Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
MEK inhibitor
Selumetinib
Koselugo · Selu
A pediatric MEK inhibitor for neurofibromatosis — kidney effects are modest and rarely limiting.
MildMEK inhibitor · approved 2020
Neurofibromatosis type 1 with inoperable plexiform neurofibromas (pediatric)
Signature kidney injury
Prerenal / Hemodynamic AKI
Long-term pediatric trial data (SPRINT, up to ~5 years) show a manageable safety profile with no new safety signals; significant nephrotoxicity is not prominent, with creatinine changes generally modest. CK elevation is a recognized MEK-class laboratory effect.
Source: Gross et al., Neuro Oncol 2023
Mechanism of kidney injury
No characteristic intrinsic nephrotoxic mechanism; as a MEK inhibitor it can raise CK and (rarely) cause rhabdomyolysis, a potential indirect cause of pigment tubular injury. Modest creatinine changes are within class expectations and may partly reflect tubular-secretion inhibition. GI losses (diarrhea, vomiting) can produce prerenal azotemia in children.
Clinical presentation
Generally mild; possible modest creatinine change and asymptomatic CK elevation. Diarrhea, rash, paronychia, and (rarely) reduced ejection fraction dominate the pediatric toxicity profile; dehydration from GI losses is the most common pathway to AKI.
Onset
Variable; adverse events can appear after prolonged dosing.
Reversibility
Reversible
Anticancer mechanism
Selective MEK1/2 inhibitor that dampens MAPK signaling driven by NF1 loss; approved for children with neurofibromatosis type 1 and symptomatic inoperable plexiform neurofibromas.
Management
Supportive care; hold for marked CK rise/rhabdomyolysis with IV fluids; replace volume and correct electrolytes during GI losses; dose-modify per protocol for grade 3 events.
Risk factors
- Dehydration (pediatric, GI losses)
- Strenuous activity (CK)
- Pre-existing renal disease
Prevention
- Maintain hydration, especially during GI toxicity
- Monitor CK and creatinine
- Manage diarrhea/vomiting promptly
Note · Renal-specific data are limited; safety is drawn from pediatric NF1 trials where nephrotoxicity was not prominent.
Clinical depth
Renal dose adjustment
Weight/BSA-based pediatric dosing; no specific renal adjustment established (renal-impairment data are limited in this young population). Hepatic impairment, not renal, carries label dose guidance.
Dialyzability & ESKD dosing
Highly protein-bound oral small molecule; dialyzability not characterized and not clinically relevant in this indication. No ESKD dosing data.
Differential diagnosis
In a child with rising creatinine, separate prerenal azotemia from GI volume losses (responds to fluids), MEK-related CK elevation/rhabdomyolysis (check CK), and a transporter-mediated creatinine artifact.
Monitoring
- Creatine phosphokinase at baseline and periodically, and with myalgia
- Serum creatinine and electrolytes, especially during diarrhea/vomiting
- LVEF (echocardiogram) and ophthalmologic assessment per label
Key trials & series
- SPRINT phase 1/2 (pediatric NF1 plexiform neurofibromas)
- Gross 2023 long-term SPRINT safety update
Clinical pearls
- In NF1, the commonest route to AKI is dehydration from diarrhea/vomiting — rehydrate early rather than reflexively stopping the drug.
- Check CK with myalgia; asymptomatic CK elevation is a class effect.
- Renal-specific data are thin; safety is largely extrapolated from pediatric NF1 trials where nephrotoxicity was not prominent.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Prerenal / Hemodynamic AKIElectrolyte Wasting
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.
LandmarkLong-term safety and efficacy of selumetinib in children with neurofibromatosis type 1 on a phase 1/2 trial for inoperable plexiform neurofibromas.Gross AM et al. · Neuro Oncol 2023 · PMID 37115514Up to ~5-year pediatric safety data (SPRINT) with no new safety signals.PMIDBRAF/MEK inhibitor-associated nephrotoxicity in a real-world setting and human kidney cells.Sanagawa A et al. · Anticancer Drugs 2021 · PMID 34232935Class-level characterization of MEK-inhibitor renal effects.PMIDMEK inhibitors in RASopathies.Bergqvist C et al. · Curr Opin Oncol 2021 · PMID 33395032Review of selumetinib in NF1 (SPRINT) and the MEK-inhibitor class, framing tolerability in pediatric RASopathies.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 35996969Class case-based review of MEK/BRAF-inhibitor interstitial nephritis informing the renal differential for selumetinib.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 35756332Context for interpreting modest creatinine changes on kinase inhibitors as transporter-mediated rather than true injury.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 providing class context for MEK-inhibitor renal effects.
Related agents
Other agents sharing the same signature kidney injury.