Osimertinib

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

Reported injury signatures: SIADH / Hyponatremia, Electrolyte Disturbance, Pseudo-AKI.

1. SIADH / HyponatremiaPrimarySIADH reported only at case level; a rare adverse effect
2. Electrolyte DisturbanceRareSIADH-mediated hyponatremia described only in case reports
3. Pseudo-AKISecondaryInhibited 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

Delayed (>6 weeks / cumulative) — Within roughly the first weeks to a few months (around two months in several published cases).

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

• Review and minimize concomitant hyponatremia-inducing drugs

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

• 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

• 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.

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.

• ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides 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.Nat Rev Nephrol · PMID 41361704
• SIRM (2022) — SIRM-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)Recommends 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.Radiol Med · PMID 35303246
• KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies 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.Kidney Int · PMID 33126977
• KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses 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.Kidney Int · PMID 33276867
• ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides 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.EClinicalMedicine · PMID 40290844
• ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree 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.EClinicalMedicine · PMID 40290845
• ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes 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.EClinicalMedicine · PMID 40290846
• KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/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.Crit Care · PMID 23394211
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate 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.Kidney Int · PMID 38519239
• KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides 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.Kidney Int · PMID 34556300
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates 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.Kidney Int · PMID 38388147
• KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates 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.Kidney Int · PMID 38182299
• KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages 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.Kidney Int · PMID 40975525