What kind of kidney injury does Melphalan cause?

SIADH / Hyponatremia — Inappropriate water retention at the collecting duct — high-dose cyclophosphamide. Other reported patterns: Electrolyte Disturbance.

Is kidney injury from Melphalan reversible?

Reversible. Typical onset: Days after high-dose administration..

How should kidney function be monitored during Melphalan therapy?

Serum sodium and fluid balance during/after high-dose therapy; Mucositis severity and volume status (diarrhea-related hyponatremia).

How can kidney injury from Melphalan be prevented?

Avoid excess hypotonic fluids Dose-reduce (e.g., 140 mg/m2) and monitor in renal impairment / amyloidosis

Who is at higher risk of kidney injury from Melphalan?

High-dose / bolus IV administration (conditioning); Renal impairment (reduced clearance, greater mucosal toxicity); Concurrent hypotonic fluids; Mucositis/diarrhea-related volume loss.

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Printable monograph

Alkylator

Melphalan

Alkeran · Mel

Alkylator · approved 1964 · 8 citations · FAERS AKI reporting ROR 3.30 (95% CI 3.04–3.58, 586 AKI reports)

Up to date· through 2025

Deeply sourced8/9 · 7 signals

Met: 8 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 40y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
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.

The myeloma workhorse whose high-dose conditioning can quietly drop the serum sodium.

MildAlkylator

Multiple myelomaAutologous stem cell transplant conditioningLight-chain (AL) amyloidosisOvarian cancer; regional perfusion for melanoma

§01

Signature kidney injury

Signature lesion

SIADH / Hyponatremia

High-dose intravenous melphalan can cause hyponatremia/SIADH; in a small high-dose series most patients showed declining sodium, but this is reported at case/series level rather than as a large quantified rate. Melphalan PK is not adversely affected by renal failure, so transplant in renal impairment is feasible.Source: Greenbaum-Lefkoe et al., Cancer 1985

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Days after high-dose administration.

Distilled from: “Days after high-dose administration.”

§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.

SIADH / Hyponatremia#1 · Signatureno population incidence denominator
SIADH with hyponatremia and inappropriate urinary sodium loss reported after high-dose IV bolus melphalan (both patients at 2 mg/kg; falling serum Na in 7/10 at 1 mg/kg). PMID 3965085 (opens PubMed in a new tab)
Electrolyte DisturbanceSecondary35%PMID 3153241 (opens PubMed in a new tab)
Hyponatremia in 12/34 (35%) after high-dose melphalan, coinciding with diarrhea ~day 10-12 (attributed to GI losses, not SIADH).

§03

Kidney injury

Deep diveDrug-induced SIADH: the sodium falls and the tumour takes the blameHyponatremia is the commonest electrolyte disorder in oncology and its commonest explanation is the cancer itself — which is exactly why a drug that impairs free-water excretion can go on being given for months while the sodium is treated as a feature of the disease.

Mechanism of kidney injury

High-dose bolus melphalan can precipitate inappropriate antidiuretic hormone secretion with free-water retention and dilutional hyponatremia; conditioning-related mucositis and diarrhea cause additional volume and sodium disturbances (some hyponatremia is GI-loss rather than true SIADH). Melphalan is partly renally cleared, so impaired kidney function raises systemic and mucosal toxicity and motivates dose reduction (e.g., 200 to 140 mg/m2) in renal failure/amyloidosis.

Clinical presentation

Hyponatremia with inappropriately concentrated urine and ongoing natriuresis (SIADH pattern); in the conditioning setting, accompanying mucositis, diarrhea and volume shifts. Direct tubular nephrotoxicity is not characteristic.

Management

Manage SIADH with fluid restriction and careful, rate-limited sodium correction; treat volume and electrolyte derangements supportively. Hyponatremia typically resolves as the acute effect and mucositis abate.Lesion-level management framework

Risk factors

High-dose / bolus IV administration (conditioning)
Renal impairment (reduced clearance, greater mucosal toxicity)
Concurrent hypotonic fluids
Mucositis/diarrhea-related volume loss

Prevention

Avoid excess hypotonic fluids
Dose-reduce (e.g., 140 mg/m2) and monitor in renal impairment / amyloidosis

Anticancer mechanism· how it treats cancer

Phenylalanine-mustard bifunctional alkylating agent that cross-links DNA. Backbone of multiple myeloma therapy and the standard high-dose conditioning agent before autologous stem cell transplant; also used in light-chain (AL) amyloidosis and (regional perfusion) melanoma.

§04

Clinical depth

Renal dose adjustment

For high-dose conditioning, 140 mg/m2 is commonly used as a conservative dose in significant renal impairment / dialysis dependence and in AL amyloidosis. Melphalan pharmacokinetics are NOT adversely affected by impaired renal function (Tricot), so renal impairment is not itself a barrier to high-dose conditioning; that study nonetheless found renal insufficiency associated with longer fever and hospitalization, and the same group later reported that the more pronounced toxicity of the 200 mg/m2 regimen is why 140 mg/m2 became the standard of care.

Dialyzability & ESKD dosing

Melphalan is short-lived (rapid chemical hydrolysis) so it is not reliably removed by dialysis as a rescue; however, high-dose autotransplant has been performed safely in dialysis-dependent patients using the reduced 140 mg/m2 dose with attention to mucositis.

Differential diagnosis

Euvolemic hyponatremia with concentrated urine and natriuresis points to SIADH; hypovolemic hyponatremia with low urine sodium and clinical volume loss points to mucositis/diarrhea-driven depletion. The distinction changes management (fluid restriction vs cautious repletion).

Monitoring

Serum sodium and fluid balance during/after high-dose therapy
Mucositis severity and volume status (diarrhea-related hyponatremia)

Key trials & series

Greenbaum-Lefkoe Cancer 1985 - original SIADH/hyponatremia description after high-dose IV melphalan
Tricot Clin Cancer Res 1996 - PK/toxicity of high-dose melphalan autotransplant in renal failure
Sanchorawala Bone Marrow Transplant 2001 - HDM/SCT in AL amyloidosis with renal involvement

Clinical pearls

Check sodium after high-dose melphalan - SIADH is the signature renal-electrolyte event, not tubular injury.
Renal failure is NOT a contraindication to high-dose melphalan transplant; reduce to 140 mg/m2 and watch mucositis.
Not all post-conditioning hyponatremia is SIADH - GI losses from mucositis/diarrhea are a common, differently managed cause.

Where it strikes· nephron segments & injury signatures

Nephron segments

Distal Tubule / Collecting Duct

Fine-tuning of Na, K, Mg, acid & water

Injury signatures

SIADH / Hyponatremia Electrolyte Disturbance

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

Class-level context for the major non-renal toxicities of the Alkylator class.

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

§05

References

7 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

7 references · 1985–2007 · 1 since 2005

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.

Case reports — ranked by strength· 1

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseC · LimitedTransplant-Associated Thrombotic Microangiopathy After Autologous Hematopoietic Stem Cell Transplantation Treated With Eculizumab.Tokura T et al. · Cureus 2025 · PMID 40717883An adult developed transplant-associated thrombotic microangiopathy with new-onset hypertension, microangiopathic hemolytic anemia, thrombocytopenia, and renal failure after autologous HSCT conditioned with the melphalan-containing MEAM regimen, implicating high-dose melphalan conditioning in the TMA-associated acute kidney injury.

FDA label — boxed warning & renal dosing· boxed warning

Quoted verbatim from this agent's current FDA label (Jul 2026) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

BOXED WARNING Melphalan should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Severe bone marrow suppression with resulting infection or bleeding may occur. Controlled trials comparing intravenous (IV) to oral melphalan have shown more myelosuppression with the IV formulation. Hypersensitivity reactions, including anaphylaxis, have occurred in approximately 2% of patients who received the IV formulation. Melphalan is leukemogenic in humans. Melphalan produces chromosomal aberrations in vitro and in vivo and, therefore, should be considered potentially mutagenic in humans.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 24,928 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.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
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 reported renal phenotypes· 8 signals

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Electrolyte Disturbancecorroborated · ROR 2.13 — on the terms that name the lesion (ROR 2.07)
SIADH / Hyponatremiacorroborated · ROR 1.95 — on the terms that name the lesion (ROR 4.66)

Thrombotic Microangiopathy

ROR 29.3995% CI 26.89–32.12· 513 reports

Hemorrhagic Cystitis

ROR 3.2495% CI 2.87–3.65· 264 reports

Fanconi Syndrome

ROR 3.1395% CI 1.99–4.91· 19 reports

Acute Interstitial Nephritis

ROR 2.7995% CI 2.18–3.59· 62 reports

Glomerular Injury / Proteinuria

ROR 2.3895% CI 1.92–2.96· 82 reports

Electrolyte Disturbance

ROR 2.1395% CI 1.94–2.33· 478 reports

Acute Tubular Necrosis

ROR 1.9795% CI 1.31–2.97· 23 reports

SIADH / Hyponatremia

ROR 1.9595% CI 1.69–2.25· 186 reports

FAERS outcomes & reporting trend· 23.8% of reports w/ death · 28.8% w/ hospitalization

23.8%

Reported with a death outcome

5,943 of 24,928 reports

28.8%

Reported with hospitalization

7,187 of 24,928 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 24,928 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 3.3095% CI 3.04–3.58· 586 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Renal & urinary

Acute Kidney Injury586Renal Failure488

Blood & lymphatic

Febrile Neutropenia1,317Neutropenia1,234Thrombocytopenia1,143Anaemia750Pancytopenia675

Immune / infection

Pneumonia1,152Sepsis900Infection764Acute Graft Versus Host Disease575Graft Versus Host Disease507

Gastrointestinal

Mucosal Inflammation1,229Diarrhoea1,044Nausea595

General / constitutional

Pyrexia1,175

Nervous system

Neuropathy Peripheral750

Hepatobiliary

Venoocclusive Liver Disease544

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 Melphalan 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

Temozolomide

Temodar · Alkylator

Profile

Occasional SIADH; generally renally well tolerated.

SIADHLYTE

Mild#1 · 100% phenotype match

Chlorambucil

Leukeran · Alkylating agent (nitrogen mustard)

Profile

Minimal direct nephrotoxicity; rare drug-associated SIADH/hyponatremia is the kidney-relevant signal.

SIADHLYTE

Mild#2 · 97% phenotype match

Vinblastine

Velban · Vinca alkaloid

Profile

SIADH and rare Raynaud/vascular events.

SIADHLYTE

Mild#3 · 89% phenotype match

Vincristine

Oncovin · Vinca alkaloid

Profile

SIADH → hyponatremia.

SIADHLYTE

Mild#4 · 89% phenotype match

Vinorelbine

Navelbine · Vinca alkaloid

Profile

SIADH reports.

SIADHLYTE

Mild#5 · 89% phenotype match

Vismodegib

Erivedge · Hedgehog (SMO) inhibitor

Profile

Muscle spasms; hyponatremia reported.

SIADHLYTE

Mild#6 · 87% phenotype match

Compare Melphalan 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.

Who studies this

The leading contributors to Melphalan’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Melphalan; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 169 clinical records among the 300 most-relevant of 398 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.