What kind of kidney injury does Necitumumab cause?

Electrolyte Disturbance — Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

How should kidney function be monitored during Necitumumab therapy?

Serum magnesium before every dose and for >=8 weeks after the last dose; Serum calcium and potassium each cycle; ECG/QT in severe or symptomatic hypomagnesemia.

How can kidney injury from Necitumumab be prevented?

Proactive oral magnesium supplementation in those with falling levels Attention to and correction of concurrent cisplatin-related losses

Who is at higher risk of kidney injury from Necitumumab?

Concurrent cisplatin (additive renal magnesium wasting); Prolonged duration of EGFR-antibody therapy; Diarrhea or poor oral intake; Baseline low magnesium.

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Printable monograph

Anti-EGFR antibody

Necitumumab

Portrazza · NECI

Anti-EGFR antibody · approved 2015 · 9 citations

Aging evidence· through 2021

Fairly sourced6/9 · 5 signals

Met: 9 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 14y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2021
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 second-generation anti-EGFR antibody whose hallmark renal-electrolyte toxicity is severe, TRPM6-mediated hypomagnesemia.

ModerateAnti-EGFR antibody

Metastatic squamous non-small cell lung cancer (first-line, with gemcitabine + cisplatin)

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Signature kidney injury

Signature lesion

Electrolyte Disturbance

Representative grade ≥3 incidence9%

Grade 3-4 hypomagnesemia occurred in about 9% of patients receiving necitumumab plus chemotherapy versus 1% with chemotherapy alone in the pivotal SQUIRE trial; any-grade hypomagnesemia is likely more frequent (as a class, anti-EGFR antibodies are associated with a gradual magnesium fall in many patients over time).Source: Thatcher et al., Lancet Oncol 2015

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Magnesium wasting develops cumulatively over weeks of repeated dosing and worsens with continued therapy.

Distilled from: “Develops cumulatively over weeks of repeated dosing and worsens with continued therapy; magnesium should be checked before each dose and for at least 8 weeks after completion because deficits can persist.”

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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.

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).

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Kidney injury

Mechanism of kidney injury

A mechanistic class effect of EGFR blockade. EGF, processed and basolaterally secreted by the distal convoluted tubule, is a magnesiotropic hormone that activates the apical TRPM6 magnesium channel; blocking the EGFR with necitumumab removes this stimulus, reducing TRPM6-mediated active magnesium reabsorption and producing renal magnesium wasting (inappropriately high fractional excretion of magnesium) and hypomagnesemia. Resultant intracellular magnesium depletion impairs PTH secretion/action and renal potassium handling, generating secondary hypocalcemia and hypokalemia.

Clinical presentation

Low serum magnesium, sometimes profound and symptomatic (weakness, neuromuscular irritability/tetany, prolonged QT and arrhythmia risk), with inappropriately high 24-hour urinary magnesium or fractional excretion of magnesium >2-4% despite hypomagnesemia; frequently accompanied by refractory hypocalcemia and hypokalemia. Frank AKI is not the characteristic injury.

Management

Replace magnesium—oral magnesium salts for mild deficits, intravenous magnesium sulfate for severe (<1.0 mg/dL) or symptomatic ones—and correct accompanying hypocalcemia and hypokalemia (which are often refractory until magnesium is restored). Hold dosing for severe hypomagnesemia until corrected, and continue monitoring after treatment because the channel defect and deficits can persist for weeks.Lesion-level management framework

Risk factors

Concurrent cisplatin (additive renal magnesium wasting)
Prolonged duration of EGFR-antibody therapy
Diarrhea or poor oral intake
Baseline low magnesium

Prevention

Proactive oral magnesium supplementation in those with falling levels
Attention to and correction of concurrent cisplatin-related losses

Anticancer mechanism· how it treats cancer

Recombinant human IgG1 monoclonal antibody against the epidermal growth factor receptor (EGFR), blocking ligand binding and downstream RAS/MAPK and PI3K/AKT proliferative signaling. Approved with gemcitabine and cisplatin for first-line metastatic squamous non-small cell lung cancer.

Note · The dominant renal-electrolyte signal is hypomagnesemia rather than a structural nephropathy; this is shared across anti-EGFR antibodies (cetuximab, panitumumab) and is mechanistically identical to inherited TRPM6/EGF-related hypomagnesemia.

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Clinical depth

Renal dose adjustment

No renal dose adjustment of the antibody is defined; necitumumab is not renally cleared. Management is electrolyte repletion and dose holds for severe hypomagnesemia rather than mg/kg reduction. Concurrent cisplatin requires its own CrCl-based dosing/hydration.

Dialyzability & ESKD dosing

Not dialyzable—a ~145 kDa IgG1 monoclonal antibody cleared by reticuloendothelial catabolism, not removed by hemodialysis; no supplemental dosing after HD. (Magnesium itself is small and dialyzable, but the toxicity is renal wasting, not retention.)

Differential diagnosis

Distinguish EGFR-antibody renal magnesium wasting (high FE-Mg) from gastrointestinal magnesium loss (diarrhea, low FE-Mg) and from cisplatin tubulopathy (which adds magnesium wasting plus ATN). Refractory hypocalcemia/hypokalemia that corrects only after magnesium repletion is a clue to underlying hypomagnesemia.

Monitoring

Serum magnesium before every dose and for >=8 weeks after the last dose
Serum calcium and potassium each cycle
ECG/QT in severe or symptomatic hypomagnesemia

Key trials & series

SQUIRE phase 3 trial (Thatcher Lancet Oncol 2015)
Tejpar Lancet Oncol 2007 anti-EGFR antibody magnesium-wasting cohort (class)
Crosnier Cancers 2021 VigiBase EGFR renal-safety pharmacovigilance

Clinical pearls

The lesion is electrolyte, not structural: think distal-tubule magnesium wasting, not AKI.
Hypomagnesemia begets refractory hypocalcemia and hypokalemia—always replete magnesium first.
Check a fractional excretion of magnesium: it is inappropriately high (>2%) with EGFR-antibody wasting.

Where it strikes· nephron segments & injury signatures

Nephron segments

Distal Tubule / Collecting Duct

Fine-tuning of Na, K, Mg, acid & water

Injury signatures

Electrolyte Disturbance

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

Class-level context for the major non-renal toxicities of the Anti-EGFR 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)

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References

8 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

8 references · 2007–2021 · 1 since 2019

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.

Case reports — ranked by strength· 1

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseC · LimitedLung squamous cell carcinoma with severe hypomagnesemia due to cisplatin plus gemcitabine in combination with necitumumab therapy: A case report.Nakao A et al. · Thorac Cancer 2021 · PMID 34061460Single-patient case report of asymptomatic grade 4 hypomagnesemia (renal electrolyte wasting) developing on necitumumab plus cisplatin/gemcitabine, with detailed clinical course of the magnesium-wasting adverse event.

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 Necitumumab 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

Denosumab

Xgeva · Anti-RANKL antibody

Profile

Severe hypocalcemia in low GFR; not directly nephrotoxic.

LYTE

Moderate#1 · 89% 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 · 86% phenotype match

Amivantamab

Rybrevant · EGFR-MET bispecific antibody

Profile

EGFR-mediated electrolyte (magnesium) wasting; an emerging acute interstitial nephritis signal is also clinician-flagged.

LYTEAIN

Moderate#3 · 73% phenotype match

Cetuximab

Erbitux · Anti-EGFR antibody

Profile

TRPM6 magnesium wasting.

LYTEGLOM

Mild#4 · 71% phenotype match

Panitumumab

Vectibix · Anti-EGFR antibody

Profile

TRPM6 magnesium wasting — heavier than cetuximab.

LYTEGLOM

Mild#5 · 71% phenotype match

Erdafitinib

Balversa · FGFR inhibitor

Profile

Hyperphosphatemia is an on-target class effect.

LYTE

Moderate#6 · 66% phenotype match

Compare Necitumumab 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.