Bortezomib Eliminates Plasma Cells From a Renal Graft in Plasma Cell-Rich Acute Rejection.

Plasma cell-rich acute rejection (PCAR) and antibody-mediated rejection (ABMR), for which a standard treatment has not yet been established, are associated with poor graft survival after kidney transplantation. Here, we report a case series of 3 Japanese patients diagnosed with PCAR accompanied by ABMR. Steroid pulse therapy and rabbit antithymocyte globulin, plasma exchange, intravenous immunoglobulin, and rituximab therapies were sequentially performed in the first case. A graft biopsy after each treatment showed that plasma cell infiltration persisted. Five months after the initiation of rejection therapy, the patient was subjected to bortezomib therapy, which led to the partial elimination of plasma cells from the graft. However, the graft function gradually deteriorated, and hemodialysis treatment was warranted. In the other 2 cases, the patients received the same combination of therapy including bortezomib within a short period. Graft biopsies performed subsequently showed a marked decrease in the number of infiltrated plasma cells, and stabilization of renal graft function was achieved in both cases. Bortezomib, which targets plasma cells, is a potent drug that eliminates infiltrated plasma cells from the graft in PCAR. Thus, in addition to conventional therapy comprising plasma exchange, intravenous immunoglobulin, and rituximab against ABMR, bortezomib may be necessary to administer without any delay to control PCAR.

Drug-induced kidney disease: a study of the Japan Renal Biopsy Registry from 2007 to 2015.

INTRODUCTION: The Japan Renal Biopsy Registry (J-RBR) was started in 2007 by the Committee for the Standardization of Renal Pathological Diagnosis and the Committee for the Kidney Disease Registry of the Japanese Society of Nephrology. The purpose of this report is to clarify drug-induced kidney disease (DIKD) of renal biopsied cases in Japan. SUBJECTS AND METHODS: We analyzed the data of 26,535 cases that were registered in the J-RBR from 2007 to 2015. RESULTS: Based on clinical and pathological diagnoses, 328 cases (176 males and 152 females) of renal biopsy-proven DIKD were registered in the J-RBR from 2007 to 2015 (1.24 % of all cases). The frequency of DIKD increased with age. The number of cases peaked in the 6th-8th decade in all pathological categories, except for the number of chronic tubulointerstitial lesions (CTIL), which peaked in the 4th-5th decade. Overall, the frequency of DIKD was 3 times higher in the 7th decade than in the 2nd decade (1.86 vs. 0.62 %). The main clinical diagnoses were DIKD in 150 cases (45.7 %), nephrotic syndrome in 66 cases (20.1 %), chronic nephritic syndrome in 55 cases (16.8 %), and rapidly progressive glomerulonephritis in 30 cases (9.1 %). DIKD was registered as a secondary diagnosis in 136 cases (41.5 %). The pathological findings of these cases were glomerular lesions in 105 cases (32.0 %), acute tubulointerstitial lesions (ATIL) in 87 cases (26.5 %), CTIL in 72 cases (22.0 %), and sclerotic glomerular lesions and/or nephrosclerosis in 18 cases (5.5 %). ATIL and CTIL were mainly found in cases in which DIKD was diagnosed on the basis of the patient's clinical findings. In addition, nephrotic syndrome-related membranous nephropathy (MN) was the major cause of renal damage in 59.4 % of the cases involving glomerular injuries. According to the CGA risk classification, high-risk (red zone) cases accounted for 56.1 % of all cases of DIKD and 75.9, 64.9, and 33.3 % of the cases involving ATIL, CTIL, and glomerular injuries, respectively. The causative drugs were identified in 102 cases, including bucillamine in 38 cases of MN, gemcitabine in 3 cases of thrombotic microangiopathy, and other anticancer drugs in 14 cases (anti-vascular endothelial growth factor drugs in 3 cases and propyl thiouracil in 3 cases of anti-neutrophil cytoplasmic antibody-related nephritis). CONCLUSION: Our analysis of the J-RBR revealed that DIKD mainly affects elderly people in Japan. ATIL or CTIL were found in approximately half of the biopsied cases of DIKD, and one-third involved glomerular lesions, mainly MN or clinical nephrotic syndrome.