Hitoshi Nakashima

In immunoglobulin G4-related kidney disease (IgG4-RKD), focal or diffuse renal cortical atrophy is often observed in the clinical course after glucocorticoid therapy. This study aimed to clarify the factors related to renal atrophy after glucocorticoid therapy in IgG4-RKD. We retrospectively evaluated clinical features including laboratory data and computed tomography (CT) findings before and after glucocorticoid therapy in 23 patients diagnosed with IgG4-RKD, all of whom were followed up for more than 24 months. Seventeen patients were men, and six were women (average age 62.0 years). Average follow-up period was 54.9 months. The average estimated glomerular filtration rate (eGFR) at diagnosis was 81.7 mL/min/1.73 m2. All patients had had multiple low-density lesions on contrast-enhanced CT before glucocorticoid therapy, and showed disappearance or reduction of these lesions after it. Pre-treatment eGFR and serum IgE level in 11 patients in whom renal cortical atrophy developed 24 months after the start of glucocorticoid therapy were significantly different from those in 12 patients in whom no obvious atrophy was found at that time (68.9 ± 30.1 vs 93.5 ± 14.1 mL/min/1.73 m2, P = 0.036, and 587 ± 254 vs 284 ± 263 IU/mL, P = 0.008, respectively). Pre-treatment eGFR and serum IgE level were also significant risk factors for renal atrophy development 24 months after the start of therapy with an odds ratio of 0.520 (per 10 mL/min/1.73 m2, 95% confidence interval (CI) 0.273–0.993, P = 0.048) and 1.090 (per 10 IU/mL, 95% CI: 1.013–1.174, P = 0.022), respectively, in age-adjusted, sex-adjusted, serum IgG4 level-adjusted logistic regression analysis. Receiver operating characteristic curve analysis showed that eGFR of less than 71.0 mL/min/1.73 m2 and serum IgE of more than 436.5 IU/mL were the most appropriate cutoffs and yielded sensitivity of 63.6% and specificity of 100%, and sensitivity of 90.9% and specificity of 75.0%, respectively, in predicting renal atrophy development. This study suggests that pre-treatment renal insufficiency and serum IgE elevation predict renal atrophy development after glucocorticoid therapy in IgG4-RKD.

Background More than 2 years have passed since the proposal of the diagnostic criteria for IgG4-related kidney disease (IgG4-RKD). The aim of this study was to estimate the number of histological diagnosis for IgG4-RKD throughout Japan and to clarify the regional distribution of the development of this disease. Methods A questionnaire was supplied to 140 research facilities registered in the Japan Renal Biopsy Registry (J-RBR). The items of the questionnaire were the total number of renal biopsies performed and the number of cases diagnosed as IgG4-RKD in 2012 and 2013 at each facility. Age, sex, and diagnosis category were also included for the IgG4-RKD cases. The geographic distribution of the disease development was evaluated using clinical case reports presented at the Eastern/Western regional meeting of the Japanese Society of Nephrology during the 15 years following 2001. Results Forty-seven facilities completed the questionnaire, resulting in a collection rate of 34 %. The total numbers of renal biopsies in 2012 and 2013 were 3387 and 3591, respectively. Forty-seven of these cases (24 in 2012 and 23 in 2013) were diagnosed as IgG4-RKD. The frequency of development of IgG4-RKD per one million over 40-year-old individuals during these 15 years varied between 0.9 and 3.1, depending on Japanese geographic region of Japan. Conclusion The results of the present survey indicate that the number of diagnosis for IgG4-RKD is approximately 130 cases per year throughout Japan, and no regional differences in disease frequency appear to exist.

A twenty-year-old man complaining of chest pain was diagnosed as nephrotic syndrome complicated with pleural effusion and ascites. Despite treatment with antibiotics, his fever and high inflammatory reaction persisted. After hospitalization, his urine volume decreased and renal function had deteriorated. As he was suffering from dyspnea, hemodialysis was performed together with chest drainage. His pleural effusion was exudative, and IVIG treatment was added to the antibiotic treatment. He was diagnosed as suspected developed minimal change nephrotic syndrome (MCNS) and administered prednisolone intravenously. His renal function ameliorated as a result of this treatment, enabling him to withdraw from hemodialysis. Inflammatory reaction gradually decreased and his general condition improved. The result of a renal biopsy examination carried out after the hemodialysis treatment confirmed MCNS, which suggested that MCNS had induced acute kidney injury (AKI) atypically in this case. Generally AKI is not induced by MCNS in youth, but it may occur under severe inflammatory conditions. Physicians should be aware that MCNS in young patients may lead to the development of AKI requiring hemodialysis treatment.

30歳女性. 10年以上前に健診にて尿異常を指摘されたが放置していた. 2014年2月から眼瞼周囲の掻痒感があり, 5月に近医眼科を受診した. 点眼薬, 軟膏で加療したが改善せず, 内科疾患を疑われ5月下旬, 近医内科を受診した. その際に急性腎障害を疑われ当院に紹介され入院した. 精査の結果, 原疾患不明であるが末期腎不全の状態であり, 腹膜透析導入となった. 本症例は以前より月経不順があり, 約3年前の月経を最後に無月経が継続していた. 血液検査, 経直腸超音波にて, 多囊胞性卵巣症候群 (PCOS : polycystic ovary syndrome) と診断された. Kaufmann療法を行い, 消褪出血を認めた. 妊娠適齢期の腎不全患者の無月経は, 腎不全によるものだけではなく, 治療可能な産婦人科的疾患も念頭に考えなければならない.

Incretin therapy is feasible in patients with type 2 diabetes mellitus undergoing hemodialysis (HD). However, few studies have examined the safety and efficacy of this therapeutic approach in patients with diabetes and renal impairment. Here, we examined glycemic control and the anti-oxidative-stress effects of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin in patients with type 2 diabetes undergoing HD. Thirty-five patients with type 2 diabetes undergoing HD (including 13 insulin-treated patients) were switched from ongoing therapy to linagliptin (5 mg, once daily). Levels of fasting blood glucose, C-peptide immunoreactivity (CPR), glycated albumin, B-type natriuretic peptide, oxidized low-density lipoprotein (oxLDL), high-sensitivity C-reactive protein, 8-hydroxy-2′-deoxyguanosine (8OHdG), body mass index, blood pressure, and other biologic characteristics (liver function, renal function, lipid profile) were determined before and 3 months after linagliptin treatment. Patients were classified into insulin-treated and non-insulin groups. With the exception of levels of total bilirubin, aspartate aminotransferase, and CPR, none of the patients exhibited changes in glucose metabolism after switching to linagliptin treatment. However, oxLDL levels were decreased significantly by linagliptin therapy in the non-insulin-treated group despite the absence of changes in glycemic control. Linagliptin can decrease serum levels of oxLDL in patients with type 2 diabetes undergoing HD independent of its glucose-lowering effect.

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus and manifests with considerable phenotypic and histological heterogeneity. In particular, diffuse proliferative lupus nephritis (DPLN) and membranous lupus nephritis (MLN) represent morphologic forms that are polar opposites. DPLN is associated with autoimmune responses dominated by Th1 immune response associated with high levels of interferon (IFN)-γ. In contrast, a Th2 cytokine response is associated with the pathogenesis of MLN. MRL/lpr mice develop human LN-like immune complex-associated nephritis and provide a suitable histological model for human DPLN. Infection with Schistosoma mansoni skewed a Th2-type immune response induction and IL-10 in MRL/lpr mice, drastically changing the pathophysiology of glomerulonephritis from DPLN to MLN accompanied by increased IgG1 and IgE in the sera. T cells in 32-week-old MRL/lpr mice infected with S. mansoni expressed significantly more IL-4 and IL-10 than T cells of uninfected mice; T cells with IFN-γ were comparable between infected and uninfected MR/lpr mice. Thus, the helminthic infection modified the cytokine microenvironment and altered the pathological phenotype of autoimmune nephritis.

This study aimed to evaluate the remission in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ), based on prospectively registered data in clinical practice.

Background: Although incretin therapy is clinically available in patients with type 2 diabetes undergoing hemodialysis, no study has yet examined whether incretin therapy is capable of maintaining glycemic control in this group of patients when switched from insulin therapy. In this study, we examined the efficacy of incretin therapy in patients with insulin-treated type 2 diabetes undergoing hemodialysis. Methods: Ten type 2 diabetic patients undergoing hemodialysis received daily 0.3 mg liraglutide, 50 mg vildagliptin, and 6.25 mg alogliptin switched from insulin therapy on both the day of hemodialysis and the non-hemodialysis day. Blood glucose level was monitored by continuous glucose monitoring. After blood glucose control by insulin, patients were treated with three types of incretin therapy in a randomized crossover manner, with continuous glucose monitoring performed for each treatment. Results: During treatment with incretin therapies, severe hyperglycemia and ketosis were not observed in any patients. Maximum blood glucose and mean blood glucose on the day of hemodialysis were significantly lower after treatment with liraglutide compared with treatment with alogliptin (p < 0.05), but not with vildagliptin. The standard deviation value, a marker of glucose fluctuation, on the non-hemodialysis day was significantly lower after treatment with liraglutide compared with treatment with insulin and alogliptin (p < 0.05), but not with vildagliptin. Furthermore, the duration of hyperglycemia was significantly shorter after treatment with liraglutide on both the hemodialysis and non-hemodialysis days compared with treatment with alogliptin (p < 0.05), but not with vildagliptin. Conclusions: The data presented here suggest that patients with type 2 diabetes undergoing hemodialysis and insulin therapy could be treated with incretin therapy in some cases.