Dabrafenib- and trametinib-associated glomerular toxicity: A case report

Area of Science:

• Oncology
• Nephrology
• Pharmacology

Background:

• Combined dabrafenib (B-RAF inhibitor) and trametinib (MAPK inhibitor) is effective for metastatic melanoma.
• Previous reports noted rare acute kidney injury and nephrotic syndrome with this combination.
• Progressive renal injury has not been previously documented.

Observation:

• An 80-year-old woman with metastatic melanoma and pre-existing chronic kidney disease received combination therapy.
• She experienced progressive renal function deterioration over 20 months.
• Kidney biopsies showed glomerular endothelial damage and later, focal segmental glomerulosclerosis and tubulointerstitial fibrosis.

Findings:

• The patient developed progressive kidney failure requiring hemodialysis.
• Microscopic findings included glomerular capillary endothelial toxicity and progressive glomerular sclerosis.
• Renal function did not improve after medication cessation.

Implications:

• This case suggests a potential for progressive kidney injury with dabrafenib and trametinib combination therapy.
• Inhibition of B-RAF may impair kidney repair capacity, especially in patients with reduced renal reserve.
• Further investigation into the renal safety profile of this melanoma treatment is warranted.