What kind of kidney injury does Osimertinib cause?

SIADH / Hyponatremia — Inappropriate water retention at the collecting duct — high-dose cyclophosphamide. Other reported patterns: Electrolyte Disturbance, Pseudo-AKI.

How should kidney function be monitored during Osimertinib therapy?

Serum sodium at baseline and periodically, especially in the first 1-3 months; Serum and urine osmolality plus urine sodium if hyponatremia develops.

How can kidney injury from Osimertinib be prevented?

Review and minimize concomitant hyponatremia-inducing drugs

Who is at higher risk of kidney injury from Osimertinib?

Concurrent medications that promote hyponatremia (thiazides, SSRIs); Older age; Volume/solute status predisposing to dilutional hyponatremia.

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Printable monograph

EGFR TKI

Osimertinib

Tagrisso · OSI

EGFR TKI · approved 2015 · 9 citations

Up to date· through 2026

Deeply sourced7/9 · 6 signals

Met: 9 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 11y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2026
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 third-generation EGFR TKI whose uncommon renal-electrolyte signal is SIADH-type hyponatremia.

MildEGFR TKI

EGFR exon 19 deletion / L858R-mutant non-small cell lung cancer (first-line)EGFR T790M-positive NSCLC after prior EGFR-TKIAdjuvant therapy of resected EGFR-mutant NSCLC

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Signature kidney injury

Signature lesion

SIADH / Hyponatremia

Syndrome of inappropriate antidiuretic hormone (SIADH)-type hyponatremia is described at the case level; occasional acute kidney injury and rare proteinuria are reported. True structural kidney injury is not quantified as a discrete endpoint in randomized data, where overall renal adverse events are uncommon. The common osimertinib renal finding is instead a pseudo-decrease in creatinine-based eGFR from inhibited tubular creatinine secretion, quantified for osimertinib specifically by Ilyas et al. (Kidney Med 2026) and, at the cohort level, in the AMBORA real-world analysis: among 238 patients on 38 oral antitumor agents likely to cause pseudo-worsening, mean eGFR fell 6.8 mL/min within 30 days and by >=20 mL/min in 17.2% — a whole-group figure, not an osimertinib-specific rate.Source: Skribek et al., Lung Cancer 2022

Onset & rechallenge

Time to injuryDelayed (>6 weeks / cumulative)

Within roughly the first weeks to a few months (around two months in several published cases).

Distilled from: “Reported within roughly the first weeks to a few months of therapy (around two months in several published cases).”

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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.

SIADH / Hyponatremia#1 · Signatureno population incidence denominator
SIADH reported only at case level; a rare adverse effect PMID 35276629 (opens PubMed in a new tab)
Electrolyte DisturbanceRareno population incidence denominator
SIADH-mediated hyponatremia described only in case reports PMID 33839042 (opens PubMed in a new tab)
Pseudo-AKISecondaryno population incidence denominator
Inhibited tubular creatinine secretion lowers creatinine-based eGFR without a true GFR fall; the AMBORA cohort figure (mean eGFR -6.8 mL/min within 30 days, >=20 mL/min in 17.2%) spans 38 oral antitumor agents, not osimertinib alone PMID 42179809 (opens PubMed in a new tab)

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityMild

ReversibilityReversible

Evidence9 citations

Nephron map

Proximal Tubule

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

SIADH / Hyponatremia

Inappropriate water retention at the collecting duct — high-dose cyclophosphamide.

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Kidney injury

Deep diveDrug-induced SIADH: the sodium falls and the tumour takes the blameHyponatremia is the commonest electrolyte disorder in oncology and its commonest explanation is the cancer itself — which is exactly why a drug that impairs free-water excretion can go on being given for months while the sodium is treated as a feature of the disease.

Mechanism of kidney injury

Mechanism is incompletely understood. Reported cases show a euvolemic SIADH pattern—impaired free-water excretion with hypotonic hyponatremia, inappropriately concentrated urine, and natriuresis—that resolves with fluid restriction and drug discontinuation and may recur on rechallenge, implicating drug-associated inappropriate antidiuresis (possibly via EGFR effects on collecting-duct water handling) rather than direct tubular destruction. Distinct, rare AKI/glomerular cases reflect the broader EGFR-TKI nephrotoxicity spectrum.

Clinical presentation

Hyponatremia with low serum osmolality, inappropriately elevated urine osmolality, and urine sodium typically >30-40 mmol/L in a clinically euvolemic patient with normal thyroid/adrenal axes; symptoms range from none to nausea, headache, confusion, or seizures when sodium is severe or falls rapidly. Occasional creatinine rises are reported separately.

Management

Confirm the SIADH pattern (serum and urine osmolality, urine sodium, volume status) and exclude adrenal/thyroid and other causes; institute fluid restriction and correct sodium at a safe rate (avoid overcorrection). Hold or discontinue osimertinib for significant or symptomatic hyponatremia; dose-reduced rechallenge or an alternative EGFR TKI may be considered after resolution.Lesion-level management framework

Risk factors

Concurrent medications that promote hyponatremia (thiazides, SSRIs)
Older age
Volume/solute status predisposing to dilutional hyponatremia

Prevention

Review and minimize concomitant hyponatremia-inducing drugs

Anticancer mechanism· how it treats cancer

Third-generation, irreversible EGFR tyrosine kinase inhibitor that covalently binds the C797 residue and is selective for sensitizing EGFR mutations and the T790M resistance mutation while sparing wild-type EGFR. Standard therapy for EGFR-mutant non-small cell lung cancer, including CNS disease.

Note · The kidney signal is primarily electrolyte (hyponatremia via SIADH) rather than structural nephrotoxicity; the SIADH evidence is limited to case reports, so its incidence is unquantified.

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Clinical depth

Renal dose adjustment

No osimertinib dose adjustment is required for mild-to-moderate renal impairment; data in severe impairment/ESKD are limited (hepatic CYP3A metabolism predominates). Management of SIADH is fluid restriction and dose hold, not renal dose modification.

Dialyzability & ESKD dosing

Not appreciably dialyzable—a small but highly lipophilic, extensively protein-bound molecule with a very large volume of distribution; minimal renal excretion of parent drug, so hemodialysis is not expected to remove clinically relevant amounts.

Differential diagnosis

Separate osimertinib-induced SIADH from hypovolemic hyponatremia (prerenal, low urine sodium), thiazide- or SSRI-induced hyponatremia, paraneoplastic SIADH from the underlying lung cancer or brain metastases, and adrenal insufficiency. The temporal link to drug start, euvolemia, and resolution on withdrawal supports drug attribution.

Monitoring

Serum sodium at baseline and periodically, especially in the first 1-3 months
Serum and urine osmolality plus urine sodium if hyponatremia develops

Key trials & series

FLAURA (Soria NEJM 2017) first-line registrational trial
Skribek Lung Cancer 2022 and Takao Clin Lung Cancer 2021 SIADH case reports
Crosnier Cancers 2021 VigiBase EGFR renal-safety pharmacovigilance

Clinical pearls

Osimertinib's renal fingerprint is hyponatremia via SIADH, not AIN or ATN.
Always exclude paraneoplastic SIADH from the lung cancer itself and from CNS metastases before blaming the drug.
Fluid restriction plus a drug hold usually fixes it; correct sodium slowly to avoid osmotic demyelination.
A falling creatinine-based eGFR on osimertinib is usually pseudo-AKI from blocked tubular creatinine secretion — confirm with cystatin C before calling it nephrotoxicity or holding an effective drug. A modest true AKI/proteinuria signal does exist across EGFR TKIs, so still check the urinalysis.

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

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

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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 · 2015–2026 · 2 since 2024

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 · LimitedSyndrome of inappropriate secretion of antidiuretic hormone (SIADH) by osimertinib and continued treatment with dose reduction for postoperative recurrence of lung adenocarcinoma: a case report.Nishii M et al. · Transl Lung Cancer Res 2025 · PMID 41132965Osimertinib-induced SIADH with hyponatremia that resolved on discontinuation and was managed by dose reduction without recurrence.

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 Osimertinib 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

Lazertinib

Lazcluze · EGFR TKI (3rd-gen)

Profile

2024 EGFR TKI; hyponatremia like osimertinib.

SIADHLYTE

Mild#1 · 69% phenotype match

Melphalan

Alkeran · Alkylator

Profile

SIADH in high-dose myeloma conditioning; renally cleared.

SIADHLYTE

Mild#2 · 62% phenotype match

Temozolomide

Temodar · Alkylator

Profile

Occasional SIADH; generally renally well tolerated.

SIADHLYTE

Mild#3 · 62% phenotype match

Vinblastine

Velban · Vinca alkaloid

Profile

SIADH and rare Raynaud/vascular events.

SIADHLYTE

Mild#4 · 62% phenotype match

Vincristine

Oncovin · Vinca alkaloid

Profile

SIADH → hyponatremia.

SIADHLYTE

Mild#5 · 62% phenotype match

Vinorelbine

Navelbine · Vinca alkaloid

Profile

SIADH reports.

SIADHLYTE

Mild#6 · 62% phenotype match

Compare Osimertinib 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.

Who studies this

The leading contributors to Osimertinib’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Osimertinib; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 25 clinical records among all 31 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.