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Dabrafenib- and trametinib-associated glomerular toxicity: A case report
RATIONALE: Combined treatment with dabrafenib, a B-RAF inhibitor, and trametinib, a mitogen-activated protein kinase inhibitor, is an effective option for patients with metastatic melanoma. A few cases of acute kidney injury associated with tubulointerstitial nephritis and 1 case of nephrotic syndro...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8735797/ https://www.ncbi.nlm.nih.gov/pubmed/35029901 http://dx.doi.org/10.1097/MD.0000000000028485 |
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author | Jo, Eunmi Rhee, Harin |
author_facet | Jo, Eunmi Rhee, Harin |
author_sort | Jo, Eunmi |
collection | PubMed |
description | RATIONALE: Combined treatment with dabrafenib, a B-RAF inhibitor, and trametinib, a mitogen-activated protein kinase inhibitor, is an effective option for patients with metastatic melanoma. A few cases of acute kidney injury associated with tubulointerstitial nephritis and 1 case of nephrotic syndrome have been reported in patients on this drug combination; however, progressive renal injury has not been reported. In this case study, we report a patient with metastatic melanoma who developed glomerular capillary endothelial toxicity and progressive glomerular sclerosis during combination therapy. PATIENT CONCERN: Our patient was an 80-year-old woman with a history of type 2 diabetes and chronic kidney disease. DIAGNOSIS AND INTERVENTION: She was diagnosed with metastatic melanoma and commenced combination therapy with dabrafenib and trametinib. OUTCOMES: Her renal function progressively deteriorated; by month 20 after treatment commencement, her serum creatinine level had increased from 1.59 to 3.74 mg/dL. The first kidney biopsy revealed marked glomerular and endothelial cell damage. Her medication was stopped, but no improvement was evident. At 5 months after the first biopsy, her serum creatinine level had increased to 5.46 mg/dL; a second kidney biopsy revealed focal segmental glomerular sclerosis and marked tubulointerstitial fibrosis. She was started on hemodialysis. LESSONS: We describe a patient with a metastatic melanoma who developed progressive kidney failure during treatment with dabrafenib and trametinib. The most prominent microscopy findings were glomerular endothelial damage in the initial kidney biopsy and accelerated glomerular sclerosis and tubulointerstitial fibrosis in the follow-up biopsy. We hypothesize that a decreased renal reserve and impairment of kidney repair capacity caused by inhibition of B-RAF, a downstream mediator of vascular endothelial growth factor, may explain the progressive kidney injury. |
format | Online Article Text |
id | pubmed-8735797 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-87357972022-01-11 Dabrafenib- and trametinib-associated glomerular toxicity: A case report Jo, Eunmi Rhee, Harin Medicine (Baltimore) 5200 RATIONALE: Combined treatment with dabrafenib, a B-RAF inhibitor, and trametinib, a mitogen-activated protein kinase inhibitor, is an effective option for patients with metastatic melanoma. A few cases of acute kidney injury associated with tubulointerstitial nephritis and 1 case of nephrotic syndrome have been reported in patients on this drug combination; however, progressive renal injury has not been reported. In this case study, we report a patient with metastatic melanoma who developed glomerular capillary endothelial toxicity and progressive glomerular sclerosis during combination therapy. PATIENT CONCERN: Our patient was an 80-year-old woman with a history of type 2 diabetes and chronic kidney disease. DIAGNOSIS AND INTERVENTION: She was diagnosed with metastatic melanoma and commenced combination therapy with dabrafenib and trametinib. OUTCOMES: Her renal function progressively deteriorated; by month 20 after treatment commencement, her serum creatinine level had increased from 1.59 to 3.74 mg/dL. The first kidney biopsy revealed marked glomerular and endothelial cell damage. Her medication was stopped, but no improvement was evident. At 5 months after the first biopsy, her serum creatinine level had increased to 5.46 mg/dL; a second kidney biopsy revealed focal segmental glomerular sclerosis and marked tubulointerstitial fibrosis. She was started on hemodialysis. LESSONS: We describe a patient with a metastatic melanoma who developed progressive kidney failure during treatment with dabrafenib and trametinib. The most prominent microscopy findings were glomerular endothelial damage in the initial kidney biopsy and accelerated glomerular sclerosis and tubulointerstitial fibrosis in the follow-up biopsy. We hypothesize that a decreased renal reserve and impairment of kidney repair capacity caused by inhibition of B-RAF, a downstream mediator of vascular endothelial growth factor, may explain the progressive kidney injury. Lippincott Williams & Wilkins 2022-01-07 /pmc/articles/PMC8735797/ /pubmed/35029901 http://dx.doi.org/10.1097/MD.0000000000028485 Text en Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | 5200 Jo, Eunmi Rhee, Harin Dabrafenib- and trametinib-associated glomerular toxicity: A case report |
title | Dabrafenib- and trametinib-associated glomerular toxicity: A case report |
title_full | Dabrafenib- and trametinib-associated glomerular toxicity: A case report |
title_fullStr | Dabrafenib- and trametinib-associated glomerular toxicity: A case report |
title_full_unstemmed | Dabrafenib- and trametinib-associated glomerular toxicity: A case report |
title_short | Dabrafenib- and trametinib-associated glomerular toxicity: A case report |
title_sort | dabrafenib- and trametinib-associated glomerular toxicity: a case report |
topic | 5200 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8735797/ https://www.ncbi.nlm.nih.gov/pubmed/35029901 http://dx.doi.org/10.1097/MD.0000000000028485 |
work_keys_str_mv | AT joeunmi dabrafenibandtrametinibassociatedglomerulartoxicityacasereport AT rheeharin dabrafenibandtrametinibassociatedglomerulartoxicityacasereport |