What kind of kidney injury does Zanidatamab cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome. Other reported patterns: Electrolyte Disturbance.

How should kidney function be monitored during Zanidatamab therapy?

Stool frequency/volume and weight as surrogates for volume status; Imaging review for biliary/ureteric obstruction if creatinine rises; LVEF per label (HER2-directed cardiac monitoring).

How can kidney injury from Zanidatamab be prevented?

Aggressive antidiarrheal management and hydration Correct volume status and exclude obstruction before attributing AKI to the drug

Who is at higher risk of kidney injury from Zanidatamab?

Treatment-related diarrhea and poor oral intake; Baseline CKD or volume depletion; Concurrent nephrotoxins or diuretics; Biliary/ureteric obstruction and sepsis in cholangiocarcinoma.

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Printable monograph

HER2 bispecific antibody

Zanidatamab

Ziihera · ZANI

HER2 bispecific antibody · approved 2024 · 5 citations · FAERS AKI reporting ROR 5.58 (95% CI 1.36–22.94, 2 AKI reports)

Up to date· through 2025

Deeply sourced7/9 · 6 signals

Not met: 5 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 10y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
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 biparatopic HER2 bispecific that clamps two HER2 epitopes at once — with a kidney signal that is, so far, mostly indirect.

MildHER2 bispecific antibody

HER2-positive biliary tract cancer (cholangiocarcinoma, gallbladder cancer)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

No drug-specific nephrotoxicity rate is established. In HERIZON-BTC-01 the dominant toxicities were diarrhea and infusion reactions; any AKI is expected to be largely prerenal/volume-mediated (diarrhea, reduced intake) or related to the underlying biliary obstruction, rather than a direct tubular effect.Source: Harding et al., Lancet Oncol 2023

Onset & rechallenge

Time to injuryVariable / unpredictable

Tied to GI/volume events during treatment cycles rather than a fixed latency.

Distilled from: “Variable; tied to GI/volume events during treatment cycles rather than a fixed latency.”

§02

Renal toxicities, ranked

This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Electrolyte DisturbanceSecondaryqualitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

§03

Kidney injury

Mechanism of kidney injury

No established direct nephron injury. HER2 is not a major renal tubular antigen, so antibody-mediated tubular toxicity is not expected. The plausible pathway is prerenal/hemodynamic: GI losses from diarrhea and infusion-related volume shifts reducing effective renal perfusion. In cholangiocarcinoma/gallbladder cancer, post-renal obstructive AKI from biliary/ureteric compression and sepsis-associated ischemic injury are competing, often dominant, causes.

Clinical presentation

When present, a modest reversible creatinine rise in the setting of diarrhea/volume depletion; bland urinalysis; electrolyte derangements (hypokalemia, hypomagnesemia) tracking GI losses rather than a primary tubulopathy.

Management

Largely supportive: rehydrate, control diarrhea, replace electrolytes, and hold for severe volume-mediated AKI. True intrinsic renal injury has not been characterized; evaluate for alternative causes (obstruction, sepsis, contrast, concomitant chemotherapy) before drug attribution.Lesion-level management framework

Risk factors

Treatment-related diarrhea and poor oral intake
Baseline CKD or volume depletion
Concurrent nephrotoxins or diuretics
Biliary/ureteric obstruction and sepsis in cholangiocarcinoma

Prevention

Aggressive antidiarrheal management and hydration
Correct volume status and exclude obstruction before attributing AKI to the drug

Anticancer mechanism· how it treats cancer

Humanized bispecific antibody binding two non-overlapping (biparatopic) epitopes of the HER2 ectodomain (ECD2 and ECD4), driving receptor clustering, internalization and downregulation, plus complement-dependent and antibody-dependent cellular cytotoxicity. Approved for HER2-amplified (IHC 3+) previously treated unresectable/metastatic biliary-tract cancer.

Note · 2024 approval with essentially no renal-specific literature. The prerenal/vascular signature is inferred from the GI-dominant toxicity profile and class reasoning, not from published nephrology data. Treat all renal claims as provisional.

§04

Clinical depth

Renal dose adjustment

No dedicated renal dose adjustment is specified; as a ~150 kDa monoclonal-type bispecific, clearance is not renal and exposure is not expected to change meaningfully with reduced GFR. No data in dialysis. Manage by holding/resuming for toxicity rather than CrCl-based reduction.

Dialyzability & ESKD dosing

Not dialyzable — large bispecific antibody cleared by reticuloendothelial proteolysis, not removed by hemodialysis or peritoneal dialysis. No ESKD-specific dosing guidance exists; standard dosing is reasonable with attention to volume status during infusion.

Differential diagnosis

Distinguish prerenal/diarrhea-driven AKI (low FeNa, responds to volume) from post-renal obstruction (hydronephrosis on ultrasound — common in biliary cancer) and from sepsis-associated ATN. The drug itself is rarely the primary cause.

Monitoring

Stool frequency/volume and weight as surrogates for volume status
Imaging review for biliary/ureteric obstruction if creatinine rises
LVEF per label (HER2-directed cardiac monitoring)

Key trials & series

HERIZON-BTC-01 (Harding, Lancet Oncol 2023) — pivotal phase 2b carrying the safety signal
Real-world biliary-tract cohort (Smolenschi, Eur J Cancer 2025)

Clinical pearls

In biliary-tract cancer, think obstruction and sepsis first — antibody-mediated tubular injury is not an expected mechanism.
Electrolyte loss here is GI, not tubular: replace and treat the diarrhea.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Prerenal / Hemodynamic AKI Electrolyte Disturbance

Beyond the kidney — non-renal toxicities· 3 organ systems

Class-level context for the major non-renal toxicities of the HER2 bispecific antibody class.

Immune / Infusion

CRS, infusion reactions, irAEs, anaphylaxis

Cytokine release syndrome

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

ICANS / neurotoxicity

Hematologic

Cytopenias, thrombosis, TMA

Cytopenias, hypogammaglobulinemia

§05

References

5 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

5 references · 2015–2025 · 3 since 2023

Primary (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.

FDA label — boxed warning & renal dosing· boxed warning

Quoted verbatim from this agent's current FDA label (Aug 2026) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING: DIARRHEA AND EMBRYO-FETAL TOXICITY ZIIHERA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab-jsgr, can cause severe diarrhea, including life threatening and fatal cases. Use antidiarrheal prophylaxis during the first cycle when ZIIHERA is given in combination with these drugs. Manage with antidiarrheals and supportive measures as clinically indicated. Interrupt, reduce the dose or discontinue ZIIHERA based on severity [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.5 )] . Embryo-Fetal Toxicity: Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception [see Warnings and Precautions ( 5.2 ), Use in Specific Populations ( 8.1 , 8.3 )] . WARNING: DIARRHEA and EMBRYO‑FETAL TOXICITY See full prescribing information for complete boxed warning. • ZIIHERA, in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr can cause severe diarrhea, including life threatening, and fatal cases. Use antidiarrheal prophylaxis during the first cycle when ZIIHERA is given in combination with these drugs. Manage with antidiarrheals and supportive measures as clinically indicated. Interrupt, reduce the dose or discontinue ZIIHERA based on severity. ( 2.4 , 5.1…

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 51 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.
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· 13.7% of reports w/ death · 7.8% w/ hospitalization

13.7%

Reported with a death outcome

7 of 51 reports

7.8%

Reported with hospitalization

4 of 51 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 10 systems · 51 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 5.5895% CI 1.36–22.94· 2 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Renal & urinary

Acute Kidney Injury2

General / constitutional

Chills8Pyrexia4Hyperpyrexia2

Immune / infection

Infusion Related Reaction7

Gastrointestinal

Diarrhoea6

Cardiac

Ejection Fraction Decreased3Arrhythmia1Cardiac Arrest1Cardiac Failure1

Respiratory

Oxygen Saturation Decreased2Pneumonitis2Cough1Dyspnoea1

Vascular

Gastrointestinal Haemorrhage2Blood Pressure Increased1

Musculoskeletal

Arthralgia2

Nervous system

Dizziness1Encephalopathy1

Eye

Dry Eye1Eye Inflammation1

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 Zanidatamab 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.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Zenocutuzumab

Bizengri · HER2×HER3 bispecific antibody

Profile

2024 NRG1-fusion bispecific; mostly grade 1-2 AEs — at most diarrhea-related prerenal risk, no CRS/TLS mechanism.

PRELYTE

Mild#1 · 100% phenotype match

Daratumumab

Darzalex · Anti-CD38 antibody

Profile

Tumor lysis; usable in renal impairment.

PRELYTE

Mild#2 · 97% phenotype match

Isatuximab

Sarclisa · Anti-CD38 antibody

Profile

Tumor lysis in myeloma.

PRELYTE

Mild#3 · 97% phenotype match

Imetelstat

Rytelo · Telomerase inhibitor

Profile

2024 MDS agent; tumor lysis risk.

PRELYTE

Mild#4 · 89% phenotype match

Mirdametinib

Gomekli · MEK inhibitor

Profile

2025 NF1 MEK inhibitor; creatinine rise and edema.

PRELYTE

Mild#5 · 89% phenotype match

Quizartinib

Vanflyta · FLT3 inhibitor

Profile

2023 AML FLT3 inhibitor; tumor lysis and QT.

PRELYTE

Mild#6 · 89% phenotype match

Compare Zanidatamab with its nearest agents

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.

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.