What kind of kidney injury does Mechlorethamine cause?

Electrolyte Disturbance — Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia). Other reported patterns: Crystal / Obstructive Nephropathy.

Is kidney injury from Mechlorethamine reversible?

Reversible. Typical onset: TLS within hours to days of effective cytoreduction in bulky lymphoma..

How should kidney function be monitored during Mechlorethamine therapy?

Serum creatinine, potassium, phosphate, calcium and uric acid during initial cytoreduction; (Topical) local skin reactions rather than renal labs.

How can kidney injury from Mechlorethamine be prevented?

TLS risk stratification before treating bulky disease IV hydration Allopurinol or rasburicase per risk Prefer topical route for limited cutaneous disease where systemic exposure is unnecessary

Who is at higher risk of kidney injury from Mechlorethamine?

High tumor burden / bulky chemosensitive lymphoma; Elevated baseline uric acid or LDH; Volume depletion and pre-existing CKD; Inadequate hydration or uric-acid prophylaxis.

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Printable monograph

Alkylating agent (nitrogen mustard)

Mechlorethamine

Mustargen · MECH

Alkylating agent (nitrogen mustard) · approved 1949 · 4 citations

Aging evidence· through 2021

Fairly sourced5/9 · 4 signals

Not met: 4 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 10y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2021
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.

Prototype nitrogen mustard alkylator whose renal relevance is tumor lysis in bulky lymphoma; the modern topical gel has no detectable systemic absorption.

Moderateearly-cytotoxic

Hodgkin lymphoma (historically as the M in MOPP)Non-Hodgkin lymphomaMycosis fungoides / cutaneous T-cell lymphoma (topical gel)Malignant pleural and pericardial effusions (intracavitary, historical)

§01

Signature kidney injury

Signature lesion

Electrolyte Disturbance

Direct nephrotoxicity is not a defining feature. The principal renal hazard is tumor lysis syndrome when treating bulky, rapidly proliferating lymphoma; incidence specifically attributable to mechlorethamine is not quantified because it is used within multi-agent regimens. The 0.016%/0.02% topical gel shows no detectable systemic absorption.Source: Lessin et al., JAMA Dermatol 2013 (topical gel: no detectable systemic absorption)

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Tumor-lysis AKI within hours to days of effective cytoreduction in bulky lymphoma.

Distilled from: “TLS within hours to days of effective cytoreduction in bulky lymphoma.”

§02

Renal toxicities, ranked

This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Electrolyte Disturbance#1 · Signaturequalitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
Crystal / Obstructive NephropathySecondaryqualitative — no citable incidence
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.

§03

Kidney injury

Mechanism of kidney injury

As a class alkylator, systemic mechlorethamine can contribute to tumor lysis in chemosensitive bulky disease, with uric-acid and phosphate intratubular precipitation and AKI. A direct tubular (ATN-type) insult is conceivable for a highly reactive alkylating agent but is not a well-characterized clinical signature. Topically applied gel does not reach the systemic circulation in measurable amounts, so renal exposure is negligible.

Clinical presentation

When TLS occurs, hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia and rising creatinine shortly after starting therapy. No characteristic urinary syndrome is attributed to the drug itself; topical use is associated with skin irritation rather than kidney effects.

Management

Treat TLS with hydration, uric-acid-lowering therapy, electrolyte correction and dialysis if refractory. No specific antidote exists for mechlorethamine renal effects; supportive care and hydration are the mainstays. Topical exposures require only local skin care.Lesion-level management framework

Risk factors

High tumor burden / bulky chemosensitive lymphoma
Elevated baseline uric acid or LDH
Volume depletion and pre-existing CKD
Inadequate hydration or uric-acid prophylaxis

Prevention

TLS risk stratification before treating bulky disease
IV hydration
Allopurinol or rasburicase per risk
Prefer topical route for limited cutaneous disease where systemic exposure is unnecessary

Anticancer mechanism· how it treats cancer

Highly reactive bifunctional nitrogen mustard that forms an aziridinium ion and crosslinks DNA (predominantly at the N7 of guanine), producing interstrand and intrastrand crosslinks that block replication and trigger apoptosis.

Note · Systemic mechlorethamine is largely of historical interest (MOPP), now supplanted by ABVD and other regimens; the contemporary product in wide use is the topical gel for mycosis fungoides, which carries negligible systemic/renal risk.

§04

Clinical depth

Renal dose adjustment

No validated renal dose-adjustment algorithm for systemic use; the drug is rapidly chemically hydrolyzed with very short plasma half-life. Topical gel requires no renal adjustment given absent systemic absorption.

Dialyzability & ESKD dosing

Not relevant for drug removal given near-instantaneous chemical degradation in plasma; dialysis is used only to manage TLS metabolic complications.

Differential diagnosis

Distinguish TLS-driven AKI from prerenal azotemia and from obstruction by bulky nodal disease. Direct alkylator tubular injury is not a well-established clinical entity for this drug and should be a diagnosis of exclusion.

Monitoring

Serum creatinine, potassium, phosphate, calcium and uric acid during initial cytoreduction
(Topical) local skin reactions rather than renal labs

Key trials & series

MOPP-era Hodgkin lymphoma regimens establishing mechlorethamine as a systemic alkylator (regimen-level evidence)
Randomized multicenter trial of mechlorethamine 0.02% gel in mycosis fungoides demonstrating efficacy with no detectable systemic absorption (PMID 23069814)

Clinical pearls

Hydration and uric-acid prophylaxis remain the key kidney-protective steps when treating bulky chemosensitive disease.

Where it strikes· nephron segments & injury signatures

Nephron segments

Tubular Lumen

The urine flow path

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Injury signatures

Electrolyte Disturbance Crystal / Obstructive Nephropathy

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

Class-level context for the major non-renal toxicities of the Alkylating agent (nitrogen mustard) 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

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

Evidence accrual

4 references · 2011–2021 · 2 since 2019

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.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 2,244 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.

FAERS outcomes & reporting trend· 6.9% of reports w/ death · 11.1% w/ hospitalization

6.9%

Reported with a death outcome

154 of 2,244 reports

11.1%

Reported with hospitalization

248 of 2,244 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 2 systems · 2,244 reports

Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 0.0695% CI 0.01–0.43· 1 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

Skin

Pruritus322Application Site Pruritus224Application Site Erythema220Erythema213Skin Discolouration147

General / constitutional

Application Site Pain218Fatigue55Pain52

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 Mechlorethamine 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

Amsacrine

Amsidine · Topoisomerase II inhibitor (acridine)

Profile

Predominantly hepatobiliary elimination; renal clearance minor, kidney risk mainly tumor lysis in AML; reduce dose in organ impairment.

LYTEXTAL

Moderate#1 · 86% phenotype match

Lurbinectedin

Zepzelca · Marine alkylating agent

Profile

Rhabdomyolysis risk in small-cell lung cancer.

ATNLYTEXTAL

Mild#2 · 72% phenotype match

Infigratinib

Truseltiq · FGFR inhibitor

Profile

Hyperphosphatemia — on-target FGFR class effect; nephrocalcinosis risk.

LYTEXTAL

Moderate#3 · 71% phenotype match

Bendamustine

Treanda · Alkylator

Profile

Tumor lysis-mediated AKI is the principal risk; TMA is rare.

XTALTMALYTE

Moderate#4 · 65% phenotype match

Trabectedin

Yondelis · Marine alkylating agent

Profile

Rhabdomyolysis → pigment nephropathy; hepatotoxicity.

ATNLYTE

Moderate#5 · 62% phenotype match

Dactinomycin (actinomycin D)

Cosmegen · Antitumor antibiotic

Profile

Renal risk indirect via tumor lysis in chemosensitive pediatric tumors; hepatic veno-occlusive disease is the signature organ toxicity.

LYTEPREXTAL

Moderate#6 · 56% phenotype match

Compare Mechlorethamine 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.