Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Anti-Claudin-18.2 monoclonal antibody
Zolbetuximab
Vyloy · Zolb
A Claudin-18.2 antibody whose renal risk is indirect — severe nausea and vomiting driving prerenal AKI.
ModerateAnti-Claudin-18.2 monoclonal antibody · approved 2024
CLDN18.2-positive HER2-negative gastric/GEJ adenocarcinoma
Signature kidney injury
Prerenal / Hemodynamic AKI
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
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. Characterization is conservative given the absence of renal-specific literature.
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.
Onset
Around infusions, especially the first cycles, tracking the nausea/vomiting peak.
Reversibility
Reversible
Anticancer mechanism
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.
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.
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
- Monitor creatinine and electrolytes each cycle
- Coordinate with platinum-chemotherapy hydration protocols
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. Incidence is not quantified.
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
- Serum creatinine/eGFR and electrolytes each cycle
- 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.
- Infusion-rate reduction/interruption and antiemetics are the key preventive levers.
- It is usually given with platinum chemotherapy — separate the prerenal (vomiting) and tubular (platinum) contributions.
- It is an antibody — no renal dosing or dialysis removal; renal incidence is not quantified.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKI
Evidence
4 peer-reviewed references. Citation metadata via PubMed / NLM.
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).PMIDSPOTlight on GLOW.Derks S et al. · Cell Rep Med 2023 · PMID 37852180Commentary integrating SPOTLIGHT and GLOW data, including the prominent GI (nausea/vomiting) toxicity.PMIDZolbetuximab-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.PMIDRenal 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.
Related agents
Other agents sharing the same signature kidney injury.