A Case of Acute Interstitial Nephritis Associated with Belvarafenib, a Novel pan-RAF Kinase Inhibitor for Metastatic NRAS Mutant Melanoma
Bibliographic record
Abstract
Introduction: Belvarafenib is a potent oral type II pan-RAF kinase inhibitor that inhibits B-Raf V600E- and C-Raf-mediated signal transduction pathways and mutated Ras proteins, thereby demonstrating growth suppression of cancer with RAF or RAS mutation. This novel therapy has limited known adverse effects, with no reported kidney-related adverse events. Here, we present a case of interstitial nephritis associated with Belvarafenib treatment. Case Description: A 79-year-old woman was diagnosed with stage IV melanoma (wild-type BRAF) with NRAS mutation on the pan-RAF agent (Belvarafenib). Eight months into the treatment, she presented to the melanoma clinic with nausea, fatigue, and severe weakness. The patient was pale on physical examination, and her vital signs were normal. Laboratory investigations revealed a serum creatinine of 260 μmol/L (from baseline 90 μmol/L) and protein trace in urinalysis with no leukocyturia or hematuria. Urine microscopy showed granular casts consistent with acute tubular necrosis. The kidney function was not improved despite hydration and discontinuing Belvarafanib. A kidney core biopsy revealed acute interstitial nephritis drug-related and acute tubular injury. She was treated with prednisolone1 mg/kg with improved renal function. Discussion: Acute renal injury, particularly acute interstitial nephritis, is not a recognized side effect of Belvarafenib. This is the first reported case of a pan-RAF agent kidney adverse effects manifested by AIN and ATI. A literature review reported no renal adverse effects associated with pan-RAF agents. Belvarafenib is a novel agent; further research and time are required to determine its adverse effects incidence. However, clinicians must remain vigilant about the potential kidney adverse effects of this agent and consider a kidney biopsy to assess AIN in patients whose AKI does not respond promptly to discontinuing Belvarafenib and supportive care.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".