What kind of kidney injury does Cobimetinib 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 Cobimetinib reversible?

Reversible. Typical onset: Weeks into therapy..

How should kidney function be monitored during Cobimetinib therapy?

Creatine phosphokinase at baseline and periodically (rhabdomyolysis risk); LVEF and ophthalmologic assessment per label; Serum creatinine and electrolytes periodically.

How can kidney injury from Cobimetinib be prevented?

Maintain euvolemia and avoid concurrent nephrotoxins

Who is at higher risk of kidney injury from Cobimetinib?

Volume depletion; Concurrent nephrotoxins; Pre-existing CKD.

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Printable monograph

MEK inhibitor

Cobimetinib

Cotellic · Cobi

MEK inhibitor · approved 2015 · 7 citations · FAERS AKI reporting ROR 4.47 (95% CI 3.78–5.30, 139 AKI reports)

Aging evidence· through 2022

Fairly sourced5/9 · 5 signals

Met: 7 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 8y)
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 partnered with vemurafenib — it cut BRAF-inhibitor AKI in practice.

MildMEK inhibitor

BRAF V600-mutant melanoma (with vemurafenib)

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

AKI with BRAF/MEK therapy is uncommon and mostly mild; a pharmacovigilance analysis found adding a MEK inhibitor to vemurafenib was associated with a ~60% reduction in acute kidney injury versus vemurafenib alone.Source: Teuma et al., Cancer Chemother Pharmacol 2017

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

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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

MAPK-pathway inhibition can be associated with tubular injury or acute interstitial nephritis in case-level reports. Mechanistically the MEK component appears to mitigate the proximal-tubular injury attributed to the BRAF inhibitor vemurafenib (which itself can cause a Fanconi-like proximal tubulopathy and AIN), so the combination is renally protective relative to BRAF monotherapy.

Clinical presentation

Mild reversible creatinine elevation; occasional electrolyte disturbance. Severe AKI is unusual at standard combination dosing. CK elevation, photosensitivity, and serous retinopathy are other class/combination effects.

Management

Hold for significant AKI; supportive care and volume repletion; corticosteroids if interstitial nephritis is suspected/proven; resume per tolerance once renal function recovers.Lesion-level management framework

Risk factors

Volume depletion
Concurrent nephrotoxins
Pre-existing CKD

Prevention

Maintain euvolemia and avoid concurrent nephrotoxins

Anticancer mechanism· how it treats cancer

Selective, reversible MEK1/2 inhibitor that blocks MAPK signaling downstream of BRAF. Used with vemurafenib in BRAF V600-mutant melanoma.

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Clinical depth

Renal dose adjustment

No renal dose adjustment recommended for mild-moderate impairment; severe impairment and dialysis are not studied. Dose modification is driven mainly by CK elevation, retinopathy, LVEF, and photosensitivity.

Dialyzability & ESKD dosing

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

Differential diagnosis

When AKI does occur, distinguish vemurafenib-driven proximal tubulopathy/AIN (often the dominant contributor) from prerenal causes and from MEK-related rhabdomyolysis (check CK). Remember the combination tends to lower, not raise, AKI risk versus BRAF monotherapy.

Monitoring

Creatine phosphokinase at baseline and periodically (rhabdomyolysis risk)
LVEF and ophthalmologic assessment per label
Serum creatinine and electrolytes periodically

Key trials & series

coBRIM (cobimetinib + vemurafenib vs vemurafenib in BRAF-mutant melanoma)
Teuma 2017 pharmacovigilance analysis (MEK addition reduces BRAF-inhibitor AKI)

Clinical pearls

Counter-intuitively, adding the MEK inhibitor reduced BRAF-inhibitor AKI by ~60% in real-world data — the kidney signal here is favorable.
If AKI appears, vemurafenib (not cobimetinib) is the more likely culprit; consider a Fanconi-pattern proximal tubulopathy.
Check CK with any myalgia given MEK-inhibitor rhabdomyolysis risk.

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 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

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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 · 2014–2022 · 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· 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 · LimitedDRESS syndrome due to vemurafenib treatment: switching BRAF inhibitor to solve a big problem.Ros J et al. · BMJ Case Rep 2018 · PMID 30275021Case report of a melanoma patient on first-line vemurafenib plus cobimetinib who developed acute kidney injury (renal impairment, MeSH Acute Kidney Injury) as part of DRESS syndrome.

FDA label — boxed warning & renal dosing· renal impairment

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

Renal impairment — from the label

No dedicated pharmacokinetic trial in patients with renal impairment has been conducted. Dose adjustment is not recommended for mild to moderate renal impairment (CLcr 30 to 89 mL/min) based on the results of the population pharmacokinetic analysis. A recommended dose has not been established for patients with severe renal impairment [see Clinical Pharmacology (12.3) ].

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 4,389 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· 5 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 Tubular Necrosiscorroborated · ROR 2.92
Acute Interstitial Nephritiscorroborated · ROR 2.56

SIADH / Hyponatremia

ROR 3.4795% CI 2.68–4.50· 58 reports

Electrolyte Disturbance

ROR 3.3595% CI 2.81–3.98· 131 reports

Acute Tubular Necrosis

ROR 2.9295% CI 1.31–6.50· 6 reports

Acute Interstitial Nephritis

ROR 2.5695% CI 1.37–4.75· 10 reports

Glomerular Injury / Proteinuria

ROR 1.9795% CI 1.12–3.48· 12 reports

FAERS outcomes & reporting trend· 13.2% of reports w/ death · 45.6% w/ hospitalization

13.2%

Reported with a death outcome

579 of 4,389 reports

45.6%

Reported with hospitalization

2,000 of 4,389 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 10 systems · 4,389 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 4.4795% CI 3.78–5.30· 139 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 Injury139

Gastrointestinal

Diarrhoea441Nausea229Vomiting185

Skin

Rash398Photosensitivity Reaction132Rash Maculo-Papular124Skin Toxicity94Pruritus86

General / constitutional

Pyrexia366Fatigue217Asthenia133

Musculoskeletal

Arthralgia114Myalgia71

Immune / infection

Pneumonia94Sepsis79

Metabolic & electrolyte

Decreased Appetite89Dehydration74

Blood & lymphatic

Anaemia121

Respiratory

Dyspnoea102

Nervous system

Headache73

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 Cobimetinib 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

Encorafenib

Braftovi · BRAF inhibitor

Profile

Class tubular signal; usually mild.

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 Cobimetinib 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.