Lomustine (CCNU)
Gleostine · Nitrosourea alkylator
Cumulative interstitial nephritis and CKD.
CIN
ModerateOpen →
Nitrosourea alkylator
Carmustine (BCNU)
BiCNU · BCNU
A lipophilic nitrosourea whose cumulative dose silently scleroses the kidney over months to years.
ModerateNitrosourea alkylator · approved 1977
Malignant glioma and other brain tumorsMultiple myelomaHodgkin and non-Hodgkin lymphomaStem cell transplant conditioning (e.g., BEAM/BEAC)
Signature kidney injury
Chronic Interstitial Nephropathy
Insidious, cumulative-dose chronic nephrotoxicity; in classic high-cumulative-dose series the majority of long-term survivors develop reduced renal function, with small scarred kidneys. Acute injury is uncommon except via infusion hypotension or as part of conditioning-associated TMA/HUS.
Source: Schacht et al., Cancer 1981
Mechanism of kidney injury
Cumulative chloroethyl-nitrosourea exposure produces a slowly progressive tubulointerstitial lesion - tubular atrophy, interstitial fibrosis and glomerular sclerosis - typically without a discrete acute renal failure phase or major urinary abnormalities. In the transplant setting, BCNU contributes to endothelial injury that can precipitate radiation-augmented nephritis and chemotherapy-associated HUS/TMA. Infusion-related hypotension during high-dose carmustine can additionally cause prerenal/ischemic injury.
Clinical presentation
Gradual rise in BUN/creatinine and decline in GFR, often with minimal proteinuria or bland sediment; small, scarred kidneys on imaging in advanced cases. Conditioning-associated TMA presents with schistocytes, elevated LDH, thrombocytopenia and AKI.
Onset
Delayed - months to years after cumulative exposure; conditioning-associated TMA appears within weeks.
Reversibility
Often irreversible
Anticancer mechanism
Lipophilic chloroethyl-nitrosourea that crosses the blood-brain barrier and both alkylates (interstrand DNA cross-links at O6-guanine) and carbamoylates proteins. Used for malignant gliomas and other brain tumors, multiple myeloma, lymphomas, and as a transplant-conditioning agent (e.g., BEAM/BEAC).
Management
No specific antidote; discontinue further nitrosourea and manage as chronic kidney disease with blood-pressure control and avoidance of further insults. For conditioning-associated TMA, address triggers and provide supportive care. Established fibrosis is typically irreversible and can progress after the drug is stopped.
Risk factors
- High cumulative dose (classically >=1200 mg/m2 / multiple courses)
- Prolonged treatment duration
- Concurrent or prior other nitrosoureas
- Total body irradiation / nephrotoxic co-medications (conditioning)
- Pre-existing renal impairment
Prevention
- Limit cumulative dose and track lifetime exposure
- Serial creatinine/GFR monitoring during and for years after therapy
- Maintain perfusion (avoid hypotension during high-dose infusion)
- Avoid additive nephrotoxins and minimize renal radiation dose
Note · Toxicity is cumulative-dose driven and may progress even after discontinuation; long-term renal monitoring is warranted in survivors.
Clinical depth
Renal dose adjustment
No precise CrCl-banded schema; reduce or avoid in baseline renal impairment and cap cumulative lifetime dose. Hold subsequent courses for a sustained creatinine rise rather than waiting for symptomatic CKD.
Dialyzability & ESKD dosing
Highly lipophilic, rapidly metabolized parent drug; not meaningfully removed by dialysis and dialysis is not a management strategy. ESKD use is essentially limited to individualized conditioning protocols.
Differential diagnosis
Late nitrosourea nephropathy is a bland, slowly progressive tubulointerstitial/sclerotic lesion - contrast with acute infusion-hypotension ATN (temporally tied to dosing) and with conditioning HUS/TMA (microangiopathic hemolysis, thrombocytopenia). Cumulative-dose history is the key discriminator.
Monitoring
- Serum creatinine / eGFR each course and at least annually for years after high cumulative exposure
- Blood pressure and urinalysis (late proteinuria signals established scarring)
- CBC and LDH if conditioning-associated TMA is suspected
Key trials & series
- Schacht Cancer 1981 - landmark BCNU/methyl-CCNU brain-tumor cohort defining cumulative-dose interstitial fibrosis
- Lonnerholm Bone Marrow Transplant 1991 - late renal dysfunction after BCNU-containing (BEAC) conditioning
Clinical pearls
- Renal injury is dose-cumulative and DELAYED - it can declare itself, and worsen, months to years after the last dose.
- Track lifetime nitrosourea exposure across BCNU/CCNU/methyl-CCNU; they share the same fibrotic lesion.
- A bland sediment with creeping creatinine in a glioma/lymphoma survivor should prompt review of cumulative carmustine dose.
Where it strikes
Nephron segments
Interstitium
Supporting tissue around the tubules
Injury signatures
Chronic Interstitial NephropathyThrombotic Microangiopathy
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 7272960Landmark series: progressive interstitial fibrosis and renal failure with cumulative BCNU/methyl-CCNU.PMIDRenal function after autologous bone marrow transplantation.Lonnerholm G et al. · Bone Marrow Transplant 1991 · PMID 1933054Late renal dysfunction after BCNU-containing (BEAC) conditioning plus TBI.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 1991698Mechanism: BCNU precipitates/accelerates radiation nephritis in conditioning.PMIDHemolytic uremic syndrome after high dose chemotherapy with autologous stem cell support.van der Lelie H et al. · Cancer 1995 · PMID 8635040BCNU-containing (BEAC) conditioning case of HUS/TMA with renal insufficiency.PMIDNephrotoxicity of semustine.Weiss RB et al. · Cancer Treat Rep 1983 · PMID 6360348Class data on cumulative-dose threshold and delayed onset of nitrosourea nephrotoxicity.PMIDAnticancer drug-induced kidney disorders.Kintzel PE · Drug Saf 2001 · PMID 11219485Reviews dose-related nitrosourea nephrotoxicity and infusion-hypotension contribution.
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 →