How should kidney function be monitored during Amivantamab therapy?

Serum magnesium, potassium and calcium each cycle (and repletion to keep ahead); Urinalysis if creatinine rises (pyuria/casts to flag AIN); Serum creatinine on therapy.

How can kidney injury from Amivantamab be prevented?

Pre-emptive potassium/magnesium repletion Review concomitant AIN-associated drugs

Who is at higher risk of kidney injury from Amivantamab?

Concurrent EGFR TKI (combination with lazertinib); Other nephrotoxins or AIN-associated drugs (PPIs, NSAIDs); Pre-existing CKD; Baseline electrolyte depletion.

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Printable monograph

EGFR-MET bispecific antibody

Amivantamab

Rybrevant · Amiv

EGFR-MET bispecific antibody · approved 2021 · 7 citations

Up to date· through 2025

Fairly sourced6/9 · 5 signals

Met: 7 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 14y)
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.

EGFR-MET bispecific antibody with class electrolyte wasting and an emerging interstitial-nephritis flag.

ModerateEGFR-MET bispecific antibody

EGFR exon 20 insertion NSCLCEGFR-mutant NSCLC (with lazertinib)

§01

Signature kidney injury

Signature lesion

Electrolyte Disturbance

Representative grade ≥3 incidence5%

In CHRYSALIS, electrolyte disturbance — notably hypokalemia (grade 3–4 in ~5%) and hypomagnesemia/hypocalcemia — was among the laboratory adverse events, consistent with EGFR-pathway inhibition. Acute interstitial nephritis is an emerging, clinician-flagged signal that is not yet quantified in the published renal literature. Reported rate: grade >=3 hypokalemia in 5% — CHRYSALIS phase I safety population, n = 114 patients with EGFR exon 20 insertion-mutated NSCLC receiving amivantamab… (Park 2021, PMID 34339292).Source: Park et al., J Clin Oncol 2021 (CHRYSALIS)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Electrolyte changes occur during and cumulatively over therapy; AIN timing is poorly characterized but presumed subacute, days-weeks after a triggering exposure by analogy to drug AIN.

Distilled from: “Electrolyte changes during therapy and cumulative; AIN timing not well characterized (subacute, days–weeks after a triggering exposure by analogy to drug AIN).”

§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.

Electrolyte Disturbance#1 · Signaturequalitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
Acute Interstitial NephritisSecondaryqualitative — no citable incidence
Immune-mediated inflammation of the renal interstitium — the signature kidney injury of checkpoint inhibitors.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

5%grade ≥3 incidence

SeverityModerate

ReversibilityVariable

Evidence7 citations

Nephron map

Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water

Interstitium

Electrolyte Disturbance

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

EGFR signaling drives the distal-convoluted-tubule magnesium channel TRPM6; EGFR blockade produces a mutated-TRPM6-like state with renal magnesium (and calcium) wasting, plus hypokalemia. This electrolyte syndrome is the established, mechanistic renal effect of EGFR-pathway inhibition. Separately, an emerging acute interstitial nephritis signal is presumed to be immune/hypersensitivity-mediated tubulointerstitial inflammation — biologically plausible given the antibody's Fc-effector and immune-directing activity — but drug-specific renal-biopsy data remain limited.

Clinical presentation

Hypomagnesemia, hypokalemia and hypocalcemia on labs (sometimes symptomatic — cramps, tetany, arrhythmia). With AIN: a subacute creatinine rise, sometimes with sterile pyuria, white-cell casts, low-grade tubular proteinuria and occasionally eosinophilia; eosinophiluria is insensitive. Infusion-related reactions are common with the first dose (non-renal).

Management

Aggressive repletion of magnesium, potassium and calcium (oral often insufficient — IV magnesium frequently required). For suspected AIN: hold the drug, exclude alternative causes, and consider corticosteroids per onconephrology guidance, ideally with biopsy confirmation when feasible.Lesion-level management framework

Risk factors

Concurrent EGFR TKI (combination with lazertinib)
Other nephrotoxins or AIN-associated drugs (PPIs, NSAIDs)
Pre-existing CKD
Baseline electrolyte depletion

Prevention

Pre-emptive potassium/magnesium repletion
Review concomitant AIN-associated drugs

Anticancer mechanism· how it treats cancer

EGFR-MET bispecific IgG1 antibody that binds the extracellular domains of both receptors, blocking ligand binding, promoting receptor internalization/degradation, and engaging Fc-mediated effector function (antibody-dependent cellular cytotoxicity/trogocytosis) — bypassing kinase-domain resistance. Approved for EGFR exon 20 insertion NSCLC and, with lazertinib, broader EGFR-mutant (exon 19 del/L858R) NSCLC.

Note · AIN is a newly recognized, clinician-flagged signal with thin published renal literature; characterization here is deliberately conservative and class-/case-based. The reliable, mechanism-anchored renal effect is EGFR-mediated electrolyte (magnesium) wasting.

§04

Clinical depth

Renal dose adjustment

No established renal dose adjustment (monoclonal antibody, not renally cleared). Manage by electrolyte repletion and infusion-rate modification; hold for suspected AIN rather than dose-reduce.

Dialyzability & ESKD dosing

Large IgG bispecific antibody — not dialyzable and cleared by reticuloendothelial proteolysis; no ESKD dose change expected. Electrolyte management is the renal priority in advanced CKD.

Differential diagnosis

EGFR-mediated electrolyte wasting (Mg/K/Ca low, bland sediment) vs antibody-related AIN (rising creatinine, pyuria/WBC casts) vs pre-renal AKI from diarrhea/poor intake; cystatin C can clarify true GFR if creatinine interpretation is uncertain. Co-administered lazertinib adds its own hyponatremia signal.

Monitoring

Serum magnesium, potassium and calcium each cycle (and repletion to keep ahead)
Urinalysis if creatinine rises (pyuria/casts to flag AIN)
Serum creatinine on therapy

Key trials & series

CHRYSALIS (Park JCO 2021) — pivotal exon 20 data with hypokalemia
MARIPOSA (amivantamab + lazertinib vs osimertinib) — combination toxicity context
PAPILLON (with chemotherapy) — frontline exon 20

Clinical pearls

Expect magnesium wasting: EGFR blockade disables distal-tubular TRPM6 — replete proactively, often with IV magnesium.
AIN is an emerging, clinician-flagged signal — a creatinine rise with sterile pyuria/casts should trigger drug-hold and nephrology referral, not just dose-reduction.
It is an antibody — no renal dosing and no dialysis removal; ESKD management is electrolyte- and AIN-focused.
In combination with lazertinib, watch sodium too — overlapping EGFR-class electrolyte effects.

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

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

Dermatologic

Rash, HFS, SJS/TEN, vitiligo

Acneiform rash, paronychia

Gastrointestinal

Diarrhea, colitis, mucositis, perforation

Diarrhea

Pulmonary

Pneumonitis, ILD, effusions, hypertension

Interstitial lung disease (EGFR TKIs)

§05

References

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

Evidence accrual

7 references · 2011–2025 · 4 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.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 3,385 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· 3 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

Acute Interstitial Nephritiscorroborated · ROR 8.33
Electrolyte Disturbancecorroborated · ROR 1.73 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion

Acute Interstitial Nephritis

ROR 8.3395% CI 5.62–12.35· 25 reports

Acute Tubular Necrosis

ROR 6.3295% CI 3.40–11.76· 10 reports

Electrolyte Disturbance

ROR 1.7395% CI 1.32–2.27· 53 reports

FAERS outcomes & reporting trend· 7.3% of reports w/ death · 19.9% w/ hospitalization

7.3%

Reported with a death outcome

247 of 3,385 reports

19.9%

Reported with hospitalization

675 of 3,385 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 3,385 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 0.6995% CI 0.43–1.11· 17 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Immune / infection

Infusion Related Reaction727

Skin

Rash495Skin Toxicity77Skin Disorder67Dermatitis Acneiform66

Gastrointestinal

Nausea110Stomatitis80Diarrhoea68Mucosal Inflammation61

Respiratory

Dyspnoea120Oxygen Saturation Decreased85Pulmonary Embolism72

General / constitutional

Fatigue77Oedema Peripheral72Asthenia64Pyrexia63

Vascular

Flushing77Hypotension76

Blood & lymphatic

Myelosuppression70

Metabolic & electrolyte

Decreased Appetite58

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 Amivantamab 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

Necitumumab

Portrazza · Anti-EGFR antibody

Profile

Severe hypomagnesemia, class effect.

LYTE

Moderate#1 · 73% phenotype match

Inavolisib

Itovebi · PI3Kα inhibitor

Profile

PI3Kα inhibitor whose renal-relevant toxicity is on-target hyperglycemia and electrolyte shifts, not a kidney lesion.

LYTE

Moderate#2 · 65% phenotype match

Denosumab

Xgeva · Anti-RANKL antibody

Profile

Severe hypocalcemia in low GFR; not directly nephrotoxic.

LYTE

Moderate#3 · 62% phenotype match

Retifanlimab

Zynyz · PD-1 immune checkpoint inhibitor

Profile

PD-1 blockade — kidney injury is immune-mediated interstitial nephritis, not direct tubular toxicity.

AINLYTEPRE

Moderate#4 · 61% phenotype match

Cetuximab

Erbitux · Anti-EGFR antibody

Profile

TRPM6 magnesium wasting.

LYTEGLOM

Mild#5 · 60% phenotype match

Panitumumab

Vectibix · Anti-EGFR antibody

Profile

TRPM6 magnesium wasting — heavier than cetuximab.

LYTEGLOM

Mild#6 · 60% phenotype match

Compare Amivantamab 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.