AKI DURING TREATMENT OF MALIGNANCY— NEW CULPRITS

Metastatic melanoma treatment includes immune-checkpoint inhibitors (ICIs) or targeted therapy.1 This case investigates the etiology of acute interstitial nephritis (AIN) in a patient transitioned from ICIs to BRAF-MEK inhibitors (BRAFi/MEKi).

A 73-year-old man with melanoma and lung metastases presented to the ER for weakness and fevers for 1 month. Six weeks prior, he received nivolumab plus ipilimumab. Two weeks later, testing revealed a BRAF V600E mutation, he was transitioned to BRAFi/MEKi— dabrafenib and trametinib. Within a week, he reported fevers and diarrhea leading to this hospitalization. On admission, labs included creatinine 6.3 mg/dL (baseline 1.3), BUN 114, WBC 11.2 K/uL, platelets 45, d-dimer 3.94, fibrinogen 187, INR 3.3, uric acid 10.4 mg/dL, calcium 6.3, phosphorous 7.3, albumin 2.4 g/dL. Few schistocytes were reported on the peripheral blood smear. Urinalysis: Glucose neg, protein neg, mod blood, no leukocyte esterase, RBC 6, WBC 2, specific gravity 1.017, hyaline cast 1, UACR:129, UPCR:1.27. CT chest showed an opacity in the lower lobe, suggesting pneumonia. Antibiotics were initiated for presumed sepsis and the patient was admitted to the ICU. The differential included disseminated intravascular coagulation and tumor lysis syndrome. His kidney function failed to improve; he started CRRT and methylprednisolone. All cultures showed no growth. Two days later, his renal function recovered, and his UA displayed granular 27 and hyaline casts 3. A renal biopsy confirmed AIN from likely medications with melanuria-induced tubular inflammation (Figure 2). He was discharged home in stable condition with a steroid taper. BRAFi/MEKi were not restarted, and melanoma has remained inactive more than 2 years.

ICI and BRAFi/MEKi kidney injuries are uncommon, with ICIs ranging from 1.4-2.0% for monotherapy and 4.9-5.1% with combination therapy.2,3 One review noted 40% of ICI kidney injuries have other adverse events such as thyroiditis, colitis, hepatitis, median onset 14 weeks.4 BRAFi/MEKi renal injuries seem under-reported. Dabrafenib insert states AIN occurs < 10% and does not define a frequency for trametinib.5,6 However, a retrospective study found 21% experienced AKI within 12 months of dabrafenib and 24% had concurrent febrile episodes, attributed to dabrafenib and trametinib.7 Three published case series suggest one form of injury appears immediately after BRAFi/MEKi initiation in 1-2 weeks, likely allergic interstitial nephritis and a second subacute AKI within 1-2 months of initiation, which is an acute tubular toxicity.8 Granular and hyaline casts as well as WBC/RBC can be found in urine in both early and late phases. Our patient had a melanin pigment in the tubular cells, postulated to cause AKI in one case previously.9 The rapid AKI with tubular and interstitial injury just one week after BRAFi/MEKi suggests a combination of BRAFi/MEKi injury and melanuria induced AKI. 

Although ICI AIN is more known, BRAFi/MEKi may have been the culprit. The febrile syndrome was likely BRAFi/MEKi related pyrexia. We also report a rare immune reaction mediated by melanin-induced inflammation.9 Identifying the condition can guide future therapeutic options and a renal biopsy should be considered in severe toxicity. 

This abstract was submitted to the Society of Hospital Medicine 2025.

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