What kind of kidney injury does Mirdametinib cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome. Other reported patterns: Electrolyte Disturbance.

How should kidney function be monitored during Mirdametinib therapy?

Weight and edema assessment each visit; LVEF (echo) and ophthalmologic exam per MEK-inhibitor label; CK if muscle symptoms; Serum creatinine and electrolytes on therapy.

How can kidney injury from Mirdametinib be prevented?

Manage diarrhea and maintain hydration

Who is at higher risk of kidney injury from Mirdametinib?

Significant treatment-related diarrhea or edema; Baseline cardiac/renal impairment; Concurrent nephrotoxins or diuretics.

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Printable monograph

MEK inhibitor

Mirdametinib

Gomekli · MIRD

MEK inhibitor · approved 2025 · 4 citations

Recent· through 2024

Fairly sourced4/9 · 4 signals

Not met: 4 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 9y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2024
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.

A MEK inhibitor for NF1 plexiform neurofibromas whose renal footprint is edema and modest creatinine shifts.

MildMEK inhibitor

NF1-associated plexiform neurofibromas (adult and pediatric)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

No established intrinsic nephrotoxicity. Across MEK-inhibitor experience (including the NF106 mirdametinib trial) the characteristic toxicities are rash, edema, diarrhea and CK elevation; renal events are not a defining signal and any creatinine change is qualitative rather than a quantified AKI rate.Source: Weiss et al., J Clin Oncol 2021

Onset & rechallenge

Time to injuryVariable / unpredictable

Not well defined; edema and any creatinine changes evolve during ongoing therapy.

Distilled from: “Not well defined; edema and any creatinine changes evolve during ongoing therapy.”

§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.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Electrolyte DisturbanceSecondaryqualitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

§03

Kidney injury

Mechanism of kidney injury

No characterized direct nephron injury. MEK inhibitors commonly cause peripheral edema and fluid retention and can produce hemodynamic shifts; a mild creatinine rise, if seen, is most consistent with prerenal/edema-related changes or diarrhea-driven GI volume loss rather than tubular damage. Class-associated rhabdomyolysis from marked CK elevation is a rare theoretical route to myoglobinuric AKI.

Clinical presentation

Peripheral/periorbital edema and weight gain; if present, a modest reversible creatinine increase with bland sediment; electrolytes generally track GI losses if diarrhea is prominent. Marked CK rise warrants checking for muscle injury.

Management

Supportive: manage edema and diarrhea, ensure euvolemia, and interrupt/reduce dose per protocol for significant toxicity. Intrinsic renal injury has not been characterized; evaluate alternative causes before attributing AKI to the drug.Lesion-level management framework

Risk factors

Significant treatment-related diarrhea or edema
Baseline cardiac/renal impairment
Concurrent nephrotoxins or diuretics

Prevention

Manage diarrhea and maintain hydration

Anticancer mechanism· how it treats cancer

Oral allosteric MEK1/2 inhibitor that blocks downstream MAPK/ERK signaling, shrinking neurofibromas in the constitutively active RAS/MAPK setting of neurofibromatosis type 1 (NF1, with loss of the RAS-GAP neurofibromin). Approved for adults and children with NF1-associated symptomatic, inoperable plexiform neurofibromas.

Note · 2025 approval with minimal renal-specific data; the cited NF106 trial used the same agent (PD-0325901) in NF1 PN. Prerenal/edema framing is conservative MEK-class reasoning, not a quantified renal signal.

§04

Clinical depth

Renal dose adjustment

No established renal dose adjustment; mirdametinib is hepatically metabolized with low renal elimination, so reduced GFR is not expected to require modification. Dosing is BSA-based in children. No data in severe impairment or dialysis.

Dialyzability & ESKD dosing

Not characterized; a small, protein-bound, non-renally cleared molecule is unlikely to be appreciably dialyzed. No ESKD dosing guidance.

Differential diagnosis

Distinguish edema/prerenal creatinine change (volume redistribution, responds to diuresis/euvolemia) from rare rhabdomyolysis-associated AKI (very high CK, pigmented sediment); structural MEK-inhibitor nephrotoxicity is not described.

Monitoring

Weight and edema assessment each visit
LVEF (echo) and ophthalmologic exam per MEK-inhibitor label
CK if muscle symptoms
Serum creatinine and electrolytes on therapy

Key trials & series

NF106 (Weiss, JCO 2021) — mirdametinib NF1 plexiform-neurofibroma trial
ReNeu — registrational adult/pediatric NF1-PN study supporting 2025 approval

Clinical pearls

Edema is the signature MEK-inhibitor effect — a small creatinine bump usually reflects fluid shifts, not tubular injury.
Track CK: marked elevation is the one route to true (myoglobinuric) AKI in this class.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Prerenal / Hemodynamic AKI Electrolyte Disturbance

Beyond the kidney — non-renal toxicities· 4 organ systems

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

Dermatologic

Rash, HFS, SJS/TEN, vitiligo

Rash, photosensitivity, squamous-cell carcinomas (BRAF)

Cardiac

Cardiomyopathy, QT, ischemia, myocarditis

Reduced LVEF (MEK)

Ophthalmic

Keratopathy, uveitis, retinopathy

Retinopathy / retinal vein occlusion (MEK)

Vascular

Hypertension, VTE/ATE, bleeding, aneurysm

Pyrexia syndrome, hypertension

§05

References

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

Evidence accrual

4 references · 2015–2024 · 2 since 2022

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· 13

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.

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 Mirdametinib 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

Imetelstat

Rytelo · Telomerase inhibitor

Profile

2024 MDS agent; tumor lysis risk.

PRELYTE

Mild#1 · 89% phenotype match

Zanidatamab

Ziihera · HER2 bispecific antibody

Profile

2024 biliary-tract HER2 bispecific; renal data emerging.

PRELYTE

Mild#2 · 89% phenotype match

Zenocutuzumab

Bizengri · HER2×HER3 bispecific antibody

Profile

2024 NRG1-fusion bispecific; mostly grade 1-2 AEs — at most diarrhea-related prerenal risk, no CRS/TLS mechanism.

PRELYTE

Mild#3 · 89% phenotype match

Quizartinib

Vanflyta · FLT3 inhibitor

Profile

2023 AML FLT3 inhibitor; tumor lysis and QT.

PRELYTE

Mild#4 · 89% phenotype match

Avapritinib

Ayvakit · KIT / PDGFRA inhibitor

Profile

Edema, intracranial bleeding and cognitive effects.

PRELYTE

Mild#5 · 89% phenotype match

Daratumumab

Darzalex · Anti-CD38 antibody

Profile

Tumor lysis; usable in renal impairment.

PRELYTE

Mild#6 · 86% phenotype match

Compare Mirdametinib 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 BRAF / MEK inhibitors

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.