What kind of kidney injury does Binimetinib cause?

Acute Tubular Necrosis — Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate. Other reported patterns: Prerenal / Hemodynamic AKI.

Is kidney injury from Binimetinib reversible?

Reversible. Typical onset: Weeks into therapy..

How should kidney function be monitored during Binimetinib therapy?

Creatine phosphokinase at baseline and periodically; immediately with myalgia or dark urine; LVEF and ophthalmologic assessment per label; Serum creatinine at baseline and periodically.

Who is at higher risk of kidney injury from Binimetinib?

Strenuous activity / statin co-use (CK); Volume depletion; Pre-existing CKD.

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Printable monograph

MEK inhibitor

Binimetinib

Mektovi · Bini

MEK inhibitor · approved 2018 · 9 citations · FAERS AKI reporting ROR 3.19 (95% CI 2.75–3.71, 177 AKI reports)

Aging evidence· through 2022

Fairly sourced4/9 · 4 signals

Met: 9 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 5y)
Not met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2022
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 whose renal signal is a modest creatinine rise — with rare rhabdomyolysis reports.

MildMEK inhibitor

BRAF V600-mutant melanoma (with encorafenib)

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

Clinically significant intrinsic nephrotoxicity is uncommon; modest creatinine elevations occur and CK elevation is a recognized MEK-class effect. In COLUMBUS, grade 3-4 blood-CK increase occurred in ~7% with encorafenib plus binimetinib; rare rhabdomyolysis can secondarily threaten the kidney.Source: Dummer et al., Lancet Oncol 2018 (COLUMBUS)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Weeks into therapy.

Distilled from: “Weeks into 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.

Acute Tubular Necrosis#1 · Signaturequalitative — no citable incidence
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

§03

Kidney injury

Deep diveBRAF/MEK-inhibitor tubular injuryVemurafenib was built to block a mutated melanoma kinase, but in the kidney its damage is off-target: it injures the proximal tubule and can produce a Fanconi picture, usually early and usually mild — and, paradoxically, pairing it with a MEK inhibitor makes it gentler on the kidney, not harsher.

Mechanism of kidney injury

Direct nephrotoxicity is not characteristic; modest creatinine changes occur within the BRAF/MEK class (partly transporter-mediated). MEK inhibitors are associated with asymptomatic CK elevation and, rarely, rhabdomyolysis, which can cause pigment (myoglobin) cast nephropathy and proximal tubular injury.

Clinical presentation

Usually mild creatinine rise; watch for myalgia, marked CK elevation and, rarely, rhabdomyolysis with pigment nephropathy (tea-colored urine, dipstick blood without RBCs, AKI). Peripheral edema and LV dysfunction are other class effects to track.

Management

Hold drug for marked CK rise/rhabdomyolysis; aggressive IV crystalloid for pigment nephropathy with goal urine output; supportive AKI care, and resume only after CK and renal function normalize.Lesion-level management framework

Risk factors

Strenuous activity / statin co-use (CK)
Volume depletion
Pre-existing CKD

Anticancer mechanism· how it treats cancer

Selective, reversible MEK1/2 inhibitor blocking MAPK signaling; given with encorafenib in BRAF V600-mutant melanoma.

§04

Clinical depth

Renal dose adjustment

No dedicated renal dose adjustment; no change recommended for mild-moderate impairment, and severe impairment/dialysis are not studied. Modifications are driven by CK, LVEF, retinopathy, and hepatic toxicity.

Dialyzability & ESKD dosing

Highly protein-bound oral small molecule; not expected to be appreciably dialyzed. No validated ESKD dosing.

Differential diagnosis

Rhabdomyolysis-associated pigment nephropathy (elevated CK, positive urine heme without RBCs, brown granular casts) vs transporter-mediated pseudo-creatinine rise vs prerenal AKI. The CK level and urinalysis quickly separate these.

Monitoring

Creatine phosphokinase at baseline and periodically; immediately with myalgia or dark urine
LVEF and ophthalmologic assessment per label
Serum creatinine at baseline and periodically

Key trials & series

COLUMBUS (encorafenib + binimetinib in BRAF-mutant melanoma)
Sanagawa 2021 real-world BRAF/MEK nephrotoxicity analysis

Clinical pearls

A rising creatinine with myalgia on binimetinib should trigger an immediate CK to catch rhabdomyolysis.
Most of the renal risk is indirect (rare rhabdomyolysis); de novo intrinsic nephrotoxicity is low.
Pigment nephropathy is managed with early, generous IV fluids — do not wait for oliguria.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Injury signatures

Prerenal / Hemodynamic AKI Acute Tubular Necrosis

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

6 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

6 references · 2018–2022 · 4 since 2020

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· 3

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.

CaseB · ModerateGlomerulonephritis and granulomatous vasculitis in kidney as a complication of the use of BRAF and MEK inhibitors in the treatment of metastatic melanoma: A case report.Maanaoui M et al. · Medicine (Baltimore) 2017 · PMID 28640105Biopsy-proven glomerulonephritis with renal granulomatous vasculitis and proteinuria in a patient treated with encorafenib and binimetinib, resolving after drug withdrawal.CaseC · LimitedTubulointerstitial Nephritis in an Advanced Melanoma Patient Treated with Encorafenib plus Binimetinib Combination Therapy.Kambayashi Y et al. · Case Rep Oncol 2022 · PMID 35702675Case report of tubulointerstitial nephritis developing in a melanoma patient on encorafenib plus binimetinib combination therapy.CaseC · LimitedAcute renal failure under encorafenib, binimetinib and cetuximab for BRAF V600E-mutated colorectal cancer.Stammler R et al. · Eur J Cancer 2021 · PMID 33618199Case report of acute renal failure (AKI) developing under encorafenib/binimetinib/cetuximab therapy for BRAF V600E-mutated colorectal cancer.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 7,756 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· 3 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

Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
Acute Tubular NecrosisNot measurable in reporting — Reporters cannot reliably name this lesion, so its absence from FAERS is expected and is not evidence against the documented injury.

Acute Interstitial Nephritis

ROR 2.1795% CI 1.31–3.60· 15 reports

SIADH / Hyponatremia

ROR 1.9595% CI 1.51–2.53· 58 reports

Electrolyte Disturbance

ROR 1.8395% CI 1.53–2.17· 128 reports

FAERS outcomes & reporting trend· 15.6% of reports w/ death · 29.1% w/ hospitalization

15.6%

Reported with a death outcome

1,209 of 7,756 reports

29.1%

Reported with hospitalization

2,258 of 7,756 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 10 systems · 7,756 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 3.1995% CI 2.75–3.71· 177 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 Injury177

Gastrointestinal

Nausea715Diarrhoea570Vomiting415Constipation174Abdominal Pain139

General / constitutional

Fatigue604Pyrexia542Malaise225Asthenia170Pain155

Skin

Rash397

Eye

Vision Blurred212Visual Impairment180

Musculoskeletal

Arthralgia229Myalgia134

Metabolic & electrolyte

Decreased Appetite225

Blood & lymphatic

Anaemia150

Nervous system

Headache145

Respiratory

Dyspnoea136

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 Binimetinib 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

Sotorasib

Lumakras · KRAS G12C inhibitor

Profile

Newer agent; renal data emerging.

PREATN

Mild#1 · 89% phenotype match

Pegaspargase

Oncaspar · Enzyme (asparaginase)

Profile

Rare AKI; pancreatitis- and thrombosis-mediated.

PREATN

Mild#2 · 89% phenotype match

Tretinoin (ATRA)

Vesanoid · Retinoid (differentiating agent)

Profile

Differentiation syndrome → capillary leak and AKI.

PREATN

Moderate#3 · 84% phenotype match

Tagraxofusp

Elzonris · IL-3 immunotoxin

Profile

Capillary-leak syndrome → AKI.

PREATN

Moderate#4 · 84% phenotype match

Talquetamab

Talvey · Bispecific (GPRC5D×CD3)

Profile

CRS-related AKI — emerging.

PREATN

Moderate#5 · 84% phenotype match

Teclistamab

Tecvayli · Bispecific (BCMA×CD3)

Profile

CRS-associated AKI in myeloma — emerging signal.

PREATN

Moderate#6 · 84% phenotype match

Compare Binimetinib 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.