Creatinine was 84?mol/L at the end of September 2015. reduction in the size of the other nodules, nivolumab was reintroduced after renal function improvement. Low-dose corticosteroids were first maintained during nivolumab treatment and subsequently discontinued. Only one month after prednisolone discontinuation, creatinine levels TAS-116 increased. A second kidney biopsy confirmed relapse of acute interstitial nephritis. Conclusions To our knowledge, this is the first case of nivolumab-induced acute interstitial immune nephritis. This case highlights that anti-PD-1 immunotherapy may be continued when renal function is usually adequate, and this requires close conversation between dermatologists and nephrologists. This adverse effect should be made known to prescribers as nivolumab is usually associated with significant improvement of survival in metastatic melanoma and may be used in many different types of cancer. strong class=”kwd-title” Keywords: Pd-1, Melanoma, Acute kidney injury, Acute interstitial immune nephritis, Immunotherapy Background The anti-Programmed Death receptor 1 (PD-1) antibodies nivolumab and pembrolizumab are new therapies in metastatic melanoma [1, 2] and immunotherapy aimed at this target is expanding to other cancers. Immunotherapies are best known to be responsible for thrombotic microangiopathy. However, immune interstitial nephritis has been described in a patient treated by nivolumab and ipilimumab concomitantly [3], and three cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy [4, 5]. Case report A 76Cyear-old woman was diagnosed in October 2012 with an anal canal non-mutated BRAF melanoma (Mucosal Lentiginous Melanoma in vertical growth phase, Breslow thickness 20?mm, presence of ulceration, pT4bN0M0, stage IIC). Sentinel lymph node was negative and wide local excision of in situ melanoma was confirmed to have safe margin. She also had a history of high blood pressure that was controlled by olmesartan, a right invasive ductal carcinoma (breast cancer, Scarff, Bloom and Richardson score III, pT1cN0M0) treated by Gdnf surgery, radiotherapy and anastrozole in June 2013, asthma, and asymptomatic distal pulmonary embolism. Multiple metastatic pulmonary nodules were discovered in January 2015. Melanoma relapse was proven by histological examination of a lung nodule biopsy. From January 19, 2015 to March 23, 2015 she received 4 intravenous cycles of ipilimumab (3?mg/kg) for first-line treatment. She presented only grade 1 diarrhea; no additional immune adverse event was observed. Ipilimumab response was evaluated at 16?weeks and disease progression was found (according to RECIST criteria). Second-line treatment with nivolumab (3?mg/kg) was initiated on May 18, 2015 (8?weeks after ipilimumab discontinuation). She presented acute kidney injury after three cycles of nivolumab: creatinine was 69?mol/L before nivolumab initiation, 75?mol/L before the second cycle, 94?mol/L before the third cycle, and 142?mol/L before the fourth cycle. Immunotherapy was discontinued and a non-contrast computed tomography (CT) scan confirmed the absence of any obstacle in the urinary tract. She did not receive any other drug that could explain the increased creatinine level. Stage 2 acute kidney injury was estimated according to KDIGO criteria. Urinalysis found subnormal microscopic glomerular hematuria (18/mm3), and leukocyturia (34/mm3) mainly composed of neutrophils; protein excretion, infection, eosinophils, lymphocytes, and crystal deposits were not found. Moreover, serum protein electrophoresis was normal. The patient was not taking nephrotoxic drugs and was otherwise asymptomatic. Despite an adequate fluid intake over 3?days, renal failure persisted and therefore renal biopsy was performed. Morphological examination of the kidney (Fig. ?(Fig.1)1) found interstitial edema with dense and nodular inflammatory infiltrates with tubulitis and patchy tubular necrosis. The inflammatory cells were predominantly mononuclear, with focally numerous plasma cells and some eosinophils without any granular or giant cell. Neither glomerular nor vascular lesion was found. TAS-116 No deposit was observed by indirect immunofluorescence. Nivolumab-induced acute immune interstitial nephritis was diagnosed. Open in a separate window Fig. 1 Kidney pathology specimen, HES 1000 (hematoxylin, eosin, saffron). Interstitial infiltrate with plasma cells associated with patchy tubular necrosis This renal injury was then treated by oral prednisolone at a daily dose of 0.5?mg/kg (40?mg). Renal function rapidly improved although creatinine remained higher than before initiation of nivolumab TAS-116 (Fig. ?(Fig.2)2) and glomerular filtration rate was estimated to be 42?mL/min/1.73m2 (Chronic Kidney Disease – Epidemiology Collaboration method) at the end of August. The.
