What kind of kidney injury does Altretamine (hexamethylmelamine) cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

How should kidney function be monitored during Altretamine (hexamethylmelamine) therapy?

Neurologic examination for peripheral/central neurotoxicity; CBC for myelosuppression; Assessment of nausea/vomiting and volume status.

How can kidney injury from Altretamine (hexamethylmelamine) be prevented?

Maintain hydration, especially given prominent emetogenicity Antiemetic prophylaxis to prevent prerenal volume depletion Account for cisplatin co-toxicity when interpreting creatinine changes

Who is at higher risk of kidney injury from Altretamine (hexamethylmelamine)?

Concurrent or prior cisplatin exposure (the dominant nephrotoxic confounder); Pre-existing kidney impairment; Volume depletion from drug-induced vomiting; Older age and reduced renal reserve.

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Printable monograph

Alkylating agent (methylmelamine)

Altretamine (hexamethylmelamine)

Hexalen · ALT

Alkylating agent (methylmelamine) · approved 1990 · 3 citations

Dated evidence· through 2017Legacy

Largely superseded — little used in modern platinum-resistant ovarian-cancer regimens; ~2–3 papers/year over the last five years. Intrinsic renal toxicity is mild and not well established as an independent entity.

Fairly sourced5/9 · 4 signals

Not met: 3 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 26y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2017
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.

Oral melamine antineoplastic for ovarian cancer; dose-limiting toxicities are neurologic and GI, with only mild, reversible renal changes reported.

Mildclassic-cytotoxic

Persistent or recurrent ovarian cancer after first-line platinum/alkylator-based therapy (single-agent salvage)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Altretamine is not regarded as substantially nephrotoxic. Mild, generally reversible elevations in serum creatinine have been noted in trials, but the dose-limiting toxicities are gastrointestinal (nausea/vomiting), neurologic (peripheral and central neurotoxicity) and hematologic. No reliable renal incidence figure is established, and reported renal changes are confounded by frequent combination with cisplatin.Source: Lee et al., Drugs 1995 (renal effects mild, confounded by cisplatin); not quantified

Onset & rechallenge

Time to injuryVariable / unpredictable

Mild creatinine changes tend to occur during cycles and reverse after dosing, with poorly defined timing.

Distilled from: “Any mild creatinine change tends to occur during cycles and to reverse after dosing; timing is not well defined.”

§02

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.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

§03

Kidney injury

Mechanism of kidney injury

No characteristic, well-defined tubular lesion is attributed to altretamine. Mild reversible creatinine rises may reflect modest, transient tubular effects of reactive metabolites, but because altretamine has frequently been studied alongside cisplatin, attributing renal changes to altretamine alone is difficult. The predominant organ toxicities are neurologic and gastrointestinal.

Clinical presentation

Usually no overt renal syndrome; at most a mild, reversible creatinine increase. Clinically dominant features are nausea/vomiting, peripheral neuropathy and CNS symptoms, plus myelosuppression.

Management

Manage any mild renal change supportively with hydration and antiemesis; dose modification is generally driven by neurologic and GI toxicity rather than kidney function. No specific renal antidote is required.Lesion-level management framework

Risk factors

Concurrent or prior cisplatin exposure (the dominant nephrotoxic confounder)
Pre-existing kidney impairment
Volume depletion from drug-induced vomiting
Older age and reduced renal reserve

Prevention

Maintain hydration, especially given prominent emetogenicity
Antiemetic prophylaxis to prevent prerenal volume depletion
Account for cisplatin co-toxicity when interpreting creatinine changes

Anticancer mechanism· how it treats cancer

Methylmelamine that requires hepatic microsomal N-demethylation to generate reactive methylol and formaldehyde intermediates; these are thought to act as alkylating species damaging DNA, though it is not directly cross-resistant with classical alkylators.

Note · Neurotoxicity (peripheral neuropathy, mood/CNS changes) and refractory nausea/vomiting are the practical limits to therapy; pyridoxine has been studied for neurotoxicity. Renal effects are a minor part of the safety profile.

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Clinical depth

Renal dose adjustment

No established renal-specific dosing algorithm; altretamine is extensively hepatically metabolized with low urinary excretion of unchanged drug. Dose reductions and interruptions are primarily for GI, neurologic and hematologic toxicity.

Dialyzability & ESKD dosing

Not characterized as dialyzable; high lipid solubility, extensive hepatic metabolism and tissue distribution make significant dialytic removal unlikely. Dialysis is not used for drug clearance.

Differential diagnosis

Distinguish mild altretamine-associated creatinine rise from cisplatin nephrotoxicity, prerenal azotemia due to vomiting, and obstruction by pelvic/ovarian disease. True intrinsic altretamine nephrotoxicity is mild and not well established as an independent entity.

Monitoring

Neurologic examination for peripheral/central neurotoxicity
CBC for myelosuppression
Assessment of nausea/vomiting and volume status

Key trials & series

Phase II single-agent altretamine trials in recurrent/platinum-pretreated ovarian cancer (response rates ~14-33%), summarized in pharmacologic reviews (PMID 7641606, PMID 1905441)

Clinical pearls

Aggressive antiemesis and hydration prevent the most likely renal problem, prerenal volume depletion from vomiting.

Where it strikes· nephron segments & injury signatures

Nephron segments

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Injury signatures

Prerenal / Hemodynamic AKI

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

Class-level context for the major non-renal toxicities of the Alkylating agent (methylmelamine) class.

Ophthalmic

Keratopathy, uveitis, retinopathy

Visual disturbance (crizotinib)

Hepatic / Liver

Transaminitis, hepatitis, VOD/SOS

Transaminitis

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

CNS effects (lorlatinib)

§05

References

3 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

3 references · 1991–2017 · 1 since 2015

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.

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 Altretamine (hexamethylmelamine) 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

Dacarbazine

DTIC · Alkylator

Profile

Rare hepatic veno-occlusive disease; minimal direct renal injury.

PRE

Mild#1 · 77% phenotype match

Estramustine

Emcyt · Hormonal–alkylating conjugate

Profile

Fluid retention, edema and thromboembolism.

PRE

Mild#2 · 76% phenotype match

Bleomycin

Blenoxane · Antitumor antibiotic

Profile

Renally excreted (~2/3 in urine); half-life rises exponentially below CrCl 25-35 — exposure/clearance issue amplifying pulmonary toxicity, not a direct nephrotoxin.

PRE

Mild#3 · 76% phenotype match

Asparaginase

Elspar · Enzyme

Profile

Rare AKI; pancreatitis-mediated.

PRE

Mild#4 · 66% phenotype match

Belzutifan

Welireg · HIF-2α inhibitor

Profile

Anemia/hypoxia; emerging renal profile in VHL/RCC.

PRE

Mild#5 · 66% phenotype match

Eribulin

Halaven · Microtubule inhibitor

Profile

Reduced clearance in renal impairment.

PRE

Mild#6 · 66% phenotype match

Compare Altretamine (hexamethylmelamine) 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.