小出 滋久

INTRODUCTION: Degenerative aortic valve stenosis (AS) is a chronic progressive disease that resembles atherosclerosis development. Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is reportedly associated with accelerated atherosclerosis. This study aimed to examine the development of AS in patients with myeloperoxidase-AAV (MPO-AAV) with renal involvement at more than 1 year after the onset of vasculitis. METHODS: We performed a retrospective review of clinical records of MPO-AAV patients with renal involvement without AS at the onset of vasculitis who were treated in three hospitals and three dialysis clinics. RESULTS: The study included 97 MPO-AAV patients with renal involvement and 230 control patients with chronic kidney disease (CKD). Among them, 64 patients had AS. The prevalence rates of AS were 28.9% and 15.7% in MPO-AAV and control patients, respectively (p = 0.006). The multivariable logistic regression analysis showed that MPO-AAV, dialysis dependence, and hypertension were independently associated factors for AS. In MPO-AAV patients, systolic blood pressure was positively significantly associated with AS, whereas glucocorticoid dose of induction therapy was negatively significantly associated. The use of cyclophosphamide tended to be negatively associated with AS. The survival rate was significantly lower for patients with AS than for those without AS. CONCLUSIONS: The AS prevalence rate was significantly higher in MPO-AAV patients at more than 1 year after the onset of vasculitis than in control CKD patients. Therefore, regular monitoring of echocardiography during MPO-AAV treatment is suggested.

INTRODUCTION: There are few studies on the association between serum uric acid (UA) level and mortality in incident dialysis patients. We aimed to clarify whether the serum UA level at dialysis initiation is associated with mortality during maintenance dialysis. METHODS: We enrolled 1486 incident dialysis patients who participated in a previous multicenter prospective cohort study in Japan. We classified the patients into the following five groups according to their serum UA levels at dialysis initiation: G1 with a serum UA level <6 mg/dL; G2, 6.0-8.0 mg/dL; G3, 8.0-10.0 mg/dL; G4, 10.0-12.0 mg/dL; and G5, ≥12.0 mg/dL. We created three models (Model 1: adjusted for age and sex, Model 2: adjusted for Model 1 + 12 variables, and Model 3: stepwise regression adjusted for Model 2 + 13 variables) and performed a multivariate Cox proportional hazard regression analysis to examine the association between the serum UA level and outcomes, including infection-related mortality. RESULTS: Hazard ratios (HRs) were calculated relative to the G2, because the all-cause mortality rate was the lowest in G2. For Models 1 and 2, the all-cause mortality rate was significantly higher in G5 than in G2 (HR: 1.63, 95% confidence interval [CI]: 1.14-2.33 and HR: 1.78, 95% CI: 1.19-2.68, respectively). For Models 1, 2, and 3, the infection-related mortality rate was significantly higher in G5 than in G2 (HR: 2.75, 95% CI: 1.37-5.54, HR: 3.09, 95% CI: 1.45-6.59, HR: 3.37, and 95% CI: 1.24-9.15, respectively). CONCLUSIONS: Extreme hyperuricemia (serum UA level ≥12.0 mg/dL) at dialysis initiation is a risk factor for infection-related deaths.

INTRODUCTION: Albeit uncommon, hydrothorax is an important complication of peritoneal dialysis (PD). Due to paucity of evidence for optimal treatment, this study aimed to evaluate the effectiveness and safety of computed tomographic (CT) peritoneography and surgical intervention involving video-assisted thoracic surgery (VATS) for hydrothorax in a retrospective cohort of patients who underwent PD in Japan. METHODS: Of the 982 patients who underwent PD from six centers in Japan between 2007 and 2019, 25 (2.5%) with diagnosed hydrothorax were enrolled in this study. PD withdrawal rates were compared between patients who underwent VATS for diaphragm repair (surgical group) and those who did not (non-surgical group) using the Kaplan-Meier method and log-rank test. RESULTS: The surgical and non-surgical groups comprised a total of 11 (44%) and 14 (56%) patients, respectively. Following hydrothorax diagnosis by thoracentesis and detection of penetrated sites on the diaphragm using CT peritoneography, VATS was performed at a median time of 31 days (interquartile range [IQR], 20-96 days). During follow-up (median, 26 months; IQR, 10-51 months), 9 (64.3%) and 2 (18.2%) patients in the non-surgical and surgical groups, respectively, withdrew from PD (P = 0.021). There were no surgery-related complications or hydrothorax relapse in the surgical group. CONCLUSIONS: This study demonstrated the effectiveness and safety of CT peritoneography and VATS for hydrothorax. This approach may be useful in hydrothorax cases to avoid early drop out of PD and continue PD in the long term. Further studies are warranted to confirm these results.

Background: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD) events, and a number of reports have shown a relationship between CKD and CVD in pre-dialysis or maintenance dialysis patients. However, few studies have reported serial observations during dialysis initiation and maintenance. Therefore, we examined whether the incidence of heart disease events differed between CKD patients with and without a history of coronary heart disease (CHD) at dialysis initiation. Methods: The subjects were patients in the 17 centers participating in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) from October 2011 to September 2013. We excluded nine patients whose outcomes were unknown, as determined by a survey conducted at the end of March 2015. Thus, we enrolled 1,515 subjects into the study. We classified patients into 2 groups according to the history of CHD (i.e., a CHD group and a non-CHD group). Propensity scores (PS) represented the probability of being assigned to a group with or without a history of CHD. Onset of heart disease events and associated mortality and all-cause mortality were compared in PSmatched patients by using the log-rank test for Kaplan-Meier curves. Factors contributing to heart disease events were examined using stepwise multivariate Cox proportional hazards analysis. Results: There were 254 patients in each group after PS-matching. During observation, heart disease events occurred in 85 patients (33.5%) in the CHD group and 48 (18.9%) patients in the non-CHD group. The incidence was significantly higher in the CHD group (p &lt; 0.0001). The CHD group was associated with higher incidence of heart disease events (vs. the non-CHD group, hazard ratio = 1.750, 95% confidence interval = 1.160-2.639). In addition, comorbidities such as diabetes mellitus, low body mass index, and low serum high-density lipoprotein cholesterol were associated with higher incidence of events. Conclusion: History of CHD at dialysis initiation was associated with a higher incidence of heart disease events and mortality and all-cause mortality.

<p>Background: Cell-free and concentrated ascites reinfusion therapy (CART) was approved by the National Insurance Scheme in 1981 in Japan and has since been used as a treatment modality for refractory ascites. Two filtration methods may be used for CART: the internal and external pressure filtration methods. However, the precise characteristics of each method are unknown.</p><p>Methods: Ascitic fluid will be obtained by puncture from patients with refractory cancerous ascites. The quantity of fluid obtained from each patient will be divided in half, and each half will be processed using either the internal or external pressure filtration method. The primary endpoint will be the time required for the transmembrane pressure to reach 500 mmHg. The secondary endpoints will be serial changes in the weight of the ascitic and filtered fluid, serial changes in the pressure at the inlet and outlet of the filter, measurement of the components of the ascitic and filtered fluid, and observation of the filter by visual inspection and light and electron microscopy.</p><p>Conclusion: This trial may clarify the characteristics of the two filtration methods.</p><p>Trial registration: UMIN000025382.</p>

Objectives. This study investigated the clinical course of myeloperoxidase-antineutrophil cytoplasm autoantibody (MPO-ANCA)-associated vasculitis after starting dialysis.Methods. A retrospective review was conducted of the clinical charts of dialysis-dependent patients with MPO-ANCA-associated vasculitis who attended one of 8 associated clinics over the past 21 years.Results. Eighty-nine patients were included in the study; 88 had microscopic polyangiitis (MPA) and 1 had granulomatosis with polyangiitis. Of the 88 patients with MPA, 18 had renal-limited vasculitis. Twenty-one relapses occurred among 13 patients (frequency, 0.05 relapses/person-year; 95% confidence interval, 0.03-0.08). Mean time from start of dialysis to relapse was 65 59 months. Cox multivariate analysis showed that pulmonary involvement was a predictor of relapse (hazard ratio [HR], 21.4) and mortality (HR, 4.60), and that patient age (HR, 1.10) and cyclophosphamide use (HR, 0.20) were significant predictors of mortality. Postdialysis 1- and 5-year survival rates were 83.0% and 65.6%, respectively; infection was the most frequent cause of death.Conclusion. Pulmonary involvement was a predictor of relapse and mortality. Although relapse can occur long after the start of dialysis, incidence was low among dialysis-dependent patients. Prolonged maintenance immunosuppressive therapy might be limited to patients with pulmonary involvement in dialysis-dependent ANCA-associated vasculitis.

Background. Our aim was to assess plasma neutrophil gelatinase-associated lipocalin (NGAL) as a predictor of cardiovascular (CV) events in patients with chronic kidney disease (CKD) and no history of CV events. Methods. This was a prospective observational cohort study of 252 patients with predialysis CKD. CV events were defined as CV death, acute coronary syndrome, and hospitalization for worsening heart failure, stroke, and aortic dissection. Results. During a median follow-up period of 63 months, 36 CV events occurred. On Cox stepwise multivariate analysis, plasma NGAL and B-type natriuretic peptide (BNP) were significant predictors of CV events. Kaplan-Meier incidence rates of CV event-free survival at 5 years were 96.6%, 92.9%, 85.9%, and 61.3%, respectively, among quartiles of plasma NGAL (P &lt; 0.0001). The C-index for the receiver-operating characteristic curves for CV events was greater when plasma NGAL was added to an established risk model (0.801, 95% CI 0.717-0.885), compared to the model without plasma NGAL (0.746, 95% CI 0.653-0.840, P = 0.021). Conclusion. Elevated plasma NGAL could predict future CV events in CKD patients with no history of CV events and add incremental value to the established risk model.

Renal parenchymal lesions in patients with IgG4-related kidney disease (IgG4-RKD) are characterized by tubulointerstitial nephritis with storiform fibrosis and infiltration by high numbers of IgG4-positive plasma cells. The aim of this study was to evaluate the clinical and pathological effects of corticosteroid therapy in patients with IgG4-RKD. Of six patients who were diagnosed with IgG4-RKD, four patients underwent re-biopsy at approximately 30-50 days after corticosteroid therapy was initiated. Based on the classification of Yamaguchi et al., the degree of tubulointerstitial fibrosis was classified before and after therapy. In addition, tubulointerstitial expression patterns of alpha-smooth muscle actin (alpha-SMA), collagen I, III, and IV protein, and connective tissue growth factor (CTGF) mRNA were examined. Histopathological findings before treatment showed alpha-SMA-positive myofibroblasts in the lesion, and CTGF mRNA-positive cells were found in the cellular infiltrate. Although corticosteroid therapy improved serum creatinine clinically, the stage of fibrosis advanced pathologically as evidenced by increased staining for collagen I and III. However, the number of IgG4-positive plasma cells decreased, and CTGF mRNA expression reduced. In other words, fibrosis had advanced from the time of extensive cell infiltration in patients with IgG4-RKD and inflammation was relieved by corticosteroid. A reduced number of positive CTGF mRNA expression cells in repeat biopsies indicated that the fibrosis process was terminated by corticosteroid therapy. We propose that corticosteroid therapy could terminate the pathway of active fibrosis, thereby inhibiting progression to renal dysfunction.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular (CV) events. Recently, elevated neutrophil gelatinase-associated lipocalin (NGAL) levels have been reported in patients with heart failure, coronary heart disease, or stroke. Our aim was to assess urinary NGAL as a predictor of CV events in patients with CKD. This was a prospective observational cohort study of 404 patients with predialysis CKD. CV events were defined as CV death, acute coronary syndrome, hospitalization for worsening heart failure, stroke and dissection of aorta. During a mean follow-up period of 33 months, 77 CV events (19.1 %) occurred. After adjustment for gender, age, diabetes, previous cardiovascular disease, urinary albumin/creatinine ratio (UACR), estimated glomerular filtration rate, hemoglobin, and high-sensitivity C-reactive protein, patients with the other quartiles of urinary NGAL had significantly higher risk of CV events compared with patients with the lowest quartile (hazard ratio (HR) 2.81, 95 % confidence interval (CI) 1.01-7.81, P = 0.047 for Q2, HR 3.31, 95 % CI 1.22-9.00, P = 0.019 for Q3, and HR 3.27, 95 % CI 1.15-9.29, P = 0.026 for Q4). Regarding the combination of urinary NGAL with UACR, we also stratified patients into four groups according to whether the level of each marker was above or below the median (61.8 mu g per gram creatinine (gCr) for NGAL and 351.1 mg/gCr for UACR). Four-year CV event-free survival rates were 89.2, 79.6, 71.8, and 51.5 % in order for the four respective groups (P &lt; 0.0001). Elevated urinary NGAL was able to predict future CV events in CKD patients, and had incremental predictive value with elevated UACR.

We evaluated the efficacy of granulocytaperesis and leukocytapheresis for the treatment of rapidly progressive glomerulonephritis (RPGN) and lung hemorrhage caused by microscopic polyangiitis. Three patients with RPGN were treated by granulocytapheresis (GCAP) and five patients with RPGN were treated by leukocytapheresis (LCAP). The prednisolone dose was 0.4 ± 0.2 g/kg/day (mean ± SD range 0.2-0.8 g/kg/day). Pre-treatment serum creatinine was 3.2 ± 1.4 mg/dL (1.4-5.1 mg/dL). The patients were followed for a mean period of 15 ± 6 months (6-23 months). Renal function improved in five of the eight RPGN patients. Three lung hemorrhage episodes in two different patients were treated with GCAP and one lung hemorrhage episode was treated with LCAP combined with various doses of corticosteroids. All four lung hemorrhage episodes were ameliorated. We concluded that combined therapy of GCAP or LCAP and corticosteroids is effective for the treatment of RPGN and lung hemorrhage due to microscopic polyangiitis.

Background. Maxacalcitol (22-oxacalcitriol OCT) is a novel vitamin D analogue. In previous clinical studies, OCT was administered three times a week to hemodialysis patients with refractory secondary hyperparathyroidism (2HPT), in whom it acted by inhibiting parathyroid hormone secretion, as well as causing mildly elevated serum calcium. However, intravenous injection of OCT, which requires frequent visits to the outpatient clinic, degrades the quality of life of patients with continuous ambulatory peritoneal dialysis (CAPD) who otherwise visit the clinic only once or twice per month. In the present study, we investigated whether transperitoneal absorption of OCT inhibited intact parathyroid hormone (i-PTH) in CAPD patients when the OCT was added to the peritoneal dialysis fluid. Methods. Peritoneal dialysis fluid containing 20 μg of OCT was injected into the peritoneal cavity of five CAPD patients. The serum and peritoneal fluid levels of OCT, i-PTH, calcium, and phosphate were measured before and after treatment. Results. The mean concentration of OCT in peritoneal dialysis fluid rapidly decreased, from 25268.0 pg/ml at 0 h to 1694.0 pg/ml at 2 h and 44.9 pg/ml at 4 h. In contrast, the mean serum OCT level increased from the pretreatment level, which was below the detection limit of the assay, to 656.0 g/ml at 0.5 h and a peak of 759.0 pg/ml at 1 h, and thereafter gradually decreased, to 713.8 pg/ml at 2 h and 555.8 pg/ml at 4 h. Mean i-PTH significantly decreased, to 83.9% of the baseline level, at 1 h (P &lt 0.05) and thereafter stayed at around 90%. No consistent trends in calcium and phosphate levels were observed in the five patients. Conclusions. By injecting OCT into the peritoneal cavity, i-PTH levels could be significantly decreased. These findings indicate the therapeutic efficacy of intraperitoneal administration of OCT for CAPD patients.