What kind of kidney injury does Temozolomide cause?

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

Is kidney injury from Temozolomide reversible?

Reversible. Typical onset: During cycles of therapy; variable..

How should kidney function be monitored during Temozolomide therapy?

Periodic serum sodium/electrolytes, especially with SIADH-promoting co-medications; Serum creatinine if a new nephrotoxin (e.g., TMP-SMX) is co-prescribed; CBC (myelosuppression is the dose-limiting toxicity, not renal injury).

How can kidney injury from Temozolomide be prevented?

Avoid unnecessary hypotonic fluids Review co-medications that promote SIADH or AIN

Who is at higher risk of kidney injury from Temozolomide?

CNS tumor/edema and concurrent SIADH-promoting drugs; Nausea/vomiting with hypotonic fluid intake; Concomitant trimethoprim-sulfamethoxazole (PJP prophylaxis) as an AIN co-factor; Older age.

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Printable monograph

Alkylator

Temozolomide

Temodar · TMZ

Alkylator · approved 1999 · 9 citations · FAERS AKI reporting ROR 1.27 (95% CI 1.10–1.47, 193 AKI reports)

Up to date· through 2025

Deeply sourced8/9 · 7 signals

Met: 9 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 28y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
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.

The glioblastoma standard that is kind to the kidney but can occasionally drop the sodium.

MildAlkylator

Glioblastoma and anaplastic astrocytomaOther malignant gliomasSelected neuroendocrine tumors (off-label combinations)

§01

Signature kidney injury

Signature lesion

SIADH / Hyponatremia

Generally renally well tolerated; renal clearance of the parent drug is a minor elimination pathway and dedicated PubMed searches for temozolomide nephrotoxicity/SIADH return essentially no indexed series. Hyponatremia/SIADH is an occasional, case/toxicity-table-level event, and rare acute interstitial nephritis has been reported in combination contexts.Source: Pouratian et al., J Neurooncol 2006

Onset & rechallenge

Time to injuryVariable / unpredictable

SIADH arises during therapy cycles with a variable, unpredictable onset.

Distilled from: “During cycles of therapy; variable.”

§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.

SIADH / Hyponatremia#1 · Signaturequalitative — no citable incidence
Inappropriate water retention at the collecting duct — high-dose cyclophosphamide.
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

Direct tubular toxicity is not characteristic; the parent drug is largely eliminated by spontaneous chemical degradation with only a minor renal pathway, underpinning its renal safety. The relevant renal-electrolyte signal is occasional SIADH-type free-water retention with dilutional hyponatremia, compounded by CNS disease, nausea/vomiting and co-medications. A rare case of acute interstitial nephritis (with nephrogenic diabetes insipidus) has been described alongside trimethoprim-sulfamethoxazole.

Clinical presentation

Hyponatremia, usually mild and detected on routine monitoring; serum creatinine typically preserved. Rarely, AIN with a rising creatinine and, in the reported case, nephrogenic diabetes insipidus.

Management

Manage hyponatremia by addressing the cause and fluid restriction; rarely requires drug interruption. For the rare AIN, withdraw the likely offender(s) and treat supportively. Renal function is generally unaffected.Lesion-level management framework

Risk factors

CNS tumor/edema and concurrent SIADH-promoting drugs
Nausea/vomiting with hypotonic fluid intake
Concomitant trimethoprim-sulfamethoxazole (PJP prophylaxis) as an AIN co-factor
Older age

Prevention

Avoid unnecessary hypotonic fluids
Review co-medications that promote SIADH or AIN

Anticancer mechanism· how it treats cancer

Oral imidazotetrazine prodrug that spontaneously hydrolyzes to the active methylating species MTIC, methylating DNA at O6- and N7-guanine; cytotoxicity depends on MGMT status and mismatch repair. Standard of care for glioblastoma and other malignant gliomas, and used in some neuroendocrine tumors.

§04

Clinical depth

Renal dose adjustment

No renal dose adjustment is established; temozolomide pharmacokinetics are dominated by non-renal chemical degradation. Standard dosing is used across normal-to-mild renal impairment, with caution and limited data in severe impairment/dialysis.

Dialyzability & ESKD dosing

Short half-life with predominantly non-renal (spontaneous hydrolysis) elimination; not a drug managed by dialysis. Limited ESKD data, but renal clearance contributes little to total elimination.

Differential diagnosis

Hyponatremia: SIADH (euvolemic, concentrated urine, natriuresis) vs cerebral salt wasting (hypovolemic, high urine output) - an important CNS-tumor distinction. A rising creatinine should prompt review for AIN from co-medications rather than attribution to temozolomide itself.

Monitoring

Periodic serum sodium/electrolytes, especially with SIADH-promoting co-medications
Serum creatinine if a new nephrotoxin (e.g., TMP-SMX) is co-prescribed
CBC (myelosuppression is the dose-limiting toxicity, not renal injury)

Key trials & series

Pivotal Stupp glioblastoma regimen (radiotherapy plus concomitant/adjuvant temozolomide) as the principal exposure context
Phase I PK trials (Dhodapkar Clin Cancer Res 1997; Brock Cancer Res 1998) showing minor renal elimination

Clinical pearls

Temozolomide is genuinely renally safe - myelosuppression, not nephrotoxicity, is the toxicity to watch.
When sodium falls in a glioma patient, distinguish SIADH from cerebral salt wasting before restricting fluids.
A creatinine bump on temozolomide is more likely from a co-prescribed nephrotoxin (e.g., TMP-SMX) than from the drug.

Where it strikes· nephron segments & injury signatures

Nephron segments

Distal Tubule / Collecting Duct

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

Injury signatures

SIADH / Hyponatremia Electrolyte Disturbance

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

Class-level context for the major non-renal toxicities of the Alkylator class.

Hematologic

Cytopenias, thrombosis, TMA

Myelosuppression; secondary malignancy risk

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

Ifosfamide encephalopathy (chloroacetaldehyde)

Cardiac

Cardiomyopathy, QT, ischemia, myocarditis

High-dose cyclophosphamide cardiotoxicity

§05

References

6 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

6 references · 1997–2021 · 2 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· 3

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.

CaseB · ModerateCentral diabetes insipidus induced by temozolomide: A report of two cases.Mahiat C et al. · J Oncol Pharm Pract 2021 · PMID 32990192Two cases of temozolomide-induced central diabetes insipidus with urinary concentration defect (polyuria/polydipsia), responsive to desmopressin and recurring on rechallenge.CaseC · LimitedCentral diabetes insipidus: a previously unreported side effect of temozolomide.Faje AT et al. · J Clin Endocrinol Metab 2013 · PMID 23928668Two index cases (plus three registry cases) of temozolomide-associated central diabetes insipidus with hypernatremia and renal urinary concentrating defect, reversible after drug discontinuation.CaseC · LimitedNephrogenic Diabetes Insipidus Associated with Temozolomide Therapy in a Patient with Grade IV Astrocytoma.Fargouche Z et al. · Eur J Case Rep Intern Med 2025 · PMID 40502960Case report of temozolomide-induced nephrogenic diabetes insipidus attributed to acute tubulointerstitial nephropathy, with polyuria and hypernatremia and a renal concentrating defect.

FDA label — boxed warning & renal dosing· renal impairment

Quoted verbatim from this agent's current FDA label (Aug 2026) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

No dosage adjustment is recommended for patients with creatinine clearance (CLcr) of 36 to 130 mL/min/m2 [see Clinical Pharmacology (12.3)]. The recommended dose of Temozolomide has not been established for patients with severe renal impairment (CLcr < 36 mL/min/m2) or for patients with end-stage renal disease on dialysis.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 20,948 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· 4 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

SIADH / Hyponatremiacorroborated · ROR 2.47 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion
Electrolyte Disturbancecorroborated · ROR 2.15 — on the terms that name the lesion (ROR 1.73)

Glomerular Injury / Proteinuria

ROR 3.0895% CI 2.50–3.79· 89 reports

SIADH / Hyponatremia

ROR 2.4795% CI 2.14–2.84· 197 reports

Acute Interstitial Nephritis

ROR 2.2595% CI 1.66–3.05· 42 reports

Electrolyte Disturbance

ROR 2.1595% CI 1.95–2.37· 406 reports

FAERS outcomes & reporting trend· 21.2% of reports w/ death · 32% w/ hospitalization

21.2%

Reported with a death outcome

4,434 of 20,948 reports

32%

Reported with hospitalization

6,699 of 20,948 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 9 systems · 20,948 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 1.2795% CI 1.10–1.47· 193 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Blood & lymphatic

Thrombocytopenia1,572Neutropenia1,035Febrile Neutropenia827Anaemia759Platelet Count Decreased623

Gastrointestinal

Nausea1,308Vomiting977Diarrhoea785Constipation463

General / constitutional

Fatigue1,037Asthenia643Pyrexia624

Nervous system

Headache553Seizure465

Immune / infection

Infection570Pneumonia433

Respiratory

Pulmonary Embolism423

Vascular

Haemorrhage401

Psychiatric

Confusional State377

Cardiac

Atrial Fibrillation376

Guidelines & consensus· 14

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.

ADQIConventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupKidney Int 2026 · PMID 41881107Cisplatin is identified as a leading cytotoxic nephrotoxin; the workgroup details preventive measures (adequate isotonic hydration, correction of volume depletion, avoidance of concurrent nephrotoxins, attention to electrolyte/magnesium wasting) and management of cisplatin-associated AKI, with a research agenda for knowledge gaps.

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 Temozolomide 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

Melphalan

Alkeran · Alkylator

Profile

SIADH in high-dose myeloma conditioning; renally cleared.

SIADHLYTE

Mild#1 · 100% phenotype match

Chlorambucil

Leukeran · Alkylating agent (nitrogen mustard)

Profile

Minimal direct nephrotoxicity; rare drug-associated SIADH/hyponatremia is the kidney-relevant signal.

SIADHLYTE

Mild#2 · 97% phenotype match

Vinblastine

Velban · Vinca alkaloid

Profile

SIADH and rare Raynaud/vascular events.

SIADHLYTE

Mild#3 · 89% phenotype match

Vincristine

Oncovin · Vinca alkaloid

Profile

SIADH → hyponatremia.

SIADHLYTE

Mild#4 · 89% phenotype match

Vinorelbine

Navelbine · Vinca alkaloid

Profile

SIADH reports.

SIADHLYTE

Mild#5 · 89% phenotype match

Vismodegib

Erivedge · Hedgehog (SMO) inhibitor

Profile

Muscle spasms; hyponatremia reported.

SIADHLYTE

Mild#6 · 87% phenotype match

Compare Temozolomide 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 Alkylating agents

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 Temozolomide’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 Temozolomide; 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 30 clinical records among all 36 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.