Cisplatin
Platinol · Platinum agent
Proximal tubular ATN + magnesium wasting; the archetype.
ATNLYTEPRE
SevereOpen →
BRAF/MEK inhibitor
BRAF / MEK Inhibitors
Zelboraf · Tafinlar · Mekinist · BRAF/MEK
Mild but real — vemurafenib carries the strongest tubular signal of the class.
MildMAPK-pathway targeted therapy · approved 2011
BRAF-mutant melanomaNSCLCThyroid
Signature kidney injury
Acute Tubular Necrosis
No denominator-based rate; pharmacovigilance shows vemurafenib > dabrafenib. Mild creatinine elevation common, serious AKI uncommon.
Source: Jhaveri et al., JAMA Oncol 2015
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)
Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water
Interstitium
Acute Tubular Necrosis
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
Mechanism of kidney injury
Tubulointerstitial injury with direct tubular and glomerular epithelial cytotoxicity (mechanism incompletely defined); vemurafenib carries a stronger AKI signal than dabrafenib.
Clinical presentation
Rising creatinine and electrolyte abnormalities (hypokalemia, hyponatremia, hypophosphatemia); usually mild.
Onset
Acute–subacute during therapy.
Reversibility
Reversible
Anticancer mechanism
Vemurafenib and dabrafenib inhibit mutant BRAF (V600E); trametinib inhibits downstream MEK — shutting down MAPK signaling. BRAF-mutant melanoma and others.
Management
Dose adjust/hold, electrolyte repletion, supportive care.
Risk factors
- Vemurafenib (vs dabrafenib)
- Volume depletion
- Concurrent nephrotoxins
Prevention
- Monitor creatinine and electrolytes
- Hydration
Note · Switching vemurafenib → dabrafenib may reduce renal toxicity.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Interstitium
Supporting tissue around the tubules
Injury signatures
Acute Tubular NecrosisAcute Interstitial NephritisElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of braf/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
3 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkNephrotoxicity of the BRAF Inhibitors Vemurafenib and Dabrafenib.Jhaveri KD et al. · JAMA Oncol 2015 · PMID 26182194Landmark pharmacovigilance analysis of BRAF-inhibitor AKI.PMIDBRAF inhibitors - do we need to worry about kidney injury?Wanchoo R et al. · Expert Opin Drug Saf 2016 · PMID 26954036Review of BRAF-inhibitor renal safety and monitoring.PMIDBRAF/MEK inhibitor-associated nephrotoxicity in a real-world setting and human kidney cells.Sanagawa A et al. · Anticancer Drugs 2021 · PMID 34232935Real-world signal plus in vitro tubular cytotoxicity across the class.