What kind of kidney injury does Neratinib 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 Neratinib therapy?

Stool frequency and volume; weight and volume status, especially in the first cycle; Serum creatinine, potassium and magnesium during diarrheal episodes; LFTs periodically (hepatotoxicity); Adherence to loperamide prophylaxis.

How can kidney injury from Neratinib be prevented?

Loperamide prophylaxis from day 1 (and/or dose-escalation of neratinib per CONTROL) Patient education on early antidiarrheal use and hydration Electrolyte monitoring and repletion (potassium, magnesium) Dose interruption/reduction for grade 3+ diarrhea

Who is at higher risk of kidney injury from Neratinib?

Absence of antidiarrheal prophylaxis; Pre-existing CKD, diuretic use or baseline volume depletion; Concurrent capecitabine (additive GI toxicity); Older age and frailty.

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Printable monograph

HER2 / pan-EGFR TKI

Neratinib

Nerlynx · NER

HER2 / pan-EGFR TKI · approved 2017 · 6 citations · FAERS AKI reporting ROR 2.55 (95% CI 1.88–3.46, 42 AKI reports)

Aging evidence· through 2022

Fairly sourced5/9 · 5 signals

Met: 6 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 6y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2022
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.

Irreversible pan-HER/EGFR TKI whose severe diarrhea is the renal villain — dehydration drives prerenal AKI, mitigated by loperamide prophylaxis.

ModerateIrreversible pan-HER TKI era

Extended adjuvant therapy of early-stage HER2-positive breast cancer after trastuzumabAdvanced/metastatic HER2-positive breast cancer (with capecitabine)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Diarrhea is near-universal without prophylaxis: in ExteNET, grade 3 diarrhea occurred in ~40% without antidiarrheal prophylaxis, falling substantially with loperamide and dose-escalation strategies (CONTROL). The resulting volume-depletion prerenal AKI is not separately quantified.Source: Chan et al., Lancet Oncol 2016 (ExteNET); Barcenas et al., Ann Oncol 2020 (CONTROL)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Prerenal AKI follows early diarrhea (first days-to-weeks).

Distilled from: “Diarrhea characteristically within the first days-to-weeks; prerenal AKI follows uncontrolled fluid loss.”

§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

Pan-HER/EGFR inhibition disrupts EGFR-dependent chloride and fluid handling in the intestinal epithelium, producing secretory diarrhea (a class effect of EGFR-pathway inhibitors). Profuse early diarrhea causes extracellular volume depletion, sodium/potassium/magnesium losses and prerenal azotemia; severe sustained hypovolemia can progress to ischemic ATN. The kidney injury is hemodynamic/electrolyte-mediated, not a direct neratinib nephrotoxicity.

Clinical presentation

Early-onset (often first cycle), high-volume watery diarrhea, dehydration, orthostasis and electrolyte loss (hypokalemia, hypomagnesemia); creatinine rises with a low FeNa and concentrated urine typical of prerenal physiology.

Management

Aggressive antidiarrheal therapy (loperamide, adding budesonide/colestipol per CONTROL), oral/IV rehydration and electrolyte correction; hold or reduce neratinib for severe diarrhea. Restore volume to reverse prerenal AKI; persistent injury despite euvolemia should prompt evaluation for ATN. Prophylaxis is the key preventive measure.Lesion-level management framework

Risk factors

Absence of antidiarrheal prophylaxis
Pre-existing CKD, diuretic use or baseline volume depletion
Concurrent capecitabine (additive GI toxicity)
Older age and frailty

Prevention

Loperamide prophylaxis from day 1 (and/or dose-escalation of neratinib per CONTROL)
Patient education on early antidiarrheal use and hydration
Electrolyte monitoring and repletion (potassium, magnesium)
Dose interruption/reduction for grade 3+ diarrhea

Anticancer mechanism· how it treats cancer

Oral irreversible inhibitor of HER1 (EGFR), HER2 and HER4 that covalently binds the kinase cysteine residue, providing sustained pan-HER blockade. Used as extended adjuvant therapy after trastuzumab in HER2-positive breast cancer and in metastatic disease.

Note · The renal link is indirect: neratinib causes severe secretory diarrhea, and AKI arises from dehydration/electrolyte loss rather than a direct renal lesion. No neratinib-specific AKI paper exists; diarrhea-prophylaxis trials carry the signal.

§04

Clinical depth

Renal dose adjustment

No dose adjustment for mild-moderate renal impairment; severe impairment/ESKD not well studied (hepatic CYP3A4 metabolism). Dose changes are driven by diarrhea and hepatotoxicity.

Dialyzability & ESKD dosing

Highly protein-bound; not expected to be dialyzable. No established ESKD dosing.

Differential diagnosis

Distinguish prerenal AKI from diarrhea (volume-responsive, low FeNa) from infectious diarrhea, capecitabine-related GI toxicity, and intrinsic ATN if hypoperfusion is prolonged. The first-cycle, high-volume secretory pattern is characteristic.

Monitoring

Stool frequency and volume; weight and volume status, especially in the first cycle
Serum creatinine, potassium and magnesium during diarrheal episodes
LFTs periodically (hepatotoxicity)
Adherence to loperamide prophylaxis

Key trials & series

ExteNET (Chan, Lancet Oncol 2016) — registrational extended-adjuvant trial defining the grade 3 diarrhea signal
CONTROL (Barcenas, Ann Oncol 2020) — antidiarrheal prophylaxis/dose-escalation reducing diarrhea

Clinical pearls

Diarrhea is the dominant, dose-limiting toxicity — loperamide prophylaxis from day 1 transforms tolerability.
The kidney injury is volume- and electrolyte-mediated; rehydration and magnesium/potassium repletion are central.
CONTROL-style dose-escalation reduces the diarrhea burden as effectively as antidiarrheals.
Watch magnesium and potassium — losses are easy to miss and compound the AKI.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Distal Tubule / Collecting Duct

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

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 / pan-EGFR TKI 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

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

Evidence accrual

6 references · 2016–2022 · 2 since 2020

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 2,294 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· 1 signal

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

Electrolyte Disturbancecorroborated · ROR 4.85 — on the terms that name the lesion (ROR 11.96)
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 4.8595% CI 3.96–5.94· 98 reports

FAERS outcomes & reporting trend· 15.7% of reports w/ death · 29.6% w/ hospitalization

15.7%

Reported with a death outcome

360 of 2,294 reports

29.6%

Reported with hospitalization

678 of 2,294 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 2,294 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 2.5595% CI 1.88–3.46· 42 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Gastrointestinal

Diarrhoea1,249Nausea554Vomiting313Constipation277Abdominal Pain119

General / constitutional

Fatigue473Weight Decreased138Asthenia102Pyrexia74

Metabolic & electrolyte

Decreased Appetite253Dehydration147Hypokalaemia68

Nervous system

Headache116Dizziness103Neuropathy Peripheral94

Skin

Rash99

Respiratory

Cough86

Musculoskeletal

Muscle Spasms74

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 Neratinib 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

Sevabertinib

Hyrnuo · HER2/EGFR TKI

Profile

2025 reversible HER2/EGFR TKI; profuse diarrhea (84-91%) → prerenal AKI, plus EGFR-pathway renal magnesium wasting.

PRELYTE

Mild#1 · 94% phenotype match

Strontium-89 chloride

Metastron · Bone-seeking radiopharmaceutical

Profile

Renally excreted, so caution in renal impairment; myelosuppression is the dominant toxicity.

LYTEPRE

Moderate#2 · 87% phenotype match

Mitotane

Lysodren · Adrenolytic

Profile

Indirect: hypoadrenalism drives hyponatremia/prerenal; cisplatin nephrotoxicity in EDP-M.

LYTEPRE

Moderate#3 · 85% phenotype match

Glasdegib

Daurismo · Hedgehog (SMO) inhibitor

Profile

QT prolongation and muscle spasms; AML.

PRELYTE

Mild#4 · 83% phenotype match

Darolutamide

Nubeqa · Androgen receptor inhibitor (ARSI)

Profile

Not nephrotoxic; exposure rises in severe renal impairment, so consider dose adaptation.

LYTEPRE

Mild#5 · 83% phenotype match

Gedatolisib

Revtorpyk · Pan-PI3K inhibitor

Profile

2026 IV pan-PI3K + mTORC1/2 (breast); on-target hyperglycemia and low-grade Na/K/Mg drift — creatinine up 14% vs 8% control, grade 3-4 rare.

LYTEPRE

Mild#6 · 83% phenotype match

Compare Neratinib 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 EGFR / HER2 inhibitors

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.