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Nitrosourea (alkylating)

Nimustine (ACNU)

Nidran · ACNU

Nitrosourea (alkylating) · approved 1979 · 4 references

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.

Signature injury
Chronic Interstitial Nephropathy
Severity
Moderate
Reversibility
Partially reversible
Onset
Delayed and cumulative — typically over months of repeated cycles, mirroring the nitrosourea class.

Signature kidney injury & incidence

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 is hematologic (delayed myelosuppression).

Source: Kessler et al., Rev Med Interne 1991 (class-level)

Reported injury signatures: Chronic Interstitial Nephropathy, Acute Tubular Necrosis, Electrolyte Disturbance.

Renal toxicity profile

  1. Chronic Interstitial NephropathyPrimary
  2. Acute Tubular NecrosisSecondary
  3. Electrolyte DisturbanceSecondary

Onset timing & rechallenge

Delayed (>6 weeks / cumulative) — Delayed and cumulative — typically over months of repeated cycles, like the nitrosourea class.

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.

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

  • Limit cumulative nitrosourea dose exposure

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
  • CBC (delayed, cumulative myelosuppression is dose-limiting)
  • Running tally of cumulative nitrosourea dose

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

  • 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.

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.

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.

Guidelines & consensus

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.

  • ADQI (2026) — Conventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupCisplatin 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.Kidney Int · PMID 41881107
  • ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides 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.Nat Rev Nephrol · PMID 41361704
  • SIRM (2022) — SIRM-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)Recommends 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.Radiol Med · PMID 35303246
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies 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.Kidney Int · PMID 33126977
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses 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.Kidney Int · PMID 33276867
  • ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides 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.EClinicalMedicine · PMID 40290844
  • ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree 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.EClinicalMedicine · PMID 40290845
  • ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes 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.EClinicalMedicine · PMID 40290846
  • KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/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.Crit Care · PMID 23394211
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate 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.Kidney Int · PMID 38519239
  • KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides 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.Kidney Int · PMID 34556300
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates 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.Kidney Int · PMID 38388147
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates 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.Kidney Int · PMID 38182299
  • KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages 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.Kidney Int · PMID 40975525

References

4 peer-reviewed references. Citation metadata via PubMed / NLM.

  1. 1.[Kidney disorders caused by antineoplastic agents].Nakabayashi K · Nihon Naika Gakkai Zasshi · 1994 · PMID 7814945
  2. 2.[Renal complications of anti-cancer treatments].Kessler M et al. · Rev Med Interne · 1991 · PMID 1771317
  3. 3.Local Delivery of Nimustine Hydrochloride against Brain Tumors: Basic Characterization Study.Shao X et al. · Tohoku J Exp Med · 2023 · PMID 37635063
  4. 4.Conventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis · 2021 · PMID 35190107
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.