What kind of kidney injury does Lomustine (CCNU) cause?

Chronic Interstitial Nephropathy — Slow, cumulative tubulointerstitial scarring — fibrosis, tubular atrophy and glomerulosclerosis with no discrete acute phase. The nitrosourea (carmustine/lomustine) lesion and delayed radioligand (radiation) nephropathy; often irreversible and detected only as a creeping creatinine months to years later.

Is kidney injury from Lomustine (CCNU) reversible?

Often irreversible. Typical onset: Delayed - months to years; dose-cumulative..

How should kidney function be monitored during Lomustine (CCNU) therapy?

Serum creatinine / eGFR before each ~6-weekly course and on long-term follow-up; CBC (delayed nadir at 4-6 weeks) and blood pressure; Urinalysis for late proteinuria signaling established scarring.

How can kidney injury from Lomustine (CCNU) be prevented?

Cap and track cumulative lifetime nitrosourea dose

Who is at higher risk of kidney injury from Lomustine (CCNU)?

High cumulative dose / prolonged therapy; Concurrent or prior other nitrosoureas (shared lifetime exposure); Concurrent anthracycline or other nephrotoxins; Pre-existing renal impairment.

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Printable monograph

Nitrosourea alkylator

Lomustine (CCNU)

Gleostine · CCNU

Nitrosourea alkylator · approved 1976 · 9 citations

Dated evidence· through 2019

Fairly sourced6/9 · 5 signals

Met: 9 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 40y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2019
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.

An oral nitrosourea cousin of carmustine that scars the interstitium dose by cumulative dose.

ModerateNitrosourea alkylator

Malignant glioma and other primary brain tumorsHodgkin lymphoma

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Signature kidney injury

Signature lesion

Chronic Interstitial Nephropathy

Chronic, cumulative-dose nephrotoxicity analogous to carmustine; high-dose/long-duration exposure causes interstitial fibrosis and progressive CKD. Acute injury is uncommon and lomustine-specific incidence is not precisely quantified - the clinical signal is reported under the nitrosourea class.Source: Schacht et al., Cancer 1981

Onset & rechallenge

Time to injuryDelayed (>6 weeks / cumulative)

Dose-cumulative nephropathy months to years out.

Distilled from: “Delayed - months to years; dose-cumulative.”

Long-term outlook & thresholds

Renal recoveryOften permanent

The nitrosourea tubulointerstitial/fibrotic injury has no specific reversal and can progress even after the drug is stopped; it is managed as established chronic kidney disease.PMID 7272960 (opens PubMed in a new tab)

CKD trajectory.: High-dose or long-duration exposure causes interstitial fibrosis and progressive CKD; injury is delayed and detected months to years after therapy.

Early-detection biomarkers

Urinary KIM-1 (kidney injury molecule-1) — Proximal tubular injury. Lomustine's lesion is a proximal tubular / tubulointerstitial injury that presents with bland urinalysis and only an insidious creatinine rise; urinary KIM-1 is a sensitive, specific marker of proximal tubular damage that can flag injury before overt GFR decline.PMID 20930626 (opens PubMed in a new tab)
Urinary β2-microglobulin (low-molecular-weight proteinuria) — Proximal tubular reabsorptive dysfunction. Low-molecular-weight proteins are freely filtered and normally reclaimed by the proximal tubule; their appearance in urine signals subclinical proximal tubular dysfunction ahead of a measurable creatinine change. The rationale is PRECLINICAL and not nitrosourea-specific: the cited study measured twelve urinary markers in rats given puromycin aminonucleoside or cisplatin (no nitrosourea), and its ROC analysis singled out KIM-1 rather than β2-microglobulin as the best proximal-tubular marker — so read this as a mechanistic case for LMW-proteinuria monitoring, not a validated lomustine test.PMID 20438795 (opens PubMed in a new tab)

Long-term outcome and threshold data distilled from the agent's cited literature — educational, not a substitute for the primary sources.

Recovery across agents

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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.

Chronic Interstitial Nephropathy#1 · Signaturequalitative — no citable incidence
Slow, cumulative tubulointerstitial scarring — fibrosis, tubular atrophy and glomerulosclerosis with no discrete acute phase. The nitrosourea (carmustine/lomustine) lesion and delayed radioligand (radiation) nephropathy; often irreversible and detected only as a creeping creatinine months to years later.

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Kidney injury

Mechanism of kidney injury

Cumulative nitrosourea exposure drives a slowly progressive tubulointerstitial nephritis/fibrosis with proximal tubular injury, tubular atrophy and glomerulosclerosis, typically lacking an acute phase or prominent urinary findings - the same chloroethyl-nitrosourea lesion documented across the class. In experimental models CCNU alone was not directly nephrotoxic but accelerated and worsened anthracycline-induced glomerular and tubular injury.

Clinical presentation

Insidious rise in creatinine and decline in GFR, often with bland urinalysis; may be detected only on routine labs months after therapy.

Management

Stop further nitrosourea exposure and manage as chronic kidney disease (blood-pressure control, avoid further insults); no specific reversal. Fibrotic injury can progress despite discontinuation.Lesion-level management framework

Risk factors

High cumulative dose / prolonged therapy
Concurrent or prior other nitrosoureas (shared lifetime exposure)
Concurrent anthracycline or other nephrotoxins
Pre-existing renal impairment

Prevention

Cap and track cumulative lifetime nitrosourea dose

Anticancer mechanism· how it treats cancer

Oral lipophilic chloroethyl-nitrosourea that alkylates (interstrand DNA cross-links) and carbamoylates proteins, crossing the blood-brain barrier. Used for brain tumors (gliomas, including in PCV regimens) and Hodgkin lymphoma.

Note · Renal-toxicity data are largely extrapolated from the nitrosourea class (BCNU, methyl-CCNU, semustine); dedicated lomustine-only clinical renal series essentially do not exist.

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Clinical depth

Renal dose adjustment

Reduce or avoid in baseline renal impairment; the oral dose is given at long (~6-week) intervals partly to limit cumulative marrow and organ toxicity. Cap lifetime cumulative dose and hold for a sustained creatinine rise.

Dialyzability & ESKD dosing

Lipophilic, rapidly metabolized; not meaningfully dialyzable and dialysis is not a rescue strategy. ESKD experience is anecdotal.

Differential diagnosis

As with carmustine, a bland, slowly progressive tubulointerstitial/sclerotic lesion tied to cumulative dose; distinguish from acute drug-induced AIN (sterile pyuria, white-cell casts, abrupt onset, often other agents) and from prerenal physiology. Cumulative nitrosourea history is decisive.

Monitoring

Serum creatinine / eGFR before each ~6-weekly course and on long-term follow-up
CBC (delayed nadir at 4-6 weeks) and blood pressure
Urinalysis for late proteinuria signaling established scarring

Key trials & series

Schacht Cancer 1981 - nitrosourea cohort (MeSH-indexed for lomustine) defining progressive interstitial disease
PCV-regimen glioma experience (procarbazine-CCNU-vincristine) as the principal clinical exposure context

Clinical pearls

Class-equivalent to carmustine for the kidney - the relevant number is total lifetime nitrosourea dose, not any single course.
Injury is delayed and can progress after the drug is stopped; follow renal function long after treatment ends.
Bland sediment with slow GFR decline in a treated glioma patient should prompt a cumulative-CCNU tally.

Where it strikes· nephron segments & injury signatures

Nephron segments

Interstitium

Supporting tissue around the tubules

Injury signatures

Chronic Interstitial Nephropathy

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

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

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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 · 1981–2019 · 1 since 2017

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.

CaseC · LimitedNephrotoxicity of lomustine. A case report and literature review.Ellis ME et al. · Cancer Chemother Pharmacol 1985 · PMID 4017166Patient developed chronic nephrotoxicity (glomerular/interstitial injury) after high cumulative-dose lomustine (CCNU) for brain astrocytoma.CaseC · Limited[Chronic renal failure after CCNU treatment (author's transl)].Goupil A et al. · Nouv Presse Med 1980 · PMID 7443446Terminal chronic renal failure with normal baseline function after cumulative CCNU 1940 mg/m2, illustrating dose-dependent chronic nephropathy.CaseC · LimitedCCNU nephrotoxicity following sustained remission in oat cell carcinoma.Silver HK et al. · Cancer Treat Rep 1979 · PMID 221116Chronic renal failure developing after long-term lomustine (CCNU) in a small-cell lung cancer survivor in remission.

FDA label — boxed warning & renal dosing· boxed warning

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

Boxed warning

WARNING: DELAYED MYELOSUPPRESSION and RISK OF OVERDOSAGE DELAYED MYELOSUPPRESSION Lomustine causes myelosuppression including fatal myelosuppression. Myelosuppression is delayed, dose-related, and cumulative; occurring 4 to 6 weeks after drug administration and persisting for 1 to 2 weeks. Thrombocytopenia is generally more severe than leukopenia. Cumulative myelosuppression from lomustine is manifested by greater severity and longer duration of cytopenias. Monitor blood counts for at least 6 weeks after each dose. Do not give lomustine more frequently than every 6 weeks [see Warnings and Precautions ( 5.1 ), Dosage and Administration ( 2.2 , 2.3 )] . RISK OF OVERDOSAGE PRESCRIBE, DISPENSE, AND ADMINISTER ONLY ENOUGH CAPSULES FOR ONE DOSE. Fatal toxicity occurs with overdosage of lomustine . Both physician and pharmacist should emphasize to the patient that only one dose of lomustine is taken every 6 weeks [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.2 ), Overdosage ( 10 )] . WARNING: DELAYED MYELOSUPPRESSION and RISK OF OVERDOSAGE See full prescribing information for complete boxed warning. Delayed Myelosuppression Lomustine causes myelosuppression including fatal myelosuppression. Myelosuppression is delayed, dose-related, and cumulative. Thrombocytopenia is generally more severe than leukopenia. Monitor blood counts and do not give lomustine more…

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 2,533 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· 2 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

Chronic Interstitial NephropathyNot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

Glomerular Injury / Proteinuria

ROR 3.7195% CI 2.15–6.41· 13 reports

SIADH / Hyponatremia

ROR 1.8695% CI 1.17–2.95· 18 reports

FAERS outcomes & reporting trend· 22.7% of reports w/ death · 21% w/ hospitalization

22.7%

Reported with a death outcome

575 of 2,533 reports

21%

Reported with hospitalization

531 of 2,533 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 2,533 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 0.7195% CI 0.41–1.22· 13 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Blood & lymphatic

Thrombocytopenia180Neutropenia130Platelet Count Decreased112Anaemia64White Blood Cell Count Decreased56

Gastrointestinal

Nausea228Vomiting107Constipation72Diarrhoea67Mucosal Inflammation39

General / constitutional

Fatigue211Asthenia58Weight Decreased53Pyrexia49

Nervous system

Seizure88Headache86

Immune / infection

Pneumonia48Infection41

Skin

Rash55

Metabolic & electrolyte

Decreased Appetite52

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 Lomustine (CCNU) 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

Carmustine (BCNU)

BiCNU · Nitrosourea alkylator

Profile

Delayed interstitial fibrosis with high cumulative dose.

CINTMA

Moderate#1 · 76% phenotype match

Fotemustine

Muphoran · Nitrosourea (alkylating)

Profile

Class delayed cumulative tubulointerstitial/ATN; usually mild; acute signal often really cisplatin.

CINATNLYTE

Moderate#2 · 56% phenotype match

Nimustine (ACNU)

Nidran · Nitrosourea (alkylating)

Profile

Water-soluble nitrosourea; renal risk inferred at class level; cumulative delayed tubulointerstitial injury; DLT is myelosuppression.

CINATNLYTE

Moderate#3 · 56% phenotype match

Lutetium-177 PSMA-617 (vipivotide)

Pluvicto · Radioligand therapy (PSMA)

Profile

PSMA-targeted radioligand for prostate cancer; renal radiation exposure and xerostomia.

CINLYTE

Moderate#4 · 51% phenotype match

Lutetium-177 Dotatate

Lutathera · Radioligand therapy (PRRT)

Profile

Peptide receptor radionuclide therapy; proximal tubular radiation nephropathy is dose-limiting — amino-acid co-infusion is renoprotective.

CINTMA

Moderate#5 · 45% phenotype match

Pemetrexed

Alimta · Antifolate

Profile

Cumulative chronic tubulointerstitial injury; RTA and nephrogenic DI.

CINATNLYTE

Moderate#6 · 42% phenotype match

Compare Lomustine (CCNU) 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.