Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
MEK inhibitor
Mirdametinib
Gomekli · MIRD
A MEK inhibitor for NF1 plexiform neurofibromas whose renal footprint is edema and modest creatinine shifts.
MildMEK inhibitor · approved 2025
NF1-associated plexiform neurofibromas (adult and pediatric)
Signature kidney injury
Prerenal / Hemodynamic AKI
No established intrinsic nephrotoxicity. Across MEK-inhibitor experience (including the NF106 mirdametinib trial) the characteristic toxicities are rash, edema, diarrhea and CK elevation; renal events are not a defining signal and any creatinine change is qualitative rather than a quantified AKI rate.
Source: Weiss et al., J Clin Oncol 2021
Mechanism of kidney injury
No characterized direct nephron injury. MEK inhibitors commonly cause peripheral edema and fluid retention and can produce hemodynamic shifts; a mild creatinine rise, if seen, is most consistent with prerenal/edema-related changes or diarrhea-driven GI volume loss rather than tubular damage. Class-associated rhabdomyolysis from marked CK elevation is a rare theoretical route to myoglobinuric AKI.
Clinical presentation
Peripheral/periorbital edema and weight gain; if present, a modest reversible creatinine increase with bland sediment; electrolytes generally track GI losses if diarrhea is prominent. Marked CK rise warrants checking for muscle injury.
Onset
Not well defined; edema and any creatinine changes evolve during ongoing therapy.
Reversibility
Reversible
Anticancer mechanism
Oral allosteric MEK1/2 inhibitor that blocks downstream MAPK/ERK signaling, shrinking neurofibromas in the constitutively active RAS/MAPK setting of neurofibromatosis type 1 (NF1, with loss of the RAS-GAP neurofibromin). Approved for adults and children with NF1-associated symptomatic, inoperable plexiform neurofibromas.
Management
Supportive: manage edema and diarrhea, ensure euvolemia, and interrupt/reduce dose per protocol for significant toxicity. Intrinsic renal injury has not been characterized; evaluate alternative causes before attributing AKI to the drug.
Risk factors
- Significant treatment-related diarrhea or edema
- Baseline cardiac/renal impairment
- Concurrent nephrotoxins or diuretics
Prevention
- Monitor weight, edema, creatinine and electrolytes on therapy
- Manage diarrhea and maintain hydration
- Standard MEK-inhibitor cardiac (LVEF), ocular and CK monitoring per label
Note · 2025 approval with minimal renal-specific data; the cited NF106 trial used the same agent (PD-0325901) in NF1 PN. Prerenal/edema framing is conservative MEK-class reasoning, not a quantified renal signal.
Clinical depth
Renal dose adjustment
No established renal dose adjustment; mirdametinib is hepatically metabolized with low renal elimination, so reduced GFR is not expected to require modification. Dosing is BSA-based in children. No data in severe impairment or dialysis.
Dialyzability & ESKD dosing
Not characterized; a small, protein-bound, non-renally cleared molecule is unlikely to be appreciably dialyzed. No ESKD dosing guidance.
Differential diagnosis
Distinguish edema/prerenal creatinine change (volume redistribution, responds to diuresis/euvolemia) from rare rhabdomyolysis-associated AKI (very high CK, pigmented sediment); structural MEK-inhibitor nephrotoxicity is not described.
Monitoring
- Serum creatinine and electrolytes periodically
- Weight and edema assessment each visit
- LVEF (echo) and ophthalmologic exam per MEK-inhibitor label
- CK if muscle symptoms
Key trials & series
- NF106 (Weiss, JCO 2021) — mirdametinib NF1 plexiform-neurofibroma trial
- ReNeu — registrational adult/pediatric NF1-PN study supporting 2025 approval
Clinical pearls
- Edema is the signature MEK-inhibitor effect — a small creatinine bump usually reflects fluid shifts, not tubular injury.
- Track CK: marked elevation is the one route to true (myoglobinuric) AKI in this class.
- Renal framing for this 2025 agent is conservative MEK-class reasoning, not a quantified signal.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
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
4 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkNF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas.Weiss BD et al. · J Clin Oncol 2021 · PMID 33507822Mirdametinib NF1 trial; toxicity profile (rash, edema, GI) without a defining renal signal underpins the qualitative assessment.PMIDTreatment decisions and the use of MEK inhibitors for children with neurofibromatosis type 1-related plexiform neurofibromas.Armstrong AE et al. · BMC Cancer 2023 · PMID 37328781Context on MEK-inhibitor use and tolerability (edema, GI, cardiac/ocular) in NF1 plexiform neurofibromas, framing class toxicity expectations.PMIDNew drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int 2015 · PMID 25671763Onconephrology review of targeted-agent renal/electrolyte effects supporting the low direct-tubular-risk, edema/prerenal framing for signaling-pathway inhibitors.PMIDOnconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens 2023 · PMID 38095483Onconephrology review of kinase/signaling-pathway-inhibitor renal effects and mitigation strategies.
Related agents
Other agents sharing the same signature kidney injury.