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Objective The survival advantage of females over males is lost in dialysis patients in many countries. Japanese female hemodialysis patients, however, have a survival advantage over their male counterparts. This study explored causes of death that contribute to sex differences in all-cause mortality in Japanese dialysis patients. Methods Data from the Japanese Society for Dialysis Therapy registry and National Vital Statistics from 2017 and 2018 were used. Standardized mortality ratios, male-to-female mortality rate ratios, and age-adjusted differences between sexes were calculated for all-cause, cardiovascular, and non-cardiovascular mortality, as well as cause-specific mortality, in dialysis patients and the general population. Results During the 2-year study period, 41,006 and 21,254 deaths occurred in 417,740 and 225,292 patient-years in male and female dialysis patients, respectively. The age-standardized all-cause mortality ratio was 1.21 (95% confidence interval, 1.20-1.23) for male patients compared to female patients. The male-to-female mortality rate ratio for cardiovascular disease was about 1.4 in younger age categories but closer to 1.0 in older age categories. Conversely, the ratio for non-cardiovascular disease was about 1.3 in older age categories but closer to 1.0 in younger age categories. Death from infectious disease, malignancy, and heart failure contributed to 38.4%, 22.7%, and 12.1%, respectively, of the male-to-female difference in all-cause mortality of dialysis patients. Conclusion Low cardiovascular mortality in younger age categories and low non-cardiovascular mortality in older age categories contributed to the survival advantage of female Japanese dialysis patients. Infectious disease was the greatest contributor to sex differences in all-cause mortality.

Objective Treatment of elderly patients with rheumatoid arthritis (RA) has been controversial because they often have serious comorbidities and cannot use methotrexate (MTX). In Japan, golimumab (GLM) 100 mg without MTX is approved. We investigated the effectiveness and safety of GLM in elderly patients with RA. Methods The GLM survival rate was evaluated using the Kaplan-Meier method. Disease activities, laboratory findings, and treatments were evaluated. Patients We enrolled 168 patients with RA in our hospital. Using age ≥75 years old to identify elderly patients, younger (n=111) and elderly (n=57) groups were established. Elderly patients were divided into 2 groups according to the MTX treatment status (with, n=27; without, n=25). Results The GLM survival rates were 80.8% and 82.3% in elderly and younger patients, respectively (p=0.762). At 52 weeks, the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) was improved in elderly patients (4.26 vs. 3.31, p0.001); the Health Assessment Questionnaire Disability Index (HAQ-DI) was unchanged (1.12 vs. 0.88, p=0.694). When elderly patients were compared according to the MTX treatment status, the DAS28-ESR had improved in both groups (with MTX: 3.82 vs. 2.68, p0.001; without MTX: 4.76 vs. 4.25, p=0.026); however, the HAQ-DI had not. The GLM survival rates at 52 weeks were 85% and 76% in patients with and without MTX, respectively. Conclusion In elderly patients with RA, GLM was effective, regardless of MTX treatment status, but it did not affect the HAQ-DI. GLM survival rates were comparable between elderly and younger patients. GLM may be a suitable option for elderly patients with RA who cannot use MTX.

Introduction Decreased serum magnesium levels are associated with mortality and fractures in patients with chronic kidney disease; however, there is no recommendation for Mg intake in these populations. Methods This study used cross-sectional analysis to examine the association between Mg intake and serum Mg levels in patients undergoing hemodialysis. Sixty-one patients were included. Results The daily Mg intake was 185 mg (IQR: 151-203 mg), and serum Mg level was 2.4 mg/dL (IQR: 2.2-2.7 mg/dL). Multiple regression analysis showed that intake of enteral formulation by tube feeding was an independent factor associated with serum Mg level (B = 0.90 [95% confidence interval: 0.61-1.20], p Conclusion These findings may aid in serum Mg level management through diet and enteral formulation in patients undergoing hemodialysis. This article is protected by copyright. All rights reserved.

Background 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. Materials and 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/m

Background Recent clinical reports indicate a correlation between gross hematuria after the coronavirus 2019 (COVID-19) vaccination in patients with glomerulonephritis, especially immunoglobulin A nephropathy (IgAN). Furthermore, healthcare workers in Japan were initially vaccinated with an mRNA vaccine from February 17, 2021, and some of them experienced gross hematuria after receiving the vaccination. Methods We conducted a web-based survey of the councilor members of the Japanese Society of Nephrology (581 members, 382 facilities) to elucidate the relationship between gross hematuria and COVID-19 vaccination. Results In the first survey, 27 cases (female: 22, 81.5%) of gross hematuria were reported after receiving a COVID-19 vaccination. Of them, 19 (70.4%) patients were already diagnosed with IgAN at the occurrence of gross hematuria. Proteinuria appeared in eight of the 14 (57.1%) cases with no proteinuria before vaccination and hematuria in five of the seven (71.4%) cases with no hematuria before vaccination. The second survey revealed that a renal biopsy was performed after vaccination in four cases, all of whom were diagnosed with IgAN. Only one case showed a slightly increased serum creatinine level, and no patients progressed to severe renal dysfunction. Conclusion This study clarified the clinical features of gross hematuria after a COVID-19 vaccination. Because there was no obvious progression to severe renal dysfunction, safety of the COVID-19 vaccination is warranted at least in the protocol of inoculation twice.

Background Hemodialysis (HD) patients are at a high risk of falls and fractures. The amount of physical activity (PA) they perform may be limited by psychosomatic factors associated with fear of falling, leading to frailty progression. This study aimed to clarify the relationship between fear of falling and PA in patients undergoing HD. Methods This cross-sectional study included 46 HD patients. Fear of falling was evaluated using the Modified Falls Efficacy Scale (MFES). A 3-axis accelerometer was used to measure PA, including number of steps; 1 to 1.9 METs = static PA, 2 to 2.9 = light PA, and 3 or more = moderate to vigorous PA (MVPA). We examined correlation of MFES with each type of PA. Factors affecting fear of falling were determined using multiple regression analysis. Results The median MFES was 9.2 (7.4, 10.0). MFES was associated with the number of steps (r = 0.608, p 0.001), light PA (r = 0.421, p = 0.004), and MVPA (r = 0.546, p 0.001). Eighteen participants (39.1%) experienced at least one fall in a year and had lower MFES than the non-fall group (fall group: 7.4 [5.1, 9.0] vs. non-fall group: 9.7 [8.5, 10.0], p 0.001). Multiple regression analysis showed that MFES was independently associated with the number of steps (B = 279.7, 95% confidence interval [CI] = 90.5–469.0, p = 0.005) and MVPA (B = 3.52, 95% CI = 1.14–5.90, p = 0.005), respectively. Conclusions Fear of falling was associated with amount of PA among patients undergoing HD. Interventions that target the fear of falling may be effective in reducing HD patients’ fall risk by enhancing PA.

Background Smoking is a well-established lifestyle risk factor for fractures in the general population, but evidence specific to haemodialysis populations is lacking. This nationwide cohort study used data from the Japanese Society for Dialysis Therapy Renal Data Registry to examine the association between smoking status and fractures. Methods A total of 154 077 patients (64.2% men; mean age 68 years) aged ≥20 years undergoing maintenance haemodialysis thrice weekly at the end of 2016 were followed for 1 year. Among these, 19 004 (12.3%) patients were current smokers. Standardized incidence rate ratios of hospitalization due to any fracture were calculated and analysed by multivariable logistic regression analysis, controlling for potential confounders. Propensity score (PS) matching and subgroup analyses were also performed as sensitivity analyses. Results During the 1-year follow-up period, 3337 fractures requiring hospitalization (1201 hip, 479 vertebral and 1657 other fractures) occurred in 3291 patients. The age- and sex-standardized incidence ratio for current smokers was 1.24 (95% confidence interval 1.12–1.39) relative to non-smokers. Standardized incidence ratios were similar after stratification by age group and sex. Multivariable logistic regression analysis revealed a 1.25-fold higher risk of any fracture requiring hospitalization (95% confidence interval 1.10–1.42) in current smokers relative to non-smokers in a fully adjusted model. PS matching showed similar results (odds ratio 1.25; 95% confidence interval 1.05–1.48). Subgroup analyses for baseline covariates revealed no significant interactions. Conclusions Smoking is a significant risk factor for any fracture requiring hospitalization in haemodialysis patients.

Dyslipidemias are common among patients with chronic kidney disease (CKD) and are a major risk factor for cardiovascular disease. This study aimed to investigate the association between early-stage CKD and new-onset dyslipidemia for each lipid profile.This nationwide longitudinal study included data from the Japan Specific Health Checkups (J-SHC) Study. New-onset dyslipidemia was indicated by hypertriglyceridemia (High-TG; ≥150 mg/dL), hyper-LDL cholesterolemia (High-LDL-C; ≥140 mg/dL), or hypo-HDL chelesterolemia (Low-HDL-C;40 mg/dL) levels according to the guideline of Japan Atherosclerosis Society, or High-TG/HDL-C ratio (≥3.5) which was a good predictor of atherosclerosis. The incidence of new-onset dyslipidemia was compared between participants with and without CKD. Survival curves were used to analyze the incidence of each dyslipidemia.Of 289,462 participants with a median follow-up period of 3 years, the incidence of High-TG, High-LDL-C, Low-HDL-C, and High-TG/HDL-C ratios were 64.4/1000 person-years, 83.1/1000 person-years, 14.5/1000 person-years, and 39.6/1000 person-years, respectively. The adjusted hazard ratios (95% confidence intervals) for High-TG, High-LDL-C, Low-HDL-C, and High-TG/HDL-C ratio were 1.09 (1.05-1.13), 0.99 (0.95-1.04), 1.12 (1.05-1.18), and 1.14 (1.09-1.18), respectively, in CKD participants as compared to non-CKD participants. Decreased eGFR and presence of proteinuria were independently associated with higher risks for new-onset of High-TG, Low-HDL-C, and High-TG/HDL-C ratios.CKD was associated with a higher risk of new-onset High-TG, Low-HDL-C, and High-TG/HDL-C ratios, but not High-LDL-C, in the general population. These CKD-specific lipid abnormalities may explain the residual risk for CKD-related cardiovascular disease.

BACKGROUND: Chronic kidney disease (CKD) impairs the anti-inflammatory effects of high-density lipoprotein (HDL) and increases cardiovascular mortality. Though the potential role of dietary interventions to manage HDL is well studied, the clinical trials aimed to increase HDL levels have failed to reduce cardiovascular risk, rendering HDL function to be explored as a more relevant clinical parameter. This study investigates the effects of rice endosperm protein (REP), a plant-based protein, on the anti-inflammatory properties of HDL and renal injury-driven atherosclerosis in comparison with casein, an animal protein. MATERIALS AND METHODS: Ten-week-old apolipoprotein E-deficient hyperlipidemic mice underwent uninephrectomy. The mice (n = 6 each) were pair-fed a normal casein-based diet or a REP-based diet (both with 20.0% protein content) for seven weeks. Atherosclerotic lesions were detected by en face Sudan IV staining of the aorta. RESULTS: The number and sizes of the atherosclerotic lesions were significantly lower in the REP-based diet-fed group than the casein-based diet-fed group (p = 0.038). However, the REP-based diet neither elicited an ameliorative effect on kidney function or histology nor impacted the cholesterol profiles. Furthermore, HDL from the REP-based diet-fed mice significantly suppressed the inflammatory cytokine response of human umbilical vein endothelial cells than that from the casein-based diet-fed mice (MCP-1, p = 0.010; IL-6, p = 0.011; IL-1β, p = 0.028). CONCLUSIONS: The REP-based diet has a higher potential to lessen the atherosclerotic lesions accelerated by renal mass reduction than a casein-based diet, which could be associated with the anti-inflammatory effects of HDL.

Wakamatsu T., Iwasaki Y., Yamamoto S., et al. Type I Angiotensin II Receptor Blockade Reduces Uremia-Induced Deterioration of Bone Material Properties. Journal of Bone and Mineral Research, 36, 1, 67. https://doi.org/10.1002/jbmr.4159., Chronic kidney disease (CKD) is associated with a high incidence of fractures. However, the pathophysiology of this disease is not fully understood, and limited therapeutic interventions are available. This study aimed to determine the impact of type 1 angiotensin II receptor blockade (AT-1RB) on preventing CKD-related fragility fractures and elucidate its pharmacological mechanisms. AT-1RB use was associated with a lower risk of hospitalization due to fractures in 3276 patients undergoing maintenance hemodialysis. In nephrectomized rats, administration of olmesartan suppressed osteocyte apoptosis, skeletal pentosidine accumulation, and apatite disorientation, and partially inhibited the progression of the bone elastic mechanical properties, while the bone mass was unchanged. Olmesartan suppressed angiotensin II-dependent oxidation stress and apoptosis in primary cultured osteocytes in vitro. In conclusion, angiotensin II-dependent intraskeletal oxidation stress deteriorated the bone elastic mechanical properties by promoting osteocyte apoptosis and pentosidine accumulation. Thus, AT-1RB contributes to the underlying pathogenesis of abnormal bone quality in the setting of CKD, possibly by oxidative stress. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Though elimination of obesity is one of main therapeutic goal for lifestyle-related diseases, the impact of appropriate weight loss on reduction of the incidence of proteinuria in the general population is still unclear. The study cohort was based on a general population of 9,33,490 from 40 to 74 years of age who had undergone annual specific health checkups. The subjects who were finally included were the 2,74,598 people for whom all the data necessary for this study were available. The incidence of proteinuria in this study was defined as negative proteinuria at the primary and secondary survey years, and newly developed proteinuria during subsequent follow-up years. Whereas people with rapidly decreased weight tended to have a high incidence of proteinuria in the underweight (BMI

Objective Results from previous studies on the dose-dependent effect of adhering to multiple lifestyle factors on all-cause mortality in patients with chronic kidney disease (CKD) are inconsistent, despite the reported dose-dependent effect in the general population. This study aimed to examine whether CKD modifies the dose-dependent effect of adhering to multiple lifestyle factors on mortality. Methods This population-based prospective cohort study targeted 262,011 men and women aged 40-74 years at baseline. Of these, 18.5% had CKD, which was defined as GFR

Background Locomotive syndrome (LS) is defined as impairment of mobility function. This study aimed to clarify LS and its association with quality of life in hemodialysis patients. Methods This is a cross-sectional study. The subjects were chronic kidney disease patients undergoing maintenance hemodialysis treatment. LS was assessed using two physical tests (two-step test, stand-up test) and one self-reported test (Geriatric Locomotive Function Scale-25). LS has two stages of severity; the beginning of the decline in mobility function is known as Locomo stage 1, and the progression of the decline of mobility function is known as Locomo stage 2. We used SF-36 to assess quality of life and examined their relationships with the Locomo stages. Chi-square test, Kruskal-Wallis test, Jonckheere-Terpstra test, and Mantel-Haenszel test were used for analysis. Multiple linear regression was used to model the cross-sectional association of Locomo stages with each component and summary score of SF-36. Results A total of 76 hemodialysis patients were included. The number of subjects with Locomo stage 1 and stage 2 were 19 (25%) and 53 (70%), respectively, while only four (5%) subjects did not have mobility dysfunction. Each component and summary score of the SF-36 for physical function, role emotional, physical component summary, and mental component summary were significantly associated with Locomo stages. Conclusion A high prevalence and severity of LS in hemodialysis patients was found, and the severity was associated with quality of life.

Objective To evaluate the effectiveness and drug retention rate of golimumab (GLM) for long-term use in daily practice for patients with rheumatoid arthritis (RA). Methods Patients with RA who started GLM therapy with a minimum follow-up period of 52 weeks were included. The patients were divided into a biologic-naive group and switch group. The disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) (DAS28-ESR), grip power, and Japanese version of the health assessment questionnaire (J-HAQ) score were assessed. In addition, the treatment continuation rate was evaluated at the final follow-up. Patients Sixty-five patients (58 women and 7 men; median [range] age, 69 [61-74] years; median [range] disease duration, 9 [5-16] years) were included. Twenty-eight patients were biologic-naive (naive group), and 37 were switched to biologics (switch group). Results The median (range) follow-up period was 134 (58-162) weeks. The DAS28-ESR improved from a median (range) of 4.31 (3.52-5.25) to 2.65 (2.28-3.77) in the naive group and from 4.27 (3.19-4.89) to 2.89 (2.49-3.88) in the switch group. The grip power improved in both groups (p

Factors affecting decline in renal function and cyst growth in patients with autosomal polycystic kidney disease (ADPKD) are not fully described, particularly in Japan. This was the first multi-facility, prospective, observational cohort study conducted in ADPKD patients at 14 centers in Japan. Patients in the J-PKD registry were assessed from December 2009 to June 2012 (follow-up until June 2017). Patients’ data including estimated glomerular filtration rate (eGFR) and total kidney volume (TKV) were assessed initially and a maximum of five times annually. Contributing factors to eGFR decline and TKV growth were identified using multiple linear regression analysis. Of the 340 patients in the J-PKD registry, data analysis was performed for 192 patients in whom serial changes for both eGFR and TKV were obtained. eGFR slope, eGFR change, and TKV change values were as follows: − 2.7 (− 4.2 to − 1.5) (ml/min/1.73 m2/year), − 5.0 (− 9.6 to − 2.3) (%/year), and 4.78 (0.86–8.22) (%/year), respectively. Lower high-density lipoprotein (HDL) cholesterol was an independent predictor of eGFR decline, using both eGFR slope and change (P = 0.04, P = 0.02, respectively), whereas lower hemoglobin and higher uric acid were significantly associated with greater eGFR change only (P = 0.02, P = 0.002, respectively). Younger age and higher fasting blood sugar were independent predictors of greater TKV change (P = 0.01, P = 0.02, respectively). This real-world study in Japan identified risk factors for renal function decline in ADPKD patients. These included lower HDL cholesterol, lower hemoglobin and higher uric acid for eGFR decline, and youth and higher blood sugar levels for TKV growth.

Hyperuricaemia is a risk for premature death. This study evaluated the burden of hyperuricaemia (serum urate > 7 mg/dL) for all-cause and cardiovascular mortality in 515,979 health checkup participants using an index of population attributable fraction (PAF). Prevalence of hyperuricaemia at baseline was 10.8% in total subjects (21.8% for men and 2.5% for women). During 9-year follow-up, 5952 deaths were noted, including 1164 cardiovascular deaths. In the Cox proportional hazard analysis adjusted for confounding factors, hyperuricaemia was independently associated with all-cause and cardiovascular mortality (adjusted hazard ratios [95% confidence interval]; 1.36 [1.25–1.49] and 1.69 [1.41–2.01], respectively). Adjusted PAFs of hyperuricaemia for all-cause and cardiovascular deaths were 2.9% and 4.4% (approximately 1 in 34 all-cause deaths and 1 in 23 cardiovascular deaths), respectively. In the subgroup analysis, the association between hyperuricaemia and death was stronger in men, smokers, and subjects with renal insufficiency. Adjusted PAFs for all-cause and cardiovascular deaths were 5.3% and 8.1% in men; 5.8% and 7.5% in smokers; and 5.5% and 7.3% in subjects with renal insufficiency. These results disclosed that a substantial number of all-cause and cardiovascular deaths were statistically relevant to hyperuricaemia in the community-based population, especially men, smokers, and subjects with renal insufficiency.

Angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are prescribed as conservative or adjunctive therapies for adult idiopathic nephrotic syndrome. However, studies on real‐world practice patterns are scarce. This study aimed to examine the prevalence and incidence of ACEI/ARB prescription and their associated factors. This nationwide cohort study included adult Japanese patients with idiopathic nephrotic syndrome including minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and others. The outcomes were the prevalence of ACEI/ARB prescription at baseline (date of renal biopsy or date of immunosuppressant initiation) and at 2 months after baseline. Of the 326 eligible patients, 122 (37.4%) had already been prescribed ACEIs/ARBs. Of the remaining 204 patients, 67 (32.7%) were newly prescribed within the 2‐month period. MN/FSGS (vs. MCD, adjusted odds ratio [AOR]: 4.96 [95% confidence interval {CI} 2.53–9.72] and 3.95 [95% CI 1.61–9.66], respectively), higher age (per 1‐yr increase, AOR: 1.02 [95% CI 1.00–1.04]), other hypertensive agents (AOR: 2.18 [95% CI 1.21–3.92]), antidiabetic drug (AOR: 6.57 [95% CI 1.77–24.4]) were associated with a higher prevalence of ACEI/ARB prescription. MN (vs. MCD, AOR: 6.00 [95% CI 2.57–14.0]) and higher baseline systolic blood pressure (SBP) (per 10‐mmHg increase, AOR: 1.36 [95% CI 1.09–1.70]) were associated with a higher incidence of ACEI/ARB prescription. On average, incidence of ACEI/ARB prescription increased from 19.2% to 40.8% as baseline SBP increased from 100 to 140 mmHg. Thus, Japanese nephrologists are likely to prescribe ACEIs/ARBs for nephrotic patients with MN or high baseline SBP, even below the hypertensive range.

Introduction Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used in patients with type 2 diabetes mellitus (T2DM) on maintenance hemodialysis (HD), but the efficacy of the once-weekly DPP4 inhibitor omarigliptin is not known. Methods This prospective, randomized, open-label, parallel-group, non-inferiority/superiority, once-daily DPP4 inhibitor linagliptin-controlled, multicenter study examined glycemic control and safety of omarigliptin (UMIN000024284). Sample size was calculated to confirm non-inferiority in terms of changes in glycated hemoglobin (HbA1c). We enrolled 33 patients with T2DM on maintenance HD who had been treated with linagliptin for at least 3 months. The patients were randomized to receive omarigliptin (12.5 mg/week; n = 16) or linagliptin (5 mg/day; n = 17). Primary endpoints were changes in HbA1c and glycoalbumin (GA) over 24 weeks. Results Differences in the mean change in primary endpoint values between the omarigliptin and linagliptin groups were − 0.61% [− 1.14, − 0.09] for HbA1c, with a two-tailed upper 95% limit (i.e., one-tailed 97.5% upper limit) of 0.25%, below the non-inferiority limit, and − 1.67% [− 4.23, + 0.88] for GA, with a two-tailed upper 95% limit of 0.75%, above the non-inferiority limit. At 24 weeks, the omarigliptin group showed significantly greater reduction in HbA1c than the linagliptin group (− 0.2% ± 0.6% vs. 0.4% ± 0.8%, two-tailed p = 0.024) and significantly greater reduction in blood glucose after a single HD session (− 18.4 ± 31.4 mg/dL vs. 25.2 ± 59.5 mg/dL, respectively, two-tailed p = 0.019). No subjects in the omarigliptin group developed hypoglycemia. Conclusions Our data showed that omarigliptin was non-inferior to linagliptin in glycemic control. Omarigliptin is feasible for glycemic control in patients with T2DM on maintenance HD. Clinical Trials Registration UMIN000024284. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-020-00991-y.

A 48-year-old woman with a 9-year-history of anorexia nervosa (AN) was admitted complaining of generalized bone pain. Blood tests showed hypocalcemia and hyperphosphatasemia, and a radiological survey revealed multiple rib fractures, suggesting complication with osteomalacia. Two years earlier, she had undergone subtotal colectomy for colon cancer. Her serum 25-hydroxy vitamin D concentration was below the detectable level. In addition to a poor nutritional intake and insufficient sun exposure, malabsorption of fat-soluble substances in the intestine and phosphate loss from the kidneys might have contributed to the development of her osteomalacia.

Aim We evaluated several sarcopenia-related hormones, cytokines and uremic toxins to identify the humoral factors associated with sarcopenia and frailty in Japanese hemodialysis patients. Methods Twenty Japanese patients aged ≥65 years who underwent maintenance hemodialysis therapy at Uonuma Kikan Hospital for more than 6 months were included in this retrospective cross-sectional study. Clinical data, including physical function and mental state, were obtained from the clinical records collected during the regular evaluation at the beginning of each hemodialysis therapy session, 3 days after the previous hemodialysis therapy. The diagnosis of sarcopenia and frailty was based on the Asian Working Group for Sarcopenia 2019 and the Japanese version of the Cardiovascular Health Study, respectively. The mental state of patients was evaluated using the Japanese version of the Patient Health Questionnaire 9 (J-PHQ-9). Results In univariate analyses, plasma brain-derived neurotrophic factor (BDNF) levels were significantly lower in patients with severe sarcopenia and frailty. The plasma BDNF concentration was correlated with muscle strength and physical performances, such as the 6-m walk test, Short Physical Performance Battery and 5-time chair stand test. BDNF was also correlated with body weight, hemodialysis vintage, and serum levels of total protein and indoxyl sulfate but not with body mass index, appendicular skeletal muscle mass, serum interleukin 6 levels, or J-PHQ-9 scores. The odds ratio per 100 pg/mL of BDNF for the prevalence of frailty was 0.353. Conclusions BDNF is associated with decreased physical performance and the prevalence of severe sarcopenia and frailty in Japanese maintenance hemodialysis patients. Geriatr Gerontol Int 2021; 21: 27-33.

Objective In Japan, the Specific Health Check and Guidance (Tokutei-Kenshin) program was started in 2008 to decrease the social burden related to metabolic syndrome (MetS). However, so far this program has not been found to have any impact on the mortality rate. Methods The subjects consisted of individuals who participated in the Tokutei-Kenshin in seven districts between 2008 and 2015. Using a National database of death certificates, we identified those who might have died and then further confirmed such deaths with the collaboration of the regional National Health Insurance agency and public health nurses. The diagnosis of MetS was made according to the Japanese criteria. The causes of death were classified by ICD-10. Mortality risk was evaluated after adjusting for age, sex, smoking, alcohol intake and past medical history such as stroke, heart disease and kidney disease. Results Among the total of 664,926 subjects, we identified 8,051 fatal cases by the end of 2015. The crude death rate was 1.6% for those with MetS, 1.3% for those with preliminary metabolic syndrome, and 1.1% those without MetS. In MetS, the adjusted hazard ratio (95% confidence interval) was 1.08 (1.02-1.15) for all-cause and 1.39 (1.22-1.58) for cardiovascular disease mortality when the reference was for those without MetS. Conclusion The death rate was found to be significantly higher among the participants with MetS.

The incidence of localized periosteal thickening (LPT, also termed beaking) of the lateral cortex that often precedes an atypical femoral fracture (AFF) was not high in patients with rheumatoid arthritis (RA) but incomplete AFFs developed in two patients. Higher-dose prednisolone was a significant risk factor for LPT in patients with RA. Atypical femoral fractures (AFFs) are stress fractures; bisphosphonate (BP) use is a major risk factor for the development of such fractures. Localized periosteal thickening (LPT, also termed beaking) of the lateral cortex often precedes a complete or incomplete AFF. We evaluated the incidence of latent LPT in patients with rheumatoid arthritis (RA), to evaluate LPT progression, and to define LPT risk factors. A total of 254 patients with RA were included; all underwent annual X-ray evaluation, dual-energy X-ray absorptiometry, and analyses of serum and bone metabolic markers for 2–3 years. LPT of the lateral cortex was sought in femoral X-rays. The incidence of LPT was 2.4% (6/254). Among patients on both BP and prednisolone (PSL) at enrollment, the incidence was 2.3% (3/131). Two femurs of two patients with LPT developed incomplete AFFs; LPT was extensive and associated with endosteal thickening. One patient had been on BP and PSL and microscopic polyangiitis was comorbidity. The other was on a selective estrogen receptor modulator and PSL. A daily PSL dose >5 mg (OR 11.4; 95%CI 2.15–60.2; p = 0.004) and higher-dose methotrexate (OR 1.22; 95%CI 1.01–1.49; p = 0.043) were significant risk factors for LPT. The incidence of latent LPT was not high (2.4%) but incomplete AFFs developed in two RA patients. Higher-dose PSL because of a comorbid disease requiring glucocorticoid treatment other than RA or refractory RA were risk factors for LPT; X-ray screening for latent LPT would usefully prevent complete AFFs.

International audience; Objective: Conflicting findings and knowledge gaps exist regarding links between anemia, physical activity, health-related quality of life (HRQOL), chronic kidney disease (CKD) progression, and mortality in moderate-to-advanced CKD. Using the CKD Outcomes and Practice Patterns Study, we report associations of hemoglobin (Hgb) with HRQOL and physical activity, and associations of Hgb and physical activity with CKD progression and mortality in stage 3-5 nondialysis (ND)-CKD patients. Design and Methods: Prospectively collected data were analyzed from 2,121 ND-CKD stage 3-5 patients, aged ≥18 years, at 43 nephrologist-run US and Brazil CKD Outcomes and Practice Patterns Study–participating clinics. Cross-sectional associations were assessed of Hgb levels with HRQOL and physical activity levels (from validated Kidney Disease Quality of Life Instrument and Rapid Assessment of Physical Activity surveys). CKD progression (first of ≥40% estimated glomerular filtration rate [eGFR] decline, eGFR12 g/dL. Odds of being highly physically active were substantially greater at Hgb>10.5 g/dL. Lower Hgb was strongly associated with greater CKD progression and mortality, even after extensive adjustment. Physical inactivity was strongly associated with greater mortality and weakly associated with CKD progression. Possible residual confounding is a limitation. Conclusion: This multicenter international study provides real-world observational evidence for greater HRQOL, physical activity, lower CKD progression, and greater survival in ND-CKD patients with Hgb levels >12 g/dL, exceeding current treatment guideline recommendations. These findings help inform future studies aimed at understanding the impact of new anemia therapies and physical activity regimens on improving particular dimensions of ND-CKD patient well-being and clinical outcomes.

We report three rheumatoid arthritis (RA) patients with false‐positive procalcitonin (PCT) based on semiquantitative immunochromatography assays without infection, but who had negative PCT assay results based on quantitative methods. Immunochromatography was useful for screening; however, other heterophilic antibodies rather than rheumatoid factor were possible to affect, especially in RA flare.

Background Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan. Methods A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model. Results Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN. Conclusions Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.

Hepcidin, a major regulator of iron metabolism and homeostasis, is regulated by inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis, and the aim of this study was to determine whether serum hepcidin levels are correlated with the degree of osteoporosis in patients with rheumatoid arthritis (RA). A total of 262 patients with RA (67.5 ± 11.4 years; 77.5% female) were enrolled. Serum iron, ferritin, and hepcidin levels were positively correlated each other. Multiple regression analyses revealed that the serum iron level was positively correlated with femoral T and Z scores, whereas the serum hepcidin level was not. Serum hepcidin level was correlated with the serum 25-hydroxy vitamin D level, which was in turn positively related to the femoral Z score. Serum hepcidin and serum iron were indirectly and directly related to osteoporosis in patients with RA.

Background: Evidence for primary prevention of chronic kidney disease (CKD) is insufficient. The population-based prospective Uonuma CKD cohort study aims to explore associations of lifestyle and other risk factors with CKD. We report here the study design and baseline profiles. Methods: All 67,322 residents aged ≥40 years in Minamiuonuma City, Uonuma City, and Yuzawa Town, Niigata Prefecture, Japan and 11,406 participants who attended local health-check examinations were targeted for baseline questionnaire and biochemical sampling, respectively. Information was gathered from 43,217 (64.2%) questionnaires and 8,052 (70.6%) biochemical samples; 6,945 participants consented to both questionnaire and biochemical sampling at baseline, conducted between fiscal years 2012 and 2015. Participants provided information regarding sociodemographic, lifestyle, and self-reported outcomes. Urine albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measured. The primary outcome is CKD based on self-report and biochemical/clinical diagnosis. Results: Mean age of questionnaire respondents was 63.3 (standard deviation [SD], 12.5) years for men and 64.3 (SD, 13.3) years for women. Among participants who submitted urine samples, median ACR was 10.0 (interquartile range [IQR], 5.0–24.0) mg/g for men and 13.0 (IQR, 7.7–27.0) mg/g for women, and median eGFR was 73.6 mL/min/1.73 m2 (IQR, 63.5–84.5) for men and 73.5 mL/min/1.73 m2 (IQR, 64.4–83.5) for women. ACR 30 mg/g or more was found in 1,741 participants (21.7%) and eGFR

Objective The earlobe crease, a wrinkle extending from the tragus to the outer border of the earlobe, is a well-known surrogate marker for a high risk of cardiovascular disease. However, information is lacking about its association with cardiovascular events among hemodialysis patients, who already have an increased risk of cardiovascular disease. We tested the hypothesis that earlobe creases are independently associated with the risk of cardiovascular events among Japanese hemodialysis patients. Methods This prospective cohort study followed 247 adult hemodialysis patients with no history of cardiovascular disease for 4 years. The presence of earlobe creases was defined by two researchers using photos of patients' earlobes on both sides while blinded to one another's assessments and clinical data. The primary outcome was defined as the first fatal or nonfatal cardiovascular event (myocardial infarction, ischemic or hemorrhagic stroke, or peripheral vascular disease requiring aortic or peripheral vascular bypass surgery or below- or above-the-knee amputation). A Fine-Gray competing risks regression model was used to examine the association between earlobe creases and cardiovascular events. Results During the 4-year follow-up period, 43 patients suffered cardiovascular events. After the competing risk of non-cardiovascular death was accounted for, patients with earlobe creases had an increased cumulative incidence of cardiovascular events compared to those without earlobe creases (subhazard ratio =2.04, 95% confidence interval: 1.09 to 3.82). This association was no longer significant after adjusting for age. Conclusion Earlobe creases were not independently associated with cardiovascular events among Japanese hemodialysis patients, suggesting that these marks are simply indicative of advanced age.

Megalin, a proximal tubular endocytosis receptor, is excreted in urine in two forms: ectodomain (A-megalin) and full-length (C-megalin). We explored whether urinary megalin levels can be used as independent prognostic biomarkers in the progression of diabetic kidney disease (DKD).The associations between baseline urinary A-megalin/creatinine (Cr) and/or C-megalin/Cr levels and the subsequent estimated glomerular filtration rate (eGFR) slope were analyzed using a generalized estimating equation. Patients were categorized into higher or lower groups based on the optimal cutoff values, obtained from a receiver operating characteristic curve, of the two forms of urinary megalin.We retrospectively analyzed 188 patients with type 2 diabetes. The eGFR slopes of the higher A-megalin/Cr and higher C-megalin/Cr groups were - 0.904 and -0.749 ml/min/1.73 mUrinary A- and C-megalin/Cr levels are likely to be prognostic biomarkers in the progression of DKD independent of other urinary biomarkers.

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.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.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 3We 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.

Background: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies on this topic have been published. We investigated the association between hypertension/elevated BP and AD in 2 cohorts and conducted a meta-analysis of published prospective studies, including these 2 studies. Methods: We analyzed data from the J-SHC study (Japan-Specific Health Checkups) and UK Biobank, which prospectively followed up 534 378 and 502 424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios and 95% CIs for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks were calculated with random-effects models. A potential nonlinear dose-response relationship between BP and AD was tested with fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined. Results: In the J-SHC study and UK Biobank, there were 84 and 182 ADs during the 4- and 9-year follow-up, and the adjusted hazard ratios of AD were 3.57 (95% CI, 2.17–6.11) and 2.68 (95% CI, 1.78–4.04) in hypertensive individuals, 1.33 (95% CI, 1.05–1.68) and 1.27 (95% CI, 1.11–1.48) per 20–mm Hg increase in systolic BP (SBP), and 1.67 (95% CI, 1.40–2.00) and 1.66 (95% CI, 1.46–1.89) per 10-mm Hg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary relative risks were 3.07 (95% CI, 2.15–4.38, I 2 =76.7%, n=7 studies, 2818 ADs, 4 563 501 participants) for hypertension and 1.39 (95% CI, 1.16–1.66, I 2 =47.7%, n=3) and 1.79 (95% CI: 1.51–2.12, I 2 = 57.0%, n=3) per 20–mm Hg increase in SBP and per 10–mm Hg increase in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mm Hg and DBP >75 mm Hg. Conclusions: Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.

Background Although metabolic syndrome traits are risk factors for chronic kidney disease, few studies have examined their association with urinary biomarkers. Methods Urinary biomarkers, including A-megalin, C-megalin, podocalyxin, albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-D-glucosaminidase, were cross-sectionally assessed in 347 individuals (52.7% men) with a urine albumin-to-creatinine ratio (ACR) Results Participants had a mean body mass index, estimated glomerular filtration rate (eGFR), and median ACR of 23.0 kg/m2, 74.8 mL/min/1.73 m2, and 7.5 mg/g, respectively. In age- and sex-adjusted logistic regression analysis, A-megalin and albumin were significantly associated with the clustering number of metabolic syndrome traits (3 or more). After further adjustment with eGFR, higher quartiles of A-megalin and albumin were each independently associated with the clustering number of metabolic syndrome traits (adjusted odds ratio for A-megalin: 1.30 per quartile, 95% CI 1.03–1.64; albumin: 1.42 per quartile, 95% CI 1.12–1.79). Conclusions Both urinary A-megalin and albumin are associated with the clustering number of metabolic syndrome traits. Further research on urinary A-megalin is warranted to examine its role as a potential marker of kidney damage from metabolic risk factors.

Background Aortic diseases (ADs), including aortic dissection, aortic aneurysm, and aortic rupture, are fatal diseases with extremely high mortality rates. Hypertension has been reported to be associated with AD development; however, it remains unclear whether a 1-year change in diastolic blood pressure (DBP) is a risk factor for AD-related mortality in the general population.Methods and Results:This study used a nationwide database of 235,076 individuals (aged 50-75 years) who participated in the annual "Specific Health Check and Guidance in Japan" for 2 consecutive years between 2008 and 2010. There were 55 AD-related deaths during the follow-up period of 1,770 days. All subjects were divided into 4 groups based on the baseline DBP and change in DBP at 1 year: persistent high DBP, increasing DBP, decreasing DBP, and normal DBP. Kaplan-Meier analysis demonstrated that the persistent high DBP group had the greatest risk among the 4 groups. Multivariate Cox proportional hazard regression analysis demonstrated that both DBP and 1-year change in DBP were significantly associated with AD-related deaths. The prediction capacity was significantly improved by the addition of 1-year change in DBP to confounding risk factors. Conclusions This study demonstrated for the first time that a 1-year change in DBP was associated with AD-related deaths in the general population. Monitoring changes in DBP are of critical importance in the primary prevention of AD-related deaths in apparently healthy subjects aged 50-75 years.

Hypertensive patients are frequently treated with inhibitors of the renin-angiotensin system (RASi). In renin knockout mice, cells programmed for the renin phenotype ( Renin null cells) stimulate the concentric hypertrophy of intrarenal arteries and arterioles. The Renin null cells invade the arteriolar walls and stimulate the concentric growth of smooth muscle cells (SMCs). EM exam showed disorganized glomerular arterioles, marked layering of SMCs and increased basement membrane, compared to a single organized SMC layer in WT mice. The hypertrophy leads to flow obstruction, ischemia, and renal failure.We hypothesize that Renin null cells or renin-expressing cells from animals treated with RASi possess a unique transcriptome that drives their own abnormal fate and the concentric accumulation of SMCs.To test this, we performed single-cell RNA-seq in WT and Renin null cells. We also tested genetically hypertensive mice and their normotensive controls treated with captopril for 6 months. Further, we examined renal biopsies from patients treated with RAS inhibitors for more than 5 years, age-matched controls without RAS inhibitors, and healthy control kidneys.The transcriptional profile of Renin null cells was markedly different from the profile of WT cells. Gene ontology indicated that Renin null cells possess a contractile rather than the endocrine phenotype of WT cells ( p P P P 2 , without RAS; 677.8 ± 313.4 μm 2 , vs. long-term RAS; 1347 ± 529.9 μm 2 , P =0.003).In conclusion, renin cells stimulated by inhibition of RAS have specific molecular programs that contribute to arterial disease.

Background Fabry disease is a progressive X-linked lysosomal disorder. In this subgroup analysis of the global phase III ATTRACT study, the efficacy and safety of oral migalastat, a pharmacologic chaperone, were investigated in Japanese patients with Fabry disease. Methods Patients were randomly assigned to receive migalastat (150 mg every other day) or to continue biweekly enzyme replacement therapy infusions (ERT; agalsidase alfa 0.2 mg/kg or agalsidase beta 1.0 mg/kg) for 18 months followed by a 12-month open-label extension during which all patients received migalastat. End points included glomerular filtration rate (estimated and measured), left ventricular mass index (LVMi), composite clinical outcomes, leukocyte alpha-galactosidase A activity, plasma globotriaosylsphingosine (lyso-Gb3), and safety. Results Data from 7 Japanese patients (migalastat, 5; ERT, 2), mean age 55 years, with high disease burden, were analyzed. All patients in the migalastat group completed the open-label comparison and extension periods. At 18 months, efficacy in the Japanese patient population was similar to that in the overall ATTRACT population. Migalastat treatment increased leukocyte alpha-galactosidase A activity, stabilized renal function, and decreased LVMi. Plasma lyso-Gb3 levels remained low and stable. Additionally, the long-term extension study showed that efficacy of migalastat was maintained for up to 48 months. Migalastat was safe and well tolerated in the Japanese patients, as in the overall ATTRACT population. Conclusion Migalastat can be used to treat Japanese patients with Fabry disease with GLA mutations amenable to migalastat according to the dosage and administration approved in other countries. Trial registration numbers ClinicalTrials.gov, NCT01218659 and NCT02194985.

Although it is widely accepted that the autosomal dominant polycystic kidney disease (ADPKD) patients with large liver cysts have a significant decrement in quality of life (QOL), there is insufficient evidence that clearly demonstrates the relationship between the size of the liver cysts and QOL. Therefore, we started this prospective longitudinal study to investigate the impact of liver cysts on QOL.We grouped the 111 included ADPKD patients into 4 groups (control group A; 25%, group B; 25-49%, group C; 50-75%, group D; 75%) according to liver cysts-parenchyma ratio (CPR). QOL was measured by FANLTC + FACT-Hep scores. We compared QOL scores and several clinical parameters amongst these groups for 3 years.The number of patients in group A, B, C, and D was 31, 14, 14, and 23, respectively. Although there were no significant differences in AST (p = 0.107), ALT (p = 0.925), and serum albumin (p = 0.212) between the four groups, platelet count was significantly decreased along with the extension of cyst volume (p = 0.030). Overall, the mean FANLTC and FACT-Hep scores were 71.8 ± 12.5, and 32.4 ± 5.8, respectively. FANLTC (p = 0.017) and FACT-Hep scores (p = 0.003) were significantly decreased with increasing cyst volume. From the data collected at the time of registration, multivariate linear regression analysis demonstrated that the CPR had a significant influence on FANLTC and FACT-Hep scores.In this cross-sectional and prospective longitudinal study, we demonstrate the relationship between liver cyst volume and QOL in ADPKD patients. We hope to establish the long-term influence on QOL in this ongoing prospective longitudinal study.

OBJECTIVES To analyze the prevalence of systemic de novo thrombotic microangiopathy in ABO-incompatible kidney transplantation and risk factors associated with this condition. METHODS A total of 201 patients who received living-donor kidney transplantation (114 patients with ABO-identical kidney transplantation and 87 patients with ABO-incompatible kidney transplantation) were retrospectively analyzed. Systemic de novo thrombotic microangiopathy was diagnosed clinically according to the presence of thrombocytopenia with microangiopathic hemolytic anemia and pathological findings of thrombotic microangiopathy. Anti-A and anti-B antibodies were purified from human plasma, and these antibodies' bindings to human kidney were investigated in vitro. RESULTS ABO-incompatible kidney transplantation was a significant risk factor of systemic de novo thrombotic microangiopathy (odds ratio 55.9, 95% CI 1.8-8.9, P

Aims: The proper management of atherosclerotic risk factors (ARFs) and attainment of target levels (TLs) for ARFs are crucial in preventing atherosclerotic cardiovascular disease (ASCVD). In this study, utilizing data from the “Specific Health Check and Guidance in Japan,” which was conducted from 2008 to 2011, we examined TL attainment status of low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) and prescription status of dyslipidemia and hypertension in patients with diabetes undergoing medical treatment, and analyzed the factors that affected prescription status. Methods: Subjects receiving medical treatment for diabetes were selected from the database. Subjects were classified by prescription status for dyslipidemia and hypertension, and TL attainment status was assessed for each ARF. Results: The percentage of subjects who did not attain TLs and were not under medication was higher for LDL-C than for BP. The un-prescribed rates among non-TL-attained subjects were 60%–75% for LDL-C, and around 30%–40% for BP. The un-prescribed rates to those who were qualified for prescription therapy were also higher for LDL-C than for BP. Logistic regression analyses revealed that the subjects who were prescribed for dyslipidemia had the following characteristics compared with the un-prescribed non-TL-attained subjects: older age, higher body mass index, lower estimated glomerular filtration rate, previous heart or cerebrovascular disease, and higher medication rate for other ARFs. Conclusions: The present study revealed that, in Japan, the adequate prescription rate for dyslipidemia was lower than that for hypertension in patients with diabetes, suggesting the proper prescription therapy for dyslipidemia should be pursued to further prevent ASCVD.

Positive associations between vitamin D levels and hand grip strength have been reported worldwide, but the results are not consistent and few studies on East Asian populations have been published. The aim of this study was to determine whether such an association is present in a community-dwelling Japanese population, including elderly and middle-aged individuals. This study used a cross-sectional design. Participants were 492 community-dwelling individuals aged ≥ 40 years living in Yuzawa Town, Japan. The health check examination was conducted in 2015, and serum 25-hydroxyvitamin D [25(OH)D, an index of vitamin D levels], and hand grip strength were measured. Covariates were serum albumin concentration, body mass index, and physical activity level. The associations of serum 25(OH)D concentrations with hand grip strength and low grip strength (

A 56-year-old man was referred to our facility after developing edema in his right leg. Enhanced computed tomography (CT) revealed a periarterial soft tissue mass surrounding the right iliac artery compressing the iliac vein. His elevated serum IgG4 level indicated IgG4-related disease (IgG4-RD). Both a percutaneous and surgical biopsy of this periarterial lesion proved challenging and were not pursued. A prostate biopsy, however, finally provided a histological diagnosis of IgG4-RD. Oral steroid therapy successfully resolved his leg edema and periarterial lesion. This case illustrates the usefulness of an alternative prostate biopsy for the histological diagnosis of IgG4-RD when approaching the primary affected lesion is difficult.

Treatment of systemic lupus erythematosus (SLE) often continues with moderate-to-low doses of glucocorticoids for the long term. Bisphosphonates aid in the prevention and management of glucocorticoid-induced osteoporosis (GIOP). However, long-term use of bisphosphonates increases the relative risk of atypical femoral fracture (AFF) and the incidence is typically 16 or 113 per 100,000 person-years in patients treated with bisphosphonates for 5 or 10 years, respectively. Here, we explored bisphosphonate prescription rate and prevalence of AFF in patients with SLE. In total, 270 patients with SLE were enrolled. The Japanese Society for Bone and Mineral Research Guideline 2014 for GIOP management and treatment was used. We also explored AFF history through medical records. Most (n = 251) patients were recommended to treat by the GIOP guideline (scores ≥ 3); bisphosphonates, denosumab, teriparatide, or active vitamin D was prescribed for 85.7%. Bisphosphonates were currently used by 66.1% of the patients, and 65% had used them for ≥ 5 years. Of all patients, 76.7% had a history of bisphosphonate use, 5 of 270 (1.9%) had histories of AFF. Four of five patients with AFF had taken bisphosphonates for ≥ 3.5 years, in addition to moderate doses (≥ 10 mg/day) of glucocorticoids. For the SLE patients with a history of bisphosphonate use, the incidence of AFF was calculated to be 278 per 100,000 person-years. Our single-center study found that bisphosphonates were commonly used long term by Japanese patients with SLE. As AFF is not rare, AFF should be cared in patients with SLE.

Renin‐angiotensin‐aldosterone system inhibitors (RAASi) are recommended for chronic kidney disease (CKD) patients. In this study, we describe RAASi prescription patterns in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, Germany, France, and the United States (US). 5870 patients (mean age 66‐72 years; congestive heart failure [CHF] in 11%‐19%; diabetes in 43%‐54%; serum potassium ≥5 in 20%‐35%) were included. RAASi prescription was more common in Germany (80%) and France (77%) than Brazil (66%) and the United States (52%), where the prevalence of prescription decreases particularly in patients with CKD stage 5. In the multivariable regression model, RAASi prescription was least common in the United States and more common in patients who were younger, had diabetes, hypertension, or less advanced CKD. In conclusion, RAASi prescription patterns vary by country, and by demographic and clinical characteristics. RAASi appear to be underused, even among patients with strong class‐specific recommendations. Although the reasons for this variation could not be fully identified in this cross‐sectional observation, our data indicate that the risk of hyperkalemia may contribute to the underuse of this class of agents in moderate to advanced CKD.

Aim We aimed to describe secular trends in the incidence of end-stage kidney disease (ESKD) requiring renal replacement therapy (RRT) in Japan, and to assess the effect of population aging on the incidence of ESKD. Methods The national incidence of ESKD requiring RRT was calculated using published data and Japan's population statistics. Age-standardized incidence was calculated by direct standardization using the World Standard Population. The average annual percentage of change (APC) in rates and corresponding 95% confidence interval (CI) were computed for trends by joinpoint regression analysis. To assess the effect of population aging on the incidence of ESKD requiring RRT, we used the method proposed by Bashir and Esteve, which splits the crude incidence into three components: population structure, population size, and age-independent risk. Results Age-standardized incidence trends (1983-1996) increased significantly in both men (APC 6.33, 95% CI: 5.39-7.29) and women (APC 5.25, 95% CI: 4.26-6.24). With a significant inflection point in 1996, the trend was stable for men (APC -0.16, 95% CI: -0.48 to 0.17) but significantly decreased for women (APC -1.98, 95% CI: -2.38 to -1.59) from 1996 to 2016. The main reason for the increase in those with ESKD requiring RRT has changed; before 1996, the change in age-independent risk was the main contributor, but after 1996, the change in age structure with a higher proportion of older individuals was the main contributor. Conclusion The increase in number of ESKD patients requiring RRT dramatically changed in Japan during the 1983 to 2016 period.

A 68-year-old man with type 2 diabetes mellitus and chronic hepatitis B infection was referred to the nephrology department before planned surgery for hepatocellular carcinoma. He had been receiving low-dose adefovir dipivoxil (ADV) for 11 years. Laboratory findings revealed impaired re-absorption in the proximal renal tubules. He had been diagnosed with diabetic kidney disease and osteomalacia due to vitamin D deficiency; thus, ADV was not discontinued until he was referred to us. In this case, concomitant diabetes mellitus and vitamin D deficiency might have prevented the early diagnosis of ADV-induced Fanconi syndrome.

Inhibitors of the renin-angiotensin system (RAS) are widely used to treat hypertension. Using mice harboring fluorescent cell lineage tracers, single-cell RNA-Seq, and long-term inhibition of RAS in both mice and humans, we found that deletion of renin or inhibition of the RAS leads to concentric thickening of the intrarenal arteries and arterioles. This severe disease was caused by the multiclonal expansion and transformation of renin cells from a classical endocrine phenotype to a matrix-secretory phenotype: the cells surrounded the vessel walls and induced the accumulation of adjacent smooth muscle cells and extracellular matrix, resulting in blood flow obstruction, focal ischemia, and fibrosis. Ablation of the renin cells via conditional deletion of β1 integrin prevented arteriolar hypertrophy, indicating that renin cells are responsible for vascular disease. Given these findings, prospective morphological studies in humans are necessary to determine the extent of renal vascular damage caused by the widespread use of inhibitors of the RAS.