Carmustine (BCNU)
BiCNU · Nitrosourea alkylator
Delayed interstitial fibrosis with high cumulative dose.
CINTMA
ModerateOpen →
Nitrosourea alkylator
Lomustine (CCNU)
Gleostine · CCNU
An oral nitrosourea cousin of carmustine that scars the interstitium dose by cumulative dose.
ModerateNitrosourea alkylator · approved 1976
Malignant glioma and other primary brain tumorsHodgkin lymphoma
Signature kidney injury
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
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. Experimental models confirm CCNU glomerular and tubular injury, accentuated when combined with anthracyclines.
Clinical presentation
Insidious rise in creatinine and decline in GFR, often with bland urinalysis; may be detected only on routine labs months after therapy.
Onset
Delayed - months to years; dose-cumulative.
Reversibility
Often irreversible
Anticancer mechanism
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.
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.
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
- Serial renal function monitoring during and after treatment
- Avoid additive nephrotoxins
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.
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 (eosinophiluria, 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
Interstitium
Supporting tissue around the tubules
Injury signatures
Chronic Interstitial Nephropathy
Beyond the kidney
Class-level context for the major non-renal toxicities of nitrosourea alkylators.
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
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkNephrotoxicity of nitrosoureas.Schacht RG et al. · Cancer 1981 · PMID 7272960Documents progressive interstitial renal disease across nitrosoureas including CCNU-class agents.PMIDCCNU-adriamycin association induces earlier and more severe nephropathy in rats.Raguenez-Viotte G et al. · Arch Toxicol 1988 · PMID 3377683Experimental lomustine (CCNU) glomerular/tubular injury, augmented by anthracycline.PMIDChronic interstitial nephritis in agricultural communities is a toxin-induced proximal tubular nephropathy.Vervaet BA et al. · Kidney Int 2019 · PMID 31892415Names lomustine among nephrotoxins producing the proximal-tubular lysosomal lesion.PMIDNephrotoxicity of semustine.Weiss RB et al. · Cancer Treat Rep 1983 · PMID 6360348Cumulative-dose threshold and delayed-onset nephrotoxicity for the methyl-CCNU/nitrosourea family.PMIDInfluence of nephrotoxic drugs on the late renal toxicity associated with bone marrow transplant conditioning regimens.Moulder JE et al. · Int J Radiat Oncol Biol Phys 1991 · PMID 1991698Class evidence that chloroethyl-nitrosoureas precipitate/accelerate late conditioning-related renal injury.PMIDAnticancer drug-induced kidney disorders.Kintzel PE · Drug Saf 2001 · PMID 11219485Onconephrology review listing chloroethyl-nitrosoureas as dose-related nephrotoxins.
Related agents
Other agents sharing the same signature kidney injury.
Profile
Lutetium-177 Dotatate
Lutathera · Radioligand therapy (PRRT)
Peptide receptor radionuclide therapy; proximal tubular radiation nephropathy is dose-limiting — amino-acid co-infusion is renoprotective.
CINTMA
ModerateOpen →
Lutetium-177 PSMA-617 (vipivotide)
Pluvicto · Radioligand therapy (PSMA)
PSMA-targeted radioligand for prostate cancer; renal radiation exposure and xerostomia.
CINLYTE
ModerateOpen →