Carmustine (BCNU)
BiCNU · Nitrosourea alkylator
Delayed interstitial fibrosis with high cumulative dose.
CINTMA
ModerateOpen →
Nitrosourea (alkylating)
Nimustine (ACNU)
Nidran · ACNU
A water-soluble nitrosourea workhorse for gliomas — its renal risk is inferred from the class (cumulative tubulointerstitial injury) because drug-specific human renal data are genuinely thin.
Moderate1979 (Japan) nitrosourea · approved 1979
Malignant glioma / glioblastoma (frequently with radiotherapy)Other CNS malignancies and selected systemic tumors (regimen-dependent)
Signature kidney injury
Chronic Interstitial Nephropathy
Drug-specific human renal-toxicity data for nimustine are thin; renal risk is asserted largely at the class level. Like other nitrosoureas, cumulative dosing is associated with delayed tubulointerstitial injury and CKD, but a reliable nimustine-specific incidence is not established. Dose-limiting toxicity in practice is hematologic (delayed myelosuppression).
Source: Kessler et al., Rev Med Interne 1991 (class-level)
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityModerate
ReversibilityPartially reversible
Evidence0 refs
Nephron map
Proximal Tubule
Distal Tubule / Collecting Duct
InterstitiumSupporting tissue around the tubules
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.
Mechanism of kidney injury
By analogy to the nitrosourea class, nimustine and its reactive alkylating/carbamoylating species can injure renal tubular epithelium and interstitium, producing cumulative, dose-related tubulointerstitial nephritis and tubular injury that can progress to interstitial fibrosis with high lifetime exposure. Direct mechanistic and quantitative human renal data specific to nimustine are limited; preclinical pharmacokinetic work characterizes distribution and clearance rather than nephrotoxicity.
Clinical presentation
When present, the expected pattern is a slowly progressive creatinine rise with tubular dysfunction rather than acute oliguric failure; the class can lead to chronic interstitial nephritis after prolonged cumulative exposure. Acute, drug-attributable AKI is not a well-documented feature.
Onset
Delayed and cumulative — typically over months of repeated cycles, mirroring the nitrosourea class.
Reversibility
Partially reversible
Anticancer mechanism
Nimustine (ACNU) is a water-soluble chloroethyl-nitrosourea alkylating agent. It alkylates DNA (chloroethylation at O6-guanine) to form interstrand cross-links, causing cell-cycle-independent cytotoxicity; its water solubility and CNS penetration make it a mainstay (especially historically and in Asia/Europe) for malignant gliomas, often combined with radiotherapy.
Management
No specific antidote. Treat as class-level tubulointerstitial injury: hold or discontinue for progressive renal dysfunction, give supportive care and volume repletion, and continue surveillance after therapy given the delayed pattern.
Risk factors
- High cumulative nitrosourea dose
- Pre-existing renal impairment
- Concomitant nephrotoxins
- Older age and volume depletion
Prevention
- Track and limit cumulative nitrosourea dose
- Baseline and serial renal function plus urinalysis, including long-term follow-up
- Maintain hydration
- Avoid concurrent nephrotoxins where possible
Note · Explicitly a class-level inference: published nimustine-specific renal-injury literature is sparse, and much available pharmacokinetic data is preclinical (e.g., convection-enhanced delivery studies). Counsel and monitor based on the established nitrosourea nephrotoxicity paradigm rather than robust nimustine-specific numbers.
Clinical depth
Renal dose adjustment
Use caution in renal impairment; nimustine-specific renal dose thresholds are not well defined. Limit cumulative exposure and withhold for evolving renal dysfunction; individualize per protocol.
Dialyzability & ESKD dosing
Not well characterized. Although nimustine is comparatively water-soluble, it is rapidly metabolized with a short plasma half-life, so dialysis is not an established removal strategy; manage by dose limitation and monitoring.
Differential diagnosis
Separate delayed nitrosourea tubulointerstitial injury from concurrent nephrotoxins, prerenal azotemia, and obstructive or tumor-related causes. The expected nimustine pattern, when present, is the cumulative, delayed interstitial phenotype of the class — not acute crystalline or glomerular injury.
Monitoring
- Serum creatinine / eGFR at baseline and across cycles, with delayed surveillance
- Urinalysis for tubular dysfunction
- Electrolytes
- CBC (delayed, cumulative myelosuppression is dose-limiting)
Key trials & series
- Kessler & Netter 1991 — class-level review listing nitrosoureas among nephrotoxic cytotoxics (basis for nimustine's inferred renal risk)
- Shao et al. 2023 — preclinical pharmacokinetics/clearance of nimustine hydrochloride (ACNU) via convection-enhanced delivery
- Gupta et al. 2021 — onconephrology review framing alkylating-agent tubulointerstitial/CKD risk
Clinical pearls
- Nimustine's renal risk is largely a class inference — say so: dedicated human renal data are sparse.
- Like all nitrosoureas, the danger is cumulative and delayed, so follow renal function beyond active treatment.
- Day-to-day dose-limiting toxicity is delayed myelosuppression, not nephrotoxicity.
- Water solubility aids CNS delivery but does not make the kidney a reliable elimination route to exploit therapeutically.
Where it strikes
Nephron segments
Interstitium
Supporting tissue around the tubules
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Chronic Interstitial NephropathyAcute Tubular NecrosisElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of nitrosourea (alkylating)s.
Ophthalmic
Keratopathy, uveitis, retinopathy
- Visual disturbance (crizotinib)
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- CNS effects (lorlatinib)
Evidence
3 peer-reviewed references. Citation metadata via PubMed / NLM.
PMID[Renal complications of anti-cancer treatments].Kessler M et al. · Rev Med Interne 1991 · PMID 1771317Class-level review identifying nitrosoureas as a frequent, dose-limiting cause of nephrotoxicity — the basis for nimustine's inferred renal risk.PMIDLocal Delivery of Nimustine Hydrochloride against Brain Tumors: Basic Characterization Study.Shao X et al. · Tohoku J Exp Med 2023 · PMID 37635063Characterizes nimustine (ACNU) distribution and clearance (preclinical), underscoring that available nimustine-specific data are pharmacokinetic rather than renal-toxicity outcomes.LandmarkConventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis 2021 · PMID 35190107Authoritative onconephrology review of conventional chemotherapy kidney complications, framing the tubulointerstitial/CKD risks relevant to alkylating nitrosoureas.
Related agents
Other agents sharing the same signature kidney injury.
Profile
Lomustine (CCNU)
Gleostine · Nitrosourea alkylator
Cumulative interstitial nephritis and CKD.
CIN
ModerateOpen →
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 →