What kind of kidney injury does Encorafenib 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.

Is kidney injury from Encorafenib reversible?

Reversible. Typical onset: Weeks into therapy when it occurs..

How should kidney function be monitored during Encorafenib therapy?

Creatine phosphokinase periodically (with binimetinib) and with any myalgia; ECG/QTc and LVEF per label given the combined cardiac signal; Serum creatinine and electrolytes at baseline and periodically.

How can kidney injury from Encorafenib be prevented?

Review and minimize concomitant AIN-associated drugs (PPIs, NSAIDs) before and during therapy Maintain euvolemia, especially during GI toxicity or intercurrent illness

Who is at higher risk of kidney injury from Encorafenib?

Concurrent nephrotoxins or other AIN-associated drugs (PPIs, NSAIDs); Volume depletion; Pre-existing CKD.

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Printable monograph

BRAF inhibitor

Encorafenib

Braftovi · Enco

BRAF inhibitor · approved 2018 · 9 citations · FAERS AKI reporting ROR 3.17 (95% CI 2.78–3.62, 223 AKI reports)

Aging evidence· through 2022

Fairly sourced5/9 · 5 signals

Met: 9 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 5y)
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 BRAF inhibitor whose kidney signal is a mild, usually class-shared tubular/interstitial effect.

MildBRAF inhibitor

BRAF V600-mutant melanomaBRAF V600E-mutant metastatic colorectal cancer

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

Renal injury with BRAF/MEK therapy is uncommon and largely case-level (tubular injury and acute interstitial nephritis reported); usually mild and reversible with drug interruption. In COLUMBUS, grade 3-4 creatine-phosphokinase elevation (7%) and hypertension (6%) were the renally relevant events with encorafenib plus binimetinib.Source: Sanagawa et al., Anticancer Drugs 2021

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Weeks into therapy when it occurs.

Distilled from: “Weeks into therapy when it occurs.”

§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.
Acute Interstitial NephritisSecondaryqualitative — no citable incidence
Immune-mediated inflammation of the renal interstitium — the signature kidney injury of checkpoint inhibitors.

§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

BRAF/MEK pathway inhibition has been associated in case reports, real-world pharmacovigilance, and human kidney-cell models with proximal tubular injury and acute interstitial nephritis; the precise mechanism is not fully defined and the signal is typically mild relative to vemurafenib. Indirect injury can also arise from MEK-inhibitor-related CK elevation/rhabdomyolysis when binimetinib is co-administered.

Clinical presentation

Modest creatinine rise, occasionally with electrolyte changes; biopsy-proven acute interstitial nephritis (sometimes with eosinophilia, sterile pyuria, or sub-nephrotic proteinuria) has been described with BRAF/MEK regimens. Often reversible after holding therapy, with or without corticosteroids.

Management

Hold drug for significant AKI; supportive care and volume repletion; corticosteroids if biopsy-proven (or strongly suspected) interstitial nephritis; rechallenge cautiously — case data describe successfully switching to the alternative BRAF/MEK regimen after AIN.Lesion-level management framework

Risk factors

Concurrent nephrotoxins or other AIN-associated drugs (PPIs, NSAIDs)
Volume depletion
Pre-existing CKD

Prevention

Review and minimize concomitant AIN-associated drugs (PPIs, NSAIDs) before and during therapy
Maintain euvolemia, especially during GI toxicity or intercurrent illness

Anticancer mechanism· how it treats cancer

Selective inhibitor of mutant BRAF V600E/K kinase with a long target-residence time, blocking constitutive MAPK pathway signaling. Used (with binimetinib) in BRAF V600-mutant melanoma and (with cetuximab) in BRAF V600E-mutant colorectal cancer.

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Clinical depth

Renal dose adjustment

No dedicated renal dose adjustment established; no change recommended for mild-moderate impairment, and severe impairment/dialysis are not studied (use with caution). Dose modifications are driven mainly by CK, hepatic, and cardiac (QT) toxicity.

Dialyzability & ESKD dosing

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

Differential diagnosis

BRAF/MEK-associated AIN vs prerenal azotemia (volume status, FENa), vs ATN from co-nephrotoxins or rhabdomyolysis (check CK, urine myoglobin), vs immune-checkpoint-inhibitor AIN if prior/concurrent ICI. Eosinophiluria and sterile pyuria favor AIN but are neither sensitive nor specific.

Monitoring

Creatine phosphokinase periodically (with binimetinib) and with any myalgia
ECG/QTc and LVEF per label given the combined cardiac signal
Serum creatinine and electrolytes at baseline and periodically

Key trials & series

COLUMBUS (encorafenib + binimetinib vs vemurafenib in BRAF-mutant melanoma)
BEACON CRC (encorafenib + cetuximab in BRAF V600E colorectal cancer)
Sanagawa 2021 real-world BRAF/MEK nephrotoxicity analysis

Clinical pearls

Encorafenib's renal signal is largely extrapolated from the BRAF/MEK class — drug-specific data are limited, so keep the differential broad.
With a binimetinib partner, a rising creatinine plus myalgia should prompt a CK to exclude rhabdomyolysis.
Biopsy-proven AIN can sometimes be managed by switching to the alternative BRAF/MEK combination rather than abandoning targeted therapy.

Where it strikes· nephron segments & injury signatures

Nephron segments

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Interstitium

Supporting tissue around the tubules

Injury signatures

Acute Tubular Necrosis Acute Interstitial Nephritis

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

Class-level context for the major non-renal toxicities of the BRAF 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

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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 · 3 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 28640105Case report of biopsy-proven renal injury (glomerulonephritis with granulomatous vasculitis, with BRAF-inhibitor renal events including interstitial nephritis/acute tubular necrosis) on encorafenib plus binimetinib, with encorafenib identified as the likely culprit.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 (acute kidney injury) developing in a patient on encorafenib/binimetinib/cetuximab for BRAF V600E colorectal cancer, with renal recovery.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 (tubular injury) arising in a melanoma patient treated with encorafenib plus binimetinib.

FDA label — boxed warning & renal dosing· renal impairment

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

Renal impairment — from the label

No BRAFTOVI dosage adjustment is recommended in patients with mild to moderate renal impairment (CLcr 30 to <90 mL/min) [see Clinical Pharmacology (12.3) ] . A recommended dosage has not been established in patients with severe renal impairment (CLcr <30 mL/min).

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 9,844 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

Acute Interstitial Nephritiscorroborated · ROR 2.51
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 2.5195% CI 1.65–3.81· 22 reports

Electrolyte Disturbance

ROR 1.8395% CI 1.57–2.14· 163 reports

SIADH / Hyponatremia

ROR 1.6495% CI 1.28–2.11· 62 reports

FAERS outcomes & reporting trend· 16.5% of reports w/ death · 27.8% w/ hospitalization

16.5%

Reported with a death outcome

1,627 of 9,844 reports

27.8%

Reported with hospitalization

2,733 of 9,844 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 10 systems · 9,844 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 3.1795% CI 2.78–3.62· 223 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 Injury223

Gastrointestinal

Nausea842Diarrhoea634Vomiting478Constipation213Abdominal Pain190

General / constitutional

Fatigue770Pyrexia599Malaise295Asthenia249Pain226

Skin

Rash470Pruritus171

Musculoskeletal

Arthralgia323Myalgia161

Eye

Vision Blurred223Visual Impairment196

Metabolic & electrolyte

Decreased Appetite306

Nervous system

Headache198

Blood & lymphatic

Anaemia189

Respiratory

Dyspnoea159

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 Encorafenib 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 · 100% phenotype match

Procarbazine

Matulane · Hydrazine alkylating agent

Profile

Classic cytotoxic with recognized renal/urological complications; AKI usually multifactorial; hypersensitivity AIN possible.

ATNAIN

Moderate#2 · 82% phenotype match

BRAF / MEK inhibitors (vemurafenib · dabrafenib · trametinib)

BRAF/MEK inhibitor

Profile

Tubulointerstitial AKI; vemurafenib strongest.

ATNAINLYTE

Mild#3 · 71% phenotype match

Dabrafenib

Tafinlar · BRAF inhibitor

Profile

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

AINPRELYTE

Mild#4 · 61% phenotype match

Vemurafenib

Zelboraf · BRAF inhibitor

Profile

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

ATNFANCLYTE

Moderate#5 · 54% phenotype match

Bicalutamide

Casodex · Nonsteroidal antiandrogen

Profile

Hepatically cleared, kidney-neutral, no renal dose adjustment; only rare idiosyncratic interstitial nephritis.

AIN

Mild#6 · 53% phenotype match

Compare Encorafenib 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 Encorafenib’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 Encorafenib; 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 6 clinical records among all 9 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.