Acute granulomatous interstitial nephritis in a patient with metastatic melanoma on targeted therapy with dabrafenib and trametinib<i>—</i>A case report

Krelle, Anna; Mathai, Vinod Kalapurackal; Kirkland, G; Nott, Louise M.; Jose, Matthew; Whale, Karen

doi:10.1002/cnr2.1520

Cited by 7 publications

(3 citation statements)

References 14 publications

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“…However, there are multiple cases of dabrafenib/trametinib combination therapy resulting in drug-induced sarcoid-like reactions with granulomatosis. Interestingly, these patients most commonly presented with skin lesions but rarely had evidence of solid organ involvement, such as the liver and kidney, with 1 patient presenting after 5 years of continuous therapy with interstitial nephritis 10,11 . It is not known which patients are at increased risk of developing dabrafenib/trametinib-induced systemic granulomatous reactions, what the optimal therapy is, and in which cases discontinuation of therapy is necessary 10 …”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, these patients most commonly presented with skin lesions but rarely had evidence of solid organ involvement, such as the liver and kidney, with 1 patient presenting after 5 years of continuous therapy with interstitial nephritis. [10,11] It is not known which patients are at increased risk of developing dabrafenib/trametinib-induced systemic granulomatous reactions, what the optimal therapy is, and in which cases discontinuation of therapy is necessary. [10] There is also a theoretical potential for synergistic hepatotoxicity when PKIs are used with other potentially hepatotoxic drugs.…”

Section: Discussionmentioning

confidence: 99%

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Granulomatous hepatitis: Is it bugs, drugs, or other untoward culprits?

Shah,

Dib,

Joseph

et al. 2024

Clinical Liver Disease

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Granulomatous hepatitis: Is it bugs, drugs, or other untoward culprits?

Shah,

Dib,

Joseph

et al. 2024

Clinical Liver Disease

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“…To date, 3 cases of tubulointerstitial nephritis [4,9,10] and 1 case of nephrotic syndrome [5] have been reported following combined treatment with dabrafenib and trametinib. An additional case of glomerulonephritis has been described, but this patient had been treated earlier with the immune checkpoint inhibitors ipilimumab and nivolumab [11] .…”

Section: Discussionmentioning

confidence: 99%

Dabrafenib- and trametinib-associated glomerular toxicity

Rhee

2022

Medicine

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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.

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Acute granulomatous interstitial nephritis in a patient with metastatic melanoma on targeted therapy with dabrafenib and trametinib—A case report

et al. 2021

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Background: Combination molecular targeted therapy with dabrafenib plus trametinib has been shown to improve progression-free survival and overall survival in patients with BRAF V600 mutated unresectable or metastatic melanoma. In general, these agents are well tolerated. Kidney related adverse events are uncommon with only three case reports of acute interstitial nephritis and one case of a serious acute kidney injury. We report another case of interstitial nephritis related to these drugs.

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Acute granulomatous interstitial nephritis in a patient with metastatic melanoma on targeted therapy with dabrafenib and trametinib—A case report

Cited by 7 publications

References 14 publications

Granulomatous hepatitis: Is it bugs, drugs, or other untoward culprits?

Granulomatous hepatitis: Is it bugs, drugs, or other untoward culprits?

Dabrafenib- and trametinib-associated glomerular toxicity

Acute granulomatous interstitial nephritis in a patient with metastatic melanoma on targeted therapy with dabrafenib and trametinib—A case report

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