Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
MEK inhibitor
Binimetinib
Mektovi · Bini
A MEK inhibitor whose renal signal is a modest creatinine rise — with rare rhabdomyolysis reports.
MildMEK inhibitor · approved 2018
BRAF V600-mutant melanoma (with encorafenib)
Signature kidney injury
Prerenal / Hemodynamic AKI
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)
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.
Onset
Weeks into therapy.
Reversibility
Reversible
Anticancer mechanism
Selective, reversible MEK1/2 inhibitor blocking MAPK signaling; given with encorafenib in BRAF V600-mutant melanoma.
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.
Risk factors
- Strenuous activity / statin co-use (CK)
- Volume depletion
- Pre-existing CKD
Prevention
- Monitor CK and creatinine at baseline and periodically
- Maintain hydration
- Investigate myalgia promptly
Note · Renal risk is mostly indirect (rare rhabdomyolysis); intrinsic nephrotoxicity is low.
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
- Serum creatinine and electrolytes periodically
- LVEF and ophthalmologic assessment per label
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
Vasculature / Endothelium
Glomerular & peritubular capillaries
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Prerenal / Hemodynamic AKIAcute Tubular Necrosis
Beyond the kidney
Class-level context for the major non-renal toxicities of mek inhibitors.
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
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkBRAF/MEK inhibitor-associated nephrotoxicity in a real-world setting and human kidney cells.Sanagawa A et al. · Anticancer Drugs 2021 · PMID 34232935Real-world and in vitro characterization of BRAF/MEK-class renal injury.PMIDEncorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial.Dummer R et al. · Lancet Oncol 2018 · PMID 29573941Pivotal trial quantifying grade 3-4 CK elevation (~7%) and hypertension with encorafenib + binimetinib.PMIDOverall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial.Dummer R et al. · Lancet Oncol 2018 · PMID 30219628Confirms the durable CK-elevation safety signal at the overall-survival analysis.PMIDTruth or dare: switching BRAF/MEK inhibitors after acute interstitial nephritis in a patient with metastatic melanoma - A case report and review of the literature.De Ryck L et al. · Acta Clin Belg 2022 · PMID 35996969Case-based review of renal injury and rechallenge with encorafenib/binimetinib-type regimens.PMIDTargeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition: A Case Report and Review of the Literature.Mach T et al. · Can J Kidney Health Dis 2022 · PMID 35756332Helps separate a transporter-mediated creatinine artifact from true pigment-nephropathy AKI in kinase-inhibitor patients.PMIDCurrent Trends in Anti-Cancer Molecular Targeted Therapies: Renal Complications and Their Histological Features.Tonooka A et al. · J Nippon Med Sch 2021 · PMID 34840210Onconephrology review of targeted-therapy renal complications.
Related agents
Other agents sharing the same signature kidney injury.