What kind of kidney injury does BRAF / MEK Inhibitors cause?

Acute Tubular Necrosis — Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate. Other reported patterns: Acute Interstitial Nephritis, Electrolyte Disturbance, Pseudo-AKI, Fanconi Syndrome.

Is kidney injury from BRAF / MEK Inhibitors reversible?

Reversible. Typical onset: Acute–subacute during therapy..

How should kidney function be monitored during BRAF / MEK Inhibitors therapy?

Baseline and serial creatinine/eGFR — vemurafenib in particular causes a reversible creatinine rise (partly tubular-secretion blockade, partly true AKI), so trend it rather than react to a single value.; Basic metabolic panel for electrolytes — watch for hypophosphatemia/hypokalemia and a Fanconi-type proximal tubular pattern reported with vemurafenib; check magnesium given concurrent GI losses.; During any drug-induced pyrexia (especially dabrafenib/trametinib), check renal function and volume status promptly — febrile dehydration is the dominant route to prerenal AKI/ATN in this class.; Reassess creatinine after holding/resuming or down-titrating for febrile or GI toxicity; most creatinine elevations recover, supporting the reversible class profile.; If a MEK inhibitor causes peripheral edema/fluid retention, distinguish hemodynamic creatinine shifts from structural injury before attributing AKI to the drug..

How can kidney injury from BRAF / MEK Inhibitors be prevented?

Rehydrate and treat drug-induced pyrexia early (especially on dabrafenib + trametinib) — febrile dehydration is the dominant route to AKI in this class Replete phosphate, potassium and magnesium for the vemurafenib Fanconi-type proximal tubular pattern

Who is at higher risk of kidney injury from BRAF / MEK Inhibitors?

Vemurafenib (vs dabrafenib); Volume depletion; Concurrent nephrotoxins.

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Printable monograph

BRAF/MEK inhibitor

BRAF / MEK Inhibitors

Zelboraf · Tafinlar · Mekinist · BRAF/MEK

BRAF/MEK inhibitor · approved 2011 · 8 citations

Aging evidence· through 2022

Thinly sourced3/9 · 3 signals

Met: 8 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 9y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
Met: Landmark reference
Not met: Current through 2022
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.

Mild but real — vemurafenib carries the strongest tubular signal of the class.

MildMAPK-pathway targeted therapy

BRAF-mutant melanomaNSCLCThyroid

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

Representative incidence21%

Pharmacovigilance shows vemurafenib > dabrafenib. Mild creatinine elevation common, serious AKI uncommon. Reported rate: acute kidney injury in 21% — 199 patients who received dabrafenib/trametinib in a single large US healthcare system between 2010 and 2019… (Seethapathy 2022, PMID 33355659).Source: Seethapathy et al., Nephrol Dial Transplant 2022

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Acute-to-subacute creatinine rise during therapy.

Distilled from: “Acute–subacute during 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 · Signatureno population incidence denominator
Tubular/tubulointerstitial injury is the documented mode of BRAF-inhibitor AKI; FAERS captured 132 vemurafenib and 13 dabrafenib acute kidney injury reports (2011-2014), with vemurafenib apparently more nephrotoxic and injury more common in men. PMID 26182194 (opens PubMed in a new tab)
Electrolyte DisturbanceSecondaryno population incidence denominator
Hyponatremia (8 vemurafenib, 6 dabrafenib) and hypokalemia (6 and 2) accompanied the AKI reports in the FAERS analysis; electrolyte monitoring is advised with these agents. PMID 26182194 (opens PubMed in a new tab)
Acute Interstitial NephritisRarequalitative — no citable incidence
Immune-mediated inflammation of the renal interstitium — the signature kidney injury of checkpoint inhibitors.
Pseudo-AKIRarequalitative — no citable incidence
The great mimic — a rise in creatinine from blocked tubular secretion (OCT2/MATE), NOT true injury. The GFR is intact; confirm with cystatin C before stopping effective therapy.
Fanconi SyndromeRarequalitative — no citable incidence
Global failure of proximal tubule reabsorption — glucosuria, phosphaturia and acidosis, classically from ifosfamide.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

21%incidence

SeverityMild

ReversibilityReversible

Evidence8 citations

Nephron map

Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)

Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water

Interstitium

Acute Tubular Necrosis

Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.

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Kidney injury

Mechanism of kidney injury

Tubulointerstitial injury with direct tubular and glomerular epithelial cytotoxicity (mechanism incompletely defined).

Clinical presentation

Rising creatinine and electrolyte abnormalities (hypokalemia, hyponatremia, hypophosphatemia); usually mild.

Management

Dose adjust/hold, electrolyte repletion, supportive care.Lesion-level management framework

Risk factors

Vemurafenib (vs dabrafenib)
Volume depletion
Concurrent nephrotoxins

Prevention

Rehydrate and treat drug-induced pyrexia early (especially on dabrafenib + trametinib) — febrile dehydration is the dominant route to AKI in this class
Replete phosphate, potassium and magnesium for the vemurafenib Fanconi-type proximal tubular pattern

Anticancer mechanism· how it treats cancer

Vemurafenib and dabrafenib inhibit mutant BRAF (V600E); trametinib inhibits downstream MEK — shutting down MAPK signaling. BRAF-mutant melanoma and others.

Note · Switching vemurafenib → dabrafenib may reduce renal toxicity.

§04

Clinical depth

Renal dose adjustment

No CrCl-based dose adjustment is established for the BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) or MEK inhibitors (trametinib, cobimetinib, binimetinib) — all are hepatically metabolized small molecules with low renal elimination, so mild-to-moderate impairment is not expected to require change. Manage emergent AKI by holding the drug and treating the precipitant (pyrexia/volume loss) rather than by reducing dose for GFR; data in severe impairment/dialysis are limited (class-level guidance).

Dialyzability & ESKD dosing

Not appreciably dialyzable as a class — these agents are highly protein-bound, non-renally cleared small molecules, so hemodialysis is not expected to remove meaningful drug. No ESKD-specific dosing guidance exists; standard dosing with clinical monitoring is reasonable (limited data).

Differential diagnosis

Separate the benign vemurafenib creatinine bump (modest, stable, from inhibition of tubular creatinine secretion — eGFR underestimates true GFR; confirm with cystatin C or measured GFR) from true AKI. Distinguish febrile/GI prerenal AKI–ATN (dabrafenib/trametinib pyrexia, volume loss; responds to rehydration) and the reported vemurafenib proximal-tubular/Fanconi electrolyte pattern from MEK-inhibitor edema-related hemodynamic creatinine shifts and from concurrent nephrotoxins (contrast, NSAIDs).

Monitoring

Baseline and serial creatinine/eGFR — vemurafenib in particular causes a reversible creatinine rise (partly tubular-secretion blockade, partly true AKI), so trend it rather than react to a single value.
Basic metabolic panel for electrolytes — watch for hypophosphatemia/hypokalemia and a Fanconi-type proximal tubular pattern reported with vemurafenib; check magnesium given concurrent GI losses.
During any drug-induced pyrexia (especially dabrafenib/trametinib), check renal function and volume status promptly — febrile dehydration is the dominant route to prerenal AKI/ATN in this class.
Reassess creatinine after holding/resuming or down-titrating for febrile or GI toxicity; most creatinine elevations recover, supporting the reversible class profile.
If a MEK inhibitor causes peripheral edema/fluid retention, distinguish hemodynamic creatinine shifts from structural injury before attributing AKI to the drug.

Key trials & series

BRIM-3 — registrational phase 3 of single-agent vemurafenib vs dacarbazine in BRAF V600E melanoma; established the BRAF inhibitor against which the class's pyrexia/photosensitivity and creatinine-rise signal was first characterized.
coBRIM — vemurafenib plus the MEK inhibitor cobimetinib vs vemurafenib alone; the combination context in which renal/electrolyte and edema toxicities of dual blockade were reported.
COMBI-d / COMBI-v — phase 3 trials of dabrafenib plus trametinib (vs placebo and vs vemurafenib); defined the D+T combination whose hallmark drug-induced pyrexia is the principal driver of prerenal AKI in this class.

Clinical pearls

Drug-induced pyrexia is the signature toxicity of dabrafenib + trametinib and is the main mechanism of AKI in this class — the kidney injury is usually febrile prerenal/ATN, reversible with antipyretics, drug hold, and rehydration.
A Fanconi-like proximal tubulopathy (hypophosphatemia, hypokalemia, glycosuria) has been described with vemurafenib — check electrolytes, not just creatinine.
MEK inhibitors (trametinib, cobimetinib, binimetinib) have minimal intrinsic nephrotoxicity; their renal-relevant effects are peripheral edema/fluid retention and rare CK-elevation/rhabdomyolysis, so a creatinine change usually reflects hemodynamics rather than structural damage.
Overall the class signal is mild and reversible — most AKI is hemodynamic and recovers with supportive care and a drug hold; structural irreversible nephrotoxicity is not a defining feature.

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

Class-level context for the major non-renal toxicities of the BRAF/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. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

4 references · 2015–2022 · 2 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· 4

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 · ModerateAcute kidney injury in patients with severe rash on vemurafenib treatment for metastatic melanomas.Regnier-Rosencher E et al. · Br J Dermatol 2013 · PMID 23909652Case series of four melanoma patients developing acute kidney injury accompanying a severe cutaneous drug reaction on vemurafenib, reversible on drug interruption/dose reduction.CaseB · ModerateDabrafenib- and trametinib-associated glomerular toxicity: A case report.Jo E et al. · Medicine (Baltimore) 2022 · PMID 3502990180-year-old woman on dabrafenib/trametinib for melanoma with progressive renal failure (Cr 1.59 to 5.46 mg/dL); two biopsies showed glomerular endothelial damage then FSGS and tubulointerstitial fibrosis, progressing to dialysis. Distinct glomerular/endothelial (anti-VEGF-like) BRAF/MEK injury.CaseC · LimitedAcute renal failure under encorafenib, binimetinib and cetuximab for BRAF V600E-mutated colorectal cancer.Stammler R et al. · Eur J Cancer 2021 · PMID 33618199Describes acute kidney injury with tubular injury during encorafenib/binimetinib (BRAF/MEK inhibitor) therapy in colorectal cancer, with recovery after withdrawal.CaseC · LimitedFanconi syndrome induced by vemurafenib: a new renal adverse event.Denis D et al. · JAMA Dermatol 2015 · PMID 25494458Reports vemurafenib-induced proximal tubular dysfunction (Fanconi syndrome) in a melanoma patient, a tubular nephrotoxicity of a BRAF inhibitor.

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 BRAF / MEK Inhibitors 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

Cobimetinib

Cotellic · MEK inhibitor

Profile

Real-world AKI signal with BRAF partners.

ATNAIN

Mild#1 · 71% phenotype match

Encorafenib

Braftovi · BRAF inhibitor

Profile

Class tubular signal; usually mild.

ATNAIN

Mild#2 · 71% phenotype match

Vemurafenib

Zelboraf · BRAF inhibitor

Profile

Strongest renal offender of the BRAF/MEK class: proximal tubular injury/Fanconi and early AKI.

ATNFANCLYTE

Moderate#3 · 69% phenotype match

Dabrafenib

Tafinlar · BRAF inhibitor

Profile

Milder than vemurafenib; pyrexia-driven AKI, rare granulomatous AIN, hyponatremia.

AINPRELYTE

Mild#4 · 63% phenotype match

Azacitidine

Vidaza · Hypomethylating agent

Profile

Proximal (type 2) RTA / Fanconi-like tubulopathy; overt AKI uncommon.

FANCATNLYTE

Moderate#5 · 62% phenotype match

Imatinib

Gleevec · BCR-ABL TKI

Profile

Fluid retention; rare Fanconi and AKI.

LYTEFANCATN

Mild#6 · 58% phenotype match

Compare BRAF / MEK Inhibitors 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.

Who studies this

The leading contributors to BRAF / MEK Inhibitors’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 BRAF / MEK Inhibitors; 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 75 clinical records among all 100 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.