A chronic intermittent haemodialysis pig model for functional evaluation of dialysis membranes.

Performance evaluation of new dialysis membranes is primarily performed in vitro, which can lead to differences in clinical results. Currently, data on dialysis membrane performance and safety are available only for haemodialysis patients. Herein, we aimed to establish an in vivo animal model of dialysis that could be extrapolated to humans. We created a bilateral nephrectomy pig model of renal failure, which placed a double-lumen catheter with the hub exposed dorsally. Haemodialysis was performed in the same manner as in humans, during which clinically relevant physiologic data were evaluated. Next, to evaluate the utility of this model, the biocompatibility of two kinds of membranes coated with or without vitamin E used in haemodiafiltration therapy were compared. Haemodialysis treatment was successfully performed in nephrectomized pigs under the same dialysis conditions (4 h per session, every other day, for 2 weeks). In accordance with human clinical data, regular dialysis alleviated renal failure in pigs. The vitamin E-coated membrane showed a significant reduction rate of advanced oxidation protein products during dialysis than non-coated membrane. In conclusion, this model mimics the pathophysiology and dialysis condition of patients undergoing haemodialysis. This dialysis treatment model of renal failure will be useful for evaluating the performance and safety of dialysis membranes.

Cigarette smoking and progression of kidney dysfunction: a longitudinal cohort study.

INTRODUCTION: Cigarette smoking is one of the most important life-modifiable risk factors for CVD events. The effect on CKD progression caused by smoking remained uncertain, while the effect on CVD had been established. METHOD: The study population included participants from the specific health check and specific health guidance, an annual health check-up for all inhabitants of Japan who were aged between 40 and 74 years. 149,260 subjects (male, 37.1%; female, 62.9%) were included in this analysis. RESULTS: The relationship between smoking status along with new-onset proteinuria and eGFR deterioration more than 15 mL/min/1.73 m2 was examined. Median observation periods were 1427 days [738, 1813] in males and 1437 days [729, 1816] in females. In male participants, the strongest factor upon kidney dysfunction was new-onset proteinuria (1.41 [1.31 1.51], P < 0.001). The second strongest factor on kidney deterioration was smoking (1.24 [1.16 1.31], P < 0.001). In female participants, strongest factor upon kidney dysfunction was smoking (1.27 [1.16-1.39], P < 0.001). The second strongest factor on kidney deterioration was new-onset proteinuria (1.26 [1.17 1.36], P < 0.001). To reveal the relationship of effects from new-onset proteinuria and smoking on the kidney function, the participants were divided into four groups with and without new-onset proteinuria and smoking. The group with both proteinuria and smoking had significantly worst renal prognosis (P for trend < 0.001). CONCLUSION: Large longitudinal observation study revealed smoking has an evil effect on the progression of CKD. This evil effect could be observed in CKD patients with proteinuria as well as in general population without new-onset proteinuria.

Urinary podocyte markers of disease activity, therapeutic efficacy, and long-term outcomes in acute and chronic kidney diseases.

A critical degree of podocyte depletion causes glomerulosclerosis, and persistent podocyte loss in glomerular diseases drives the progression to end-stage kidney disease. The extent of podocyte injury at a point in time can be histologically assessed by measuring podocyte number, size, and density ("Biopsy podometrics"). However, repeated invasive renal biopsies are associated with increased risk and cost. A noninvasive method for assessing podocyte injury and depletion is required. Albuminuria and proteinuria do not always correlate with disease activity. Podocytes are located on the urinary space side of the glomerular basement membrane, and as they undergo stress or detach, their products can be identified in urine. This raises the possibility that urinary podocyte products can serve as clinically useful markers for monitoring glomerular disease activity and progression ("Urinary podometrics"). We previously reported that urinary sediment podocyte mRNA reflects disease activity in both animal models and human glomerular diseases. This includes diabetes and hypertension which together account for 60% of new-onset dialysis induction patients. Improving approaches to preventing progression is an urgent priority for the renal community. Sufficient evidence now exists to indicate that monitoring urinary podocyte markers could serve as a useful adjunctive strategy for determining the level of current disease activity and response to therapy in progressive glomerular diseases.

Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis.

BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. METHODS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. RESULTS: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. CONCLUSIONS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

A case of primary aldosteronism with excessive secretion of renin that was unmasked by kidney transplantation.

A 42-year-old man showed marked hypokalemia after kidney transplantation. He was diagnosed with hypertension and suffered from acute myocardial infarction at 33 and 38 years of age. At 40 years of age, hemodialysis was introduced. A left adrenal tumor was noted and suspected as a non-functional adrenal adenoma at that time. Therefore, he received a living-donor kidney transplant at 42 years of age. After kidney transplantation, the serum creatinine level dropped. His blood pressure remained high, and the serum potassium level decreased. The PRA and PAC were elevated, and ARR was not elevated. Based on the results of various confirmatory tests and vein sampling, he was diagnosed with excessive secretion of renin from the native kidneys that was complicated by primary aldosteronism (PA), and left nephrectomy and adrenalectomy were performed. The overproduction of aldosterone in the resected adrenal adenoma and over secretion of renin in the kidney with arteriolosclerosis were immunohistologically confirmed. After surgery, the PAC decreased, but the PRA did not decrease. The postoperative serum potassium level improved, and the blood pressure was well controlled with a small dose of medication. This is the first reported case of PA with hyperreninemia after kidney transplantation. It should be noted that PA in dialysis patients and kidney transplant recipients may not fulfill the usual diagnostic criteria of an elevated ARR. In such patients, PA should be suspected based on the absolute value of the PAC and responsiveness to ACTH stimulation, and adrenal and renal vein sampling is required for a definitive diagnosis.

Association of Estimated Total Body Iron with All-Cause Mortality in Japanese Hemodialysis Patients: The Miyazaki Dialysis Cohort Study.

Iron deficiency/excess may be associated with worse prognosis in patients undergoing hemodialysis. This study ascertained the association of the estimated total body iron (TBI) with mortality in patients receiving hemodialysis. Multicenter clinical data collected in the Miyazaki Dialysis Cohort Study from 943 patients receiving hemodialysis were analyzed after stratification into tertile categories by baseline TBI-estimated as the heme iron plus iron storage from ferritin levels. The primary outcome was a 5-year all-cause mortality; hazard ratios of the TBI-all-cause mortality association were estimated using Cox models adjusted for potential confounders, including clinical characteristics, laboratory, and drug data, wherein patients with high TBI were the reference category. The receiver operating characteristic (ROC) curve analyses of TBI, serum ferritin levels, and transferrin saturation were performed to predict all-cause mortality; a total of 232 patients died during the follow-up. The low TBI group (<1.6 g) had significantly higher hazard ratios of mortality than the high TBI group (≥2.0 g). As ROC curve analyses showed, TBI predicted mortality more accurately than either levels of serum ferritin or transferrin saturation. Lower TBI increases the mortality risk of Japanese hemodialysis patients, and further studies should examine whether iron supplementation therapy that avoids low TBI improves prognosis.

Weight Loss Improves Liver Dysfunction and Dipstick Proteinuria in Obesity: The Japan Specific Health Checkups Study.

Introduction: Obesity and inappropriate lifestyle is the major risk factors for liver dysfunction and proteinuria. Nevertheless, previous studies have not described the differential impacts of body weight changes and lifestyle modification on already developed liver dysfunction and proteinuria. Methods: The original cohort was 933,490 individuals from the Japanese general population. In this investigation, we included 36,256 obese individuals with elevated levels of aspartate aminotransferase and/or alanine aminotransferase (≥31 IU/L) or positive proteinuria (+/- or more) in both the first and second years. Outcomes were the first normalization of these data defined as improvement in liver dysfunction and proteinuria. Times to outcomes were assessed using the Cox proportional hazards modeling for -1 kg/m2/year change in body mass index (BMI) changes in exercise and alcohol intake. Results: The multivariable-adjusted hazard ratio (HR) for incident improvement in liver dysfunction with BMI change -1.0 kg/m2/year was 1.07 (95% confidence interval [CI] 1.05-1.09) in obesity and that with improved proteinuria was 1.04 (95%CI 1.02-1.07). Compared to subjects without exercise habits, subjects who gained exercise habits exhibited a higher rate of improvement in liver dysfunction (HR 1.08; 95%CI 1.01-1.15) but not in proteinuria (HR 0.98; 95%CI 0.88-1.08). Compared to subjects with continuous alcohol intake habits, subjects who quit alcohol intake also showed a higher rate of improvement in liver dysfunction (HR 1.20; 95%CI 1.09-1.32). Conclusions: This study suggested that weight loss greater than 1 kg/m2/year improves liver dysfunction and dipstick proteinuria in obesity. Particularly, liver dysfunction can be remedied by acquiring an exercise habit and quitting alcohol intake.

Synergistic effect of proteinuria on dipstick hematuria-related decline in kidney function: The Japan Specific Health Checkups (J-SHC) Study.

BACKGROUND: The effect of isolated hematuria without proteinuria on kidney function decline, and the modification by the severity of proteinuria in general population are not fully elucidated. METHODS: Participants were included in the Japan Specific Health Checkups Study between 2008 and 2014. The exposure of interest was the frequency of dipstick hematuria during the observation. In each proteinuria frequency category (non-, occasional, persistent), hematuria-related decline in the eGFR rate was examined by analysis of covariance (ANCOVA). eGFR decline trajectories were also assessed using mixed-effects models. RESULTS: Among the 552,951 participants, 146,753 (26.5%) had hematuria, and 56,021 (10.1%) and 8,061 (1.5%) had occasional and persistent proteinuria, respectively. During the median follow-up of 3.0 years, annual change in eGFR decline in participants with hematuria was significantly faster than in those without hematuria (mean [95% confidence interval]: - 0.95 [- 0.98 to - 0.92] vs - 0.86 [- 0.87 to - 0.84] mL/min/1.73 m2/year; P < 0.001). In ANCOVA, the hematuria-related annual eGFR decline rate increased as proteinuria frequency categories increased (differences in annual eGFR decline rate between participants with and without hematuria: 0.08 [0.06 to 0.09] in participants with non-proteinuria category, 0.17 [0.15 to 0.18] in occasional proteinuria category, and 0.68 [0.65 to 0.71] mL/min/1.73 m2/year in persistent proteinuria category; P for interaction < 0.001). Similar results were obtained by the linear mixed-effect model. CONCLUSIONS: Proteinuria has a synergistic effect on dipstick hematuria-related decline in kidney function. Among the general population without proteinuria throughout the observational period, the "isolated hematuria"-related eGFR decline was statistically significant but the difference was small.

Trace proteinuria detected via dipstick test is associated with kidney function decline and new-onset overt proteinuria: the Japan Specific Health Checkups (J-SHC) Study.

BACKGROUND: Microalbuminuria is associated with mortality, cardiovascular disease, and end-stage kidney disease. The association between trace proteinuria (detected via dipstick test) and kidney outcomes is unclear. METHODS: This nationwide longitudinal study used data from the Japan Specific Health Checkups Study conducted during 2008-2014. The frequency of trace proteinuria (detected via dipstick test) during first two visits was used as an exposure variable (TrUP 0/2, no trace proteinuria; TrUP 1/2, detected once; TrUP 2/2, detected twice), and kidney outcomes were evaluated. The association between the frequency of trace proteinuria and incidence of 1.5-fold increase in serum creatinine levels and overt proteinuria was analyzed using Cox regression analysis. Trajectories of estimated glomerular filtration rate (eGFR) were compared using a mixed-effect model. RESULTS: Among 306,317 participants, 3188 and 17,461 developed a 1.5-fold increase in serum creatinine levels and new-onset overt proteinuria, respectively, during the median follow-up period of 36.2 months. The adjusted hazard ratio (HR) and 95% confidence interval (CI) for 1.5-fold increase in serum creatinine level in the TrUP 1/2 and TrUP 2/2 groups, compared to TrUP 0/2 group, were 1.23 (1.07-1.42) and 1.39 (1.01-1.92), respectively, and the adjusted HR (95% CI) for overt proteinuria were 2.94 (2.83-3.06) and 5.14 (4.80-5.51), respectively. The eGFR decline rates in the TrUP 1/2 and TrUP 2/2 groups were higher than that in the TrUP 0/2 group (p for interaction < 0.001). CONCLUSIONS: Trace proteinuria (detected via dipstick test) was associated with subsequent kidney function decline and overt proteinuria in the general population.

The effect of lifestyle on the mortality associated with respiratory diseases in the general population.

Lifestyle factors, including smoking habit, diet, and physical activity, affect the prognosis of various diseases. We elucidated the effect of lifestyle factors and health status on deaths from respiratory diseases in the general Japanese population using data from a community health examination database. Data of the nationwide screening program of the Specific Health Check-up and Guidance System (Tokutei-Kenshin), targeting the general population in Japan, from 2008 to 2010 were analyzed. The underlying causes of death were coded according to the International Classification of Diseases (ICD)-10. The hazard ratios of the incidence of mortality associated with respiratory disease were estimated using the Cox regression model. This study included 664,926 participants aged 40-74 years, who were followed up for 7 years. There were 8051 deaths, including 1263 (15.69%) deaths from respiratory diseases. The independent risk factors of mortality associated with respiratory diseases were male sex, older age, low body mass index, no exercise habit, slow walking speed, no drinking habit, smoking history, history of cerebrovascular diseases, high hemoglobin A1c and uric acid levels, low low-density lipoprotein cholesterol level, and proteinuria. Aging and decline of physical activity are significant risk factors for mortality associated with respiratory diseases, regardless of the smoking status.

Association between height loss and mortality in the general population.

Height loss is caused by osteoporosis, vertebral fractures, disc reduction, postural changes, and kyphosis. Marked long-term height loss is reportedly associated with cardiovascular disease and mortality in the elderly. The present study investigated the relationship between short-term height loss and the risk of mortality using the longitudinal cohort data of the Japan Specific Health Checkup Study (J-SHC). Included individuals were aged 40 years or older and received periodic health checkups in 2008 and 2010. The exposure of interest was height loss over the 2 years, and the outcome was all-cause mortality over subsequent follow up. Cox proportional hazard models were used to examine the association between height loss and all-cause mortality. Of the 222,392 individuals (88,285 men, 134,107 women) included in this study, 1436 died during the observation period (mean 4.8 ± 1.1 years). The subjects were divided into two groups based on a cut-off value of height loss of 0.5 cm over 2 years. The adjusted hazard ratio (95% confidence interval) was 1.26 (1.13-1.41) for exposure to height loss ≥ 0.5 cm compared to height loss < 0.5 cm. Height loss ≥ 0.5 cm correlated significantly with an increased risk of mortality compared to height loss < 0.5 cm in both men and women. Even a small decrease in height over 2 years was associated with the risk of all-cause mortality and might be a helpful marker for stratifying mortality risk.

Height loss is associated with decreased kidney function: The Japan Specific Health Checkups (J-SHC) Study.

AIM: Height loss that occurs with aging is a common phenomenon associated with musculoskeletal abnormalities, such as osteoporosis and sarcopenia. Notably, such height loss is also associated with poor outcomes, including cardiovascular disease and mortality. In this study, we investigated the relationship between height loss and kidney outcome. METHODS: This longitudinal study includes data from the Japan Specific Health Checkups Study from 2008 to 2014. Height loss was estimated using the first three visits (visits 1-3), and kidney outcomes were evaluated using data from the following visits (visit 3 to the last visit). The annual height change for each participant was estimated using mixed-effects model, and participants were divided into five groups according to the quintile of the rate. The association between height change and the incidence of 1.5-fold increase in serum creatinine level from baseline was analyzed using Cox regression analysis. The decline rates of estimated glomerular filtration rate among the groups were compared using a mixed-effects model. RESULTS: In total, 187 682 participants were included in the analyses. The median rate of height change was -0.11 cm/year. The adjusted hazard ratio (95% confidence interval) for 1.5-fold increase in serum creatinine level in participants with the steepest category of height decline (Q1; Quintile 1) was 1.45 (1.26-1.67) compared with the reference (Q4; Quintile 4). The decline of the estimated glomerular filtration rate in Q1 (-1.25 mL/min/1.73 m2 /year) was significantly higher than that of the reference: Q4 (-0.92 mL/min/1.73 m2 /year) (P for interaction <0.001). CONCLUSION: Height loss is associated with a rapid decline in kidney function. Geriatr Gerontol Int 2023; 23: 282-288.

Alcohol Consumption and a Decline in Glomerular Filtration Rate: The Japan Specific Health Checkups Study.

Previous studies have reported conflicting results on the clinical impact of alcohol consumption on the glomerular filtration rate (GFR). This retrospective cohort study aimed to assess the dose-dependent association between alcohol consumption and the slope of the estimated GFR (eGFR) in 304,929 participants aged 40-74 years who underwent annual health checkups in Japan between April 2008 and March 2011. The association between the baseline alcohol consumption and eGFR slope during the median observational period of 1.9 years was assessed using linear mixed-effects models with the random intercept and random slope of time adjusting for clinically relevant factors. In men, rare drinkers and daily drinkers with alcohol consumptions of ≥60 g/day had a significantly larger decline in eGFR than occasional drinkers (difference in multivariable-adjusted eGFR slope with 95% confidence interval (mL/min/1.73 m2/year) of rare, occasional, and daily drinkers with ≤19, 20-39, 40-59, and ≥60 g/day: -0.33 [-0.57, -0.09], 0.00 [reference], -0.06 [-0.39, 0.26], -0.16 [-0.43, 0.12], -0.08 [-0.47, 0.30], and -0.79 [-1.40, -0.17], respectively). In women, only rare drinkers were associated with lower eGFR slopes than occasional drinkers. In conclusion, alcohol consumption was associated with the eGFR slope in an inverse U-shaped fashion in men but not in women.

Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial.

OBJECTIVE: Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab. METHODS: RITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse). RESULTS: Rituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p<0.001. 19/85 (22%) patients in the rituximab group and 31/85 (36%) in the azathioprine group experienced at least one serious adverse event during the treatment period. There were no differences in rates of hypogammaglobulinaemia or infection between groups. CONCLUSIONS: Following induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse. TRIAL REGISTRATION NUMBER: NCT01697267; ClinicalTrials.gov identifier.

A Patient with Mitochondrial Disease on Dialysis with Long-term Follow-up of Cardiomyopathy: An Autopsy Case Report.

A 59-year-old man developed diabetes at 24 years old and underwent hemodialysis at 42 years old. At 54 years old, cardiac dysfunction with left ventricular hypertrophy was detected, followed by complete atrioventricular block at 57 years old. The patient was diagnosed with mitochondrial disease based on a myocardial biopsy and the presence of a mitochondrial DNA mutation (3243A>G). He died of septic shock at 59 years old, and an autopsy confirmed mitochondrial cardiomyopathy. If progressive cardiac hypertrophy and conduction disturbances are observed in patients with diabetes mellitus on long-term hemodialysis, mitochondrial disease needs to be considered.

Elevated Crude Mortality in Obese Chronic Kidney Disease Patients with Loss of Exercise Habit: A Cohort Study of the Japanese General Population.

Objective The relationship between obesity and risk of death in chronic kidney disease (CKD) patients remains controversial. In addition, no clear evidence has been accumulated regarding whether or not exercise improves mortality in CKD patients. Methods The original cohort was based on a Japanese general population of 685,889 people from 40 to 74 years old who had undergone annual specific health checkups. The number of all-cause deaths during follow-up (mean, 4.7 years) in this study was 1,490. Information on walking and exercise habits was obtained by questionnaires. The study population was divided into 4 categories by the combination of CKD and obesity [body mass index (BMI) ≥25.0 kg/m2]. Changes in the BMI and walking and exercise habits were determined by results for the first year and following year. Results Obese CKD patients with weight gain (BMI increase by more than +1.0 kg/m2/year) showed a higher crude mortality (1.32%) than those with a stable BMI (within ±1.0 kg/m2/year; 0.69%). In the obese CKD population, mortality was higher with loss of exercise habits (0.96%) than in those continuously maintaining exercise habits (0.52%). The age- and sex-adjusted hazard ratio for all-cause death was 2.23 in the group with weight gain compared to the group with stable weight (p<0.01) and 2.08 in the group with loss of exercise habits compared to those who maintained exercise habits (p<0.01). Conclusion This observational cohort study suggested that loss of exercise habits as well as weight gain of more than 1 kg/m2/year might worsen all-cause mortality in the obese CKD population.

Effect of Low-Density Lipoprotein Apheresis on Quality of Life in Patients with Diabetes, Proteinuria, and Hypercholesterolemia.

INTRODUCTION: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients' quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. METHODS: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6-12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. RESULTS: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (ß coefficient -6.935, 95% confidence interval, 13.313 to-0.556, p = 0.034). CONCLUSION: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

A Body Shape Index and Aortic Disease-Related Mortality in Japanese General Population.

AIMS: Aortic diseases (ADs), including aortic dissection, aortic aneurysm, and aortic rupture, are fatal, with extremely high mortality rates. A body shape index (ABSI), an anthropometric measure calculated as waist circumference adjusted by height and weight, improves the predictive capacity for mortality. However, whether ABSI is a risk factor for AD-related mortality in the general population remains unclear. METHODS: We used a nationwide database of 630,842 individuals (aged 40-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" between 2008 and 2010. RESULTS: During the follow-up period of 3.8 years, 159 AD-related deaths occurred, including 105 aortic dissections and 54 aortic aneurysm ruptures. The subjects were divided into three groups based on ABSI tertiles. Kaplan-Meier analysis demonstrated that the 3rd tertile (with the highest ABSI) had the greatest risk among the three groups. Multivariate Cox proportional hazard regression analysis demonstrated that ABSI was significantly associated with AD-related death after adjusting for confounding risk factors. Neither waist circumference nor body mass index consistently predicted AD-related death in the multivariate model. The prediction capacity was significantly improved by the addition of ABSI to the confounding risk factors. CONCLUSIONS: We demonstrated for the first time that ABSI, a surrogate marker for abdominal visceral fat tissue, was associated with AD-related deaths in the general population, suggesting the importance of central adiposity in the development of AD.

Chemoprophylaxis against Pneumocystis jirovecii pneumonia in Japanese patients with ANCA-associated vasculitis: An observational study.

OBJECTIVES: This study investigated the current practice of prophylactic treatment against Pneumocystis jirovecii pneumonia (PCP) and its effectiveness in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: This study included 319 patients registered from 53 institutions in Japan and newly diagnosed with AAV. During the 2-year observation period, we examined the frequency of usage, effectiveness and safety of prophylactic drugs against PCP. RESULTS: Most patients received prophylactic drugs against PCP with the initiation of immunosuppressive agents, and >50% of them remained on chemoprophylaxis against PCP at 2 years after. The initial daily dose of oral prednisolone and the proportion of cyclophosphamide administration were higher in patients who received chemoprophylaxis against PCP than in those who did not. PCP occurred in nine patients (3%) and resulted in the death of four. The incidence rate of PCP in patients who received chemoprophylaxis was 1.13/100 patient-years (95% confidence interval, 0.38-2.68) and that in those who did not was 2.74 (1.04-6.02). The incidence rate ratio was 0.41 (0.11-1.53). CONCLUSIONS: The markedly low incidence of PCP may be attributed to the continuous chemoprophylaxis against PCP received by >50% of Japanese patients with AAV, although the effectiveness of chemoprophylaxis against PCP was not statistically confirmed.