawn from pivotal-trial adverse-event data. Treat prerenal AKI as a mechanistic inference, not a directly reported endpoint.
§04
Clinical depth
Renal dose adjustment
No dedicated renal dose adjustment is established; mild–moderate impairment does not require change and severe impairment/ESKD are not well studied. Management is antiemetic control and volume repletion rather than fixed renal dosing.
Dialyzability & ESKD dosing
The IgG1 antibody is not dialyzable and is cleared by proteolysis; no ESKD dose change is defined. Dialysis would support AKI management, not drug removal.
Differential diagnosis
Prerenal AKI from nausea/vomiting volume loss (hypovolemia, fluid-responsive) vs concurrent platinum-chemotherapy tubular injury (ATN) vs unrelated intrinsic renal disease; zolbetuximab has no characteristic renal lesion of its own, and the vomiting time-course is the clue.
Monitoring
- Nausea/vomiting severity and volume status around infusions
- Coordinate with platinum-chemotherapy renal monitoring
Key trials & series
- GLOW (Shah Nat Med 2023) — pivotal phase 3 with CAPOX
- SPOTLIGHT — pivotal phase 3 with mFOLFOX6 (overall context)
Clinical pearls
- Control the vomiting, protect the kidney: zolbetuximab's renal risk is volume depletion from on-target gastric-mucosa nausea/vomiting.
- It is usually given with platinum chemotherapy — separate the prerenal (vomiting) and tubular (platinum) contributions.
Where it strikes· nephron segments & injury signatures
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
§05
References
4 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.
Evidence accrual
4 references · 2023–2025 · 4 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.LandmarkZolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial.Shah MA et al. · Nat Med · 2023 · PMID 37524953Pivotal phase 3; nausea/vomiting the dominant treatment-emergent toxicity (volume-depletion/prerenal risk).
- 2.SPOTlight on GLOW.Derks S et al. · Cell Rep Med · 2023 · PMID 37852180Commentary integrating SPOTLIGHT and GLOW data, including the prominent GI (nausea/vomiting) toxicity.
- 3.Zolbetuximab-clzb: Targeting Claudin 18.2 in Advanced Gastric and Gastroesophageal Adenocarcinoma.Gorwitz GL et al. · Ann Pharmacother · 2025 · PMID 40426305Drug review summarizing the nausea/vomiting-dominant safety profile relevant to prerenal AKI risk.
- 4.Renal Side Effects of Novel Molecular Targeted Oncologic Agents.Fenoglio R et al. · G Ital Nefrol · 2023 · PMID 38007829Onconephrology review for framing renal effects of targeted/biologic agents.
What gets reported — FAERS
Everything below is FAERS — adverse events someone chose to report, about 1,293 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.
- Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
- Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
- 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 reported renal phenotypes· 2 signals
Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.
What reporting says about this profile's documented lesions
- Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
Electrolyte Disturbance
ROR 4.2895% CI 3.22–5.70· 49 reports
SIADH / Hyponatremia
ROR 2.2395% CI 1.23–4.03· 11 reports
FAERS outcomes & reporting trend· 12.4% of reports w/ death · 33.9% w/ hospitalization
12.4%
Reported with a death outcome
160 of 1,293 reports
33.9%
Reported with hospitalization
438 of 1,293 reports
Reports per year
- 2015: 0 reports
- 2016: 0 reports
- 2017: 0 reports
- 2018: 0 reports
- 2019: 7 reports
- 2020: 6 reports
- 2021: 22 reports
- 2022: 5 reports
- 2023: 6 reports
- 2024: 100 reports
- 2025: 772 reports
- 2026: 375 reports
Yearly FAERS report volume · most recent year is partial.
FAERS adverse-event signal — all organ systems· 6 systems · 1,293 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 2026-10-01.
Disproportionality (acute kidney injury):ROR 1.3995% CI 0.80–2.40· 13 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).
Gastrointestinal
Nausea499Vomiting237Diarrhoea73Abdominal Pain46Gastritis40
Metabolic & electrolyte
Decreased Appetite175Hypoalbuminaemia108Dehydration43
General / constitutional
Oedema Peripheral60Malaise54Fatigue44Weight Decreased44Oedema43
Blood & lymphatic
Neutrophil Count Decreased57Myelosuppression54Platelet Count Decreased35
Nervous system
Neuropathy Peripheral33
Respiratory
Dyspnoea32
Guidelines & consensus· 13
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 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.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 Zolbetuximab 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
Denileukin diftitox
Lymphir · Immunotoxin (IL-2–diphtheria)
Capillary-leak syndrome → prerenal AKI.
PRE
Moderate#2 · 89% phenotype match
Tebentafusp
Kimmtrak · Bispecific T-cell engager (gp100×CD3 ImmTAC)
CRS-driven hypotension → prerenal AKI early in dosing; uveal melanoma.
PRE
Moderate#3 · 89% phenotype match
Trifluridine/tipiracil
Lonsurf · Oral fluoropyrimidine + TP inhibitor
Tipiracil is renally cleared; reduced GFR raises exposure and early severe neutropenia; dose-reduce in renal impairment.
PRE
Moderate#4 · 88% phenotype match
Tovorafenib
Ojemda · Type II pan-RAF (BRAF) inhibitor
2024 pediatric glioma RAF inhibitor; creatinine rise.
PRE
Mild#5 · 84% 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#6 · 83% 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 Monoclonal antibodies (other)
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.
- 1DaratumumabPRE — Prerenal / Hemodynamic AKIMild
- 2MogamulizumabPRE — Prerenal / Hemodynamic AKIMild
- 3ZenocutuzumabPRE — Prerenal / Hemodynamic AKIMild
- 4ElotuzumabPRE — Prerenal / Hemodynamic AKIFAERS AKIMild
- 5CetuximabLYTE — Electrolyte DisturbanceFAERS AKIMild
- 6IsatuximabPRE — Prerenal / Hemodynamic AKIFAERS AKIMild
- 7PanitumumabLYTE — Electrolyte DisturbanceFAERS AKIMild
- 8TafasitamabPRE — Prerenal / Hemodynamic AKIFAERS AKIMild
- 9ZanidatamabPRE — Prerenal / Hemodynamic AKIFAERS AKIMild
- 10NecitumumabLYTE — Electrolyte DisturbanceModerate
- 11Zolbetuximab· this agentPRE — Prerenal / Hemodynamic AKIModerate
- 12AmivantamabLYTE — Electrolyte DisturbanceModerate
- 13NaxitamabPRE — Prerenal / Hemodynamic AKIModerate
- 14DinutuximabPRE — Prerenal / Hemodynamic AKIFAERS AKIModerate
- 15ObinutuzumabXTAL — Crystal / Obstructive NephropathyFAERS AKIModerate
- 16RituximabXTAL — Crystal / Obstructive NephropathyFAERS 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.