== Periodic acidSchiff staining and Periodic AcidMethenamine Silver stain demonstrated thickening of glomerular basement membranesawith a bubble-like appearance (b; red arrow) == Fig

== Periodic acidSchiff staining and Periodic AcidMethenamine Silver stain demonstrated thickening of glomerular basement membranesawith a bubble-like appearance (b; red arrow) == Fig.3. and immune-mediated glomerulonephropathy. Keywords:Anti-programmed cell death-1 antibody, Acute tubulointerstitial nephritis, Immune-mediated glomerulonephropathy == Introduction == Immune checkpoint inhibitors (ICIs) are attracting attention as novel cancer therapeutic agents against multiple cancer species, such as melanoma, non-small-cell lung carcinoma, and renal cell carcinoma [13]. These agents are monoclonal antibodies targeting anti-cytotoxic T-lymphocyte-associated protein-4 and anti-programmed death-1 (PD-1) signaling pathways. Nivolumab (anti-PD-1 antibody) is considered to enhance tumor-directed immune response by reactivation of cytotoxic T cell, leading to tumor cell lysis [4]. On the other hand, ICIs have been associated with numerous unique side effects, termed immune-related adverse events (irAEs). IrAEs occur IL27RA antibody in up to 60% of treated patients, usually mild to moderate in grade. The pathophysiology of irAEs is possibly mediated through non-specific immune activation against self-antigens [5]. The most Limonin commonly reported irAEs include skin rash, colitis, hepatitis, hypophysitis, interstitial pneumonia, and type 1 diabetes [5]. According to previous reports, renal irAEs are less frequent than other organ involvement [6]. Furthermore, most cases of renal irAEs present as acute tubulointerstitial nephritis; however, IgM deposition on glomerular capillary walls triggered by nivolumab has not been previously reported [7]. Herein, we present the case of a patient with metastatic clear cell renal cell carcinoma treated with nivolumab, who developed acute tubulointerstitial nephritis and immune-mediated glomerulonephropathy. == Case report == A 59-year-old Japanese man was referred and admitted to our department owing to progressive deterioration of renal function and new onset proteinuria after immunotherapy Limonin with nivolumab. With regard to the patients history, he was referred to our medical center with kidney tumor and nephrotic syndrome 4 years previously. Left nephrectomy was performed for treatment of renal cell carcinoma (cT2N2M0) diagnosed using positron emission tomographycomputed tomography. Histopathological analysis of the nephrectomy specimens confirmed clear cell renal cell carcinoma of the left kidney and minor glomerular abnormalities (Fig.1). Immunofluorescence study demonstrated absence of deposits of immunoglobulins and complements. Electron microscopy showed extensive foot process effacement without any immune complex deposits (Fig.1). Surgical resection of the tumor resulted in complete remission of proteinuria without corticosteroid therapy. After operation, the patient received several adjuvant therapies, including sunitinib, sorafenib, and pazopanib. However, 3 years after the initial diagnosis, the cancer progressed to stage IV (T0N2M1) with multiple metastases to the bone, adrenal grand, and spleen. He was then started on biweekly treatments with nivolumab (3 mg/kg, by intravenous drip infusion). Although nivolumab was effective, an acute increase in Limonin serum creatinine (Cre) levels (from 1.13 to 2.39 mg/dL) was observed approximately 4 months after initiation of nivolumab. His medications were rosuvastatin for dyslipidemia, esomeprazole for gastroesophageal reflux disease, and pregabalin for chronic Limonin pain. == Fig. 1. == Histological findings on nephrectomy specimens. Light microscopy revealed minor glomerular abnormality (a,b). Electron microscopy showed extensive foot process effacement without any immune complex deposits (c,d) On admission, his height was 172 cm, body weight was 60.9 kg, blood pressure was 123/84 mmHg, and pulse rate was 93/min. Physical examination revealed no abnormal clinical signs, such as ophthalmologic findings suggesting uveitis. Urinalysis showed proteinuria (1.5 g/day), mild hematuria (1019/HPF), and a few granular casts.N-acetyl–d-glucosaminidase activity and -2 microglobulin were elevated at 36.3 U/L and 7754 g/L, respectively. The results of laboratory blood tests were as follows: white blood cell count 9900/L, with 71.6% neutrophils, 2.4% eosinophils, hemoglobin 12.1 g/dL, platelet count 26.2 104/L, serum albumin 3.7 g/dL, serum Cre 3.09 mg/dL, blood urea nitrogen 35.8 mg/dL, C-reactive protein 1.9 mg/dL, IgG4 33.5 mg/dL (0.9%), and angiotensin-converting enzyme 9.6 U/L. Furthermore, tests were negative for anti-nuclear, anti-neutrophil cytoplasmic, anti-Sjogren syndrome (SS)-A, and anti-SS-B antibodies (Table1). == Table 1. == Laboratory data at renal biopsy Renal Limonin biopsy was immediately performed to clarify the cause of worsening renal function. It contained total 17 glomeruli, of which 4 demonstrated global sclerosis. Light microscopy revealed.