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Background: Iron deficiency is a major contributor to anaemia in chronic kidney diseases. The association of anaemia and iron deficiency with health-related quality of life in Japanese patients with non-dialysis chronic kidney disease has not been examined. In this study, we evaluated anaemia and iron deficiency in patients with chronic kidney disease G3b-5 and examined their associations with health-related quality of life. Methods: This nationwide cohort study included 2,249 patients with advanced chronic kidney disease receiving nephrologist care from 31 representative facilities throughout Japan; they were randomly selected through stratification by region and facility size and aligned with the Chronic Kidney Disease Outcomes and Practice Patterns Study. Using baseline patient data, we assessed the association of anaemia and iron deficiency with health-related quality of life, employing the 36-item Kidney Disease Quality of Life Questionnaire. Results: The mean mental and physical component summary scores for all patients were 49 and 47, respectively. Patients with haemoglobin levels < 10 g/dL had worse three kidney disease subscale, mental component summary, physical component summary, and subdomain scores than those with haemoglobin levels > 12 g/dL. Patients with absolute iron deficiency (TSAT < 20% and ferritin < 100 ng/mL) had worse three kidney disease subscale and mental component summary scores than those with functional iron deficiency (TSAT < 20% and ferritin ≥ 100 ng/mL). Conclusions: Japanese patients with chronic kidney disease G3b-5 with anaemia or absolute iron deficiency had worse health-related quality of life. Our results provide clinical evidence of renal anaemia in Japan and will be useful for international comparisons. [ABSTRACT FROM AUTHOR]

Introduction: A limited sampling strategy (LSS) for estimating the area under the plasma concentration–time curve (AUC0–12) of the immunosuppressant mycophenolic acid (MPA) is used for therapeutic drug monitoring (TDM) in clinical practice. Our study delves into the applicability of the MPA AUC0–12 LSS, originally developed using particle‐enhanced turbidimetric inhibition immunoassay (PETINIA) measurements, to those obtained via high‐performance liquid chromatography with ultraviolet detection (HPLC–UV). Methods: We developed an LSS for estimating MPA AUC0–12 based on PETINIA measurements in 32 adult kidney transplant patients who were receiving mycophenolate mofetil. Validation of this strategy was conducted in an additional 14 adult kidney transplant patients (validation sets) through measurements obtained by both PETINIA and HPLC–UV. Predictive performance was assessed using mean absolute error (MAE), root mean squared error (RMSE), and "good guess" defined as predicted AUC within observed AUC ± 15%. Results: The three time point equation (0, 2, and 6 h) emerged as optimal for estimating MPA AUC0–12, balancing predictive performance and usefulness in clinical settings. In validation sets, the coefficient of determination for observed versus predicted AUC0–12 was consistent between PETINIA (0.978) and HPLC–UV (0.958) measurements. Comparable MAE, RMSE, and "good guess" outcomes were observed for PETINIA (6.4%, 8.1%, and 85.7%, respectively) and HPLC–UV (7.6%, 9.4%, and 85.7%, respectively) measurements. Conclusion: Our findings support the application of the MPA AUC0–12 LSS, originally developed using PETINIA measurements, to those obtained via HPLC–UV. [ABSTRACT FROM AUTHOR]

Background: Lifestyle modifications by educational sessions are an important component of multidisciplinary treatment for chronic kidney disease (CKD). We attempted to identify the best method to teach these modifications in order to ensure their acceptance by patients and investigated its effectiveness in CKD practice. Methods: This study is a post-hoc analysis of the FROM-J study. Subjects were 876 CKD patients in the advanced care group of the FROM-J study who had received lifestyle modification sessions every 3 months for 3.5 years. Two-hundred and ten males (32.6%) and 89 females (38.2%) showed success in sodium restriction. In this study, we examined factors affecting sodium restriction in these subjects. Results: Subjects received three or more consecutive educational sessions about improvement of salt intake. The median salt-intake improvement maintenance period was 407 days. The number of dietary counseling sessions (OR 1.090, 95%CI: 1.012–1.174) in males and the number of dietary counseling sessions (OR 1.159, 95%CI: 1.019–1.318), CKD stage progression (OR 1.658, 95%CI: 1.177–2.335), and collaboration with a nephrologist (OR 2.060, 95%CI: 1.073–3.956) in females were identified as significant factors improving salt intake. The only factor contributing to the maintenance of improved salt intake was the continuation of dietary counseling (p = 0.013). Conclusion: An increased number of educational sessions was the only successful approach for males to implement and maintain an improved salt intake. Providing the resources for continuous counseling is beneficial for lifestyle modifications and their maintenance in the long-term management of CKD. Continuous counseling for lifestyle modifications is highly cost-effective. Trial registration: The FROM-J study was registered in UMIN000001159 on 16/05/2008. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Sodium‐glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real‐world practice remains unclear. Materials and Methods: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end‐stage kidney disease). Results: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow‐up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin‐angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (β = −0.609, p =.039; β = −2.298, p <.001; β = −0.936, p =.048; β = −0.079, p <.001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p <.001). Conclusions: The concomitant use of renin‐angiotensin system inhibitors and diuretics, higher urine protein levels and pre‐treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes. [ABSTRACT FROM AUTHOR]

Background Unlike systolic blood pressure (SBP), the prognostic value of diastolic blood pressure (DBP) in kidney function has not been established. We hypothesized that pulse pressure (PP), which is associated with arteriosclerosis, would affect the prognostic value of DBP. Methods This longitudinal study used data from the Japan Specific Health Checkups Study was conducted between 2008 and 2014. The participants were stratified into three PP subgroups (low PP ≤39, normal PP 40–59 and high PP ≥60 mmHg). The exposures of interest were SBP and DBP, and the association between SBP/DBP and kidney outcomes (30% decline in the estimated glomerular filtration rate from baseline) was examined in each PP subgroup using a Cox proportional hazards model. Results Among 725 022 participants, 20 414 (2.8%) developed kidney outcomes during a median follow-up period of 34.6 months. Higher SBP was consistently associated with a higher incidence of kidney outcome in all PP subgroups. Although DBP had a positive linear association with the incidence of kidney outcome in low- and normal-PP subgroups, both lower (≤60 mmHg) and higher (≥101 mmHg) DBP were associated with a higher incidence of kidney outcome in the high-PP subgroup, with a U-shaped curve. Hazard ratios (95% confidence intervals) of ≤60 mmHg (reference: 61–80 mmHg in normal-PP subgroup) and ≥101 mmHg were 1.26 (1.15–1.38) and 1.86 (1.62–2.14), respectively. Conclusions In this large population-based cohort, DBP was differently associated with kidney outcome by PP level; lower DBP was significantly associated with a higher incidence of kidney outcome in the high-PP subgroup but not in the low- and normal-PP subgroups. [ABSTRACT FROM AUTHOR]

Understanding the association between compliance to the Chronic Kidney Disease (CKD) guidelines in real-world clinical settings and renal outcomes remains a critical gap in knowledge. A comprehensive analysis was conducted using data from a national, multicenter CKD registry. This study included 4,455 patients with an estimated glomerular filtration rate (eGFR) measurement on the index date and eight additional metrics recorded within six months. These metrics comprised serum electrolyte levels, low-density lipoprotein cholesterol, hemoglobin, and the use of renin-angiotensin system inhibitors. The primary outcome was a composite of renal events, defined by a decline in eGFR to < 15 mL/min/1.73 m2 or a reduction of ≥ 30% in eGFR, confirmed by follow-up tests. Over a median follow-up of 513 days, 838 renal events were observed. High serum potassium levels (> 5.4 mmol/L) were associated with increased event rates compared to lower levels. Similarly, low serum sodium-chloride levels (< 33) correlated with higher event rates. Usage of renin-angiotensin system inhibitors, low serum calcium (< 8.4 mg/dL), and high uric acid levels (> 7.0 mg/dL) were also linked to increased events. Conversely, higher hemoglobin levels (≥ 13 g/dL) were associated with lower event rates. Compliance to guidelines, categorized into quartiles based on the number of met metrics, revealed a significantly reduced risk of events in the highest compliance group (meeting 8 metrics) compared to the lowest (0–5 metrics). Compliance to CKD guidelines in clinical practice is significantly associated with improved renal outcomes, emphasizing the need for guideline-concordant care in the management of CKD. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate nailfold capillary parameters in community-dwelling individuals aged over 60 years who have hypertension and do not exercise regularly. Furthermore, the study examined the correlations between capillary function and other health-related indicators. Design: This study was a single- center pilot trial. Setting: The study took place in the Faculty of Health, Tsukuba University of Technology, Japan. Participants: Hypertensive community-dwelling elderly people took part in the study. Intervention: Microcirculation was observed before and 1 min after an arm-curl exercise by means of capillary microscopy of the non-exercised limb. Additionally, we examined other health-related indicators. Methods: We measured the acute effects of reperfusion on nailfold density, flow, and diameters. Secondary outcomes included the correlations between microvascular parameters and other health-related indicators. We hypothesized that brief exercise could enhance microcirculation reperfusion and correlate with other health-related parameters. Results: There were 20 participants with a mean (SD) age of 67.1 (5.8) years. The capillary flow rate changed from 2.3 ± 6.7 to 2.7 ± 0.2 log µm/s (p < 0.01), and the capillary density changed from 0.8 ± 0.2 to 0.9 ± 0.1 log/mm (p < 0.01), which included a significant increase in the non-exercising limb. Significant correlations were observed between the nailfold capillary diameter and body fat mass, the capillary diameter and physical activity, and the capillary density and bone mineral density. Conclusions: The acute effects of exercise on high-risk elderly individuals can be safe, and even 1 of min exercise can potentially improve their nailfold capillary function, despite the brief time, compared to no exercise. The results indicate that capillaries have an impact on the function of the whole body. Thus, they may be a useful diagnostic tool for assessing nailfold capillaries. [ABSTRACT FROM AUTHOR]

Background: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD. Methods: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed. Results: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002–1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622–0.897; p = 0.004) at a cut-off value of 956.6 pg/mL. Conclusion: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD. Trial registration: UMIN000010806. [ABSTRACT FROM AUTHOR]

In April 2022, an additional medical fee for exercise instruction during haemodialysis treatment was approved for insurance claims in Japan. We conducted a questionnaire survey to investigate the current situation regarding exercise therapy during haemodialysis treatment after this change. Questionnaires were mailed to 4257 haemodialysis facilities, almost all the haemodialysis facilities in Japan, on January 31, 2023. In total, 1657 facilities responded, of which 550 (33%) provided exercise instruction during haemodialysis treatment, and 65% of these claimed the new fee. Of the 550 facilities that had claimed the fee at the time of survey, 245 (55%) started exercise instruction in April 2022 or later. Exercise instruction focused on resistance training (81%) and aerobic exercise (62%) for 20–30 min (66%) three times a week (80%). The instructors included physicians in 45% of facilities, nurses in 74%, and physical therapists in 36%. Efficacy was evaluated in 76% of the facilities providing instruction, mainly by assessing change in muscle strength (49%). Overall, 39% of facilities had experienced some adverse events, but none were life-threatening. In conclusion, after the change in the insurance regime, exercise instruction during haemodialysis treatment has become more popular, and more patients on haemodialysis are undergoing exercise therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) has been associated with increased mortality and cardiovascular events in patients with chronic kidney disease. We hypothesized that the prediction of ESA resistance during ESA administration would be very useful in deciding on a treatment plan. Methods: Patients enrolled in a randomized controlled trial to evaluate renal prognosis in anemic patients with non-dialysis-dependent chronic kidney disease with hyporesponsiveness to ESA were included; the patients had different target hemoglobin levels. A landmark analysis was performed at 3 months into the study. To construct a predictive model for the severe ESA hypo-responder group, in which there was no increase in hemoglobin even with active treatment, background factors and serum test items that affect anemia at study entry were included in a logistic regression model, the area under the curve (AUC) and 95% confidence intervals (CI) were estimated, and sensitivity and specificity were calculated. This study was a post hoc sub-analysis of a randomized controlled trial. Results: The AUC for the 19 existing risk factors as predictors was 0.783 (95% CI: 0.711–0.855). Among the 19 risk factors, the combination of six factors (hemoglobin level, systolic blood pressure, weight, gender, smoking status, and hypertensive retinopathy) with the largest χ2 statistics were selected by multiple logistics regression. The AUC for these 6 predictors was 0.716 (95% CI: 0.634–0.799). To the six existing risk factors, five serum test items that affect anemia (vitamin B12, vitamin B6, folic acid, parathyroid hormone, and 25-hydroxyvitamin D) were added, for a total of 11 risk factors, with a similar AUC of 0.736 (95% CI: 0.655–0.817), sufficient to predict ESA resistance. Conclusions: Our results suggest that existing risk factors and serum test items can be used to predict ESA resistance in patients with non-dialysis-dependent chronic kidney disease on ESA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Fabry disease is an X-linked lysosomal storage disorder caused by insufficient α-galactosidase A (GLA) activity resulting from variants in the GLA gene, which leads to glycosphingolipid accumulation and life-threatening, multi-organ complications. Approximately 50 variants have been reported that cause splicing abnormalities in GLA. Most were found within canonical splice sites, which are highly conserved GT and AG splice acceptor and donor dinucleotides, whereas one-third were located outside canonical splice sites, making it difficult to interpret their pathogenicity. In this study, we aimed to investigate the genetic pathogenicity of variants located in non-canonical splice sites within the GLA gene. Methods: 13 variants, including four deep intronic variants, were selected from the Human Gene Variant Database Professional. We performed an in vitro splicing assay to identify splicing abnormalities in the variants. Results: All candidate non-canonical splice site variants in GLA caused aberrant splicing. Additionally, all but one variant was protein-truncating. The four deep intronic variants generated abnormal transcripts, including a cryptic exon, as well as normal transcripts, with the proportion of each differing in a cell-specific manner. Conclusions: Validation of splicing effects using an in vitro splicing assay is useful for confirming pathogenicity and determining associations with clinical phenotypes. [ABSTRACT FROM AUTHOR]

Inappropriate activation of intrarenal renin–angiotensin system (RAS) may contribute to the pathogenesis of cardio-renal syndrome (CRS). We aimed to examine the cross-sectional associations of urinary angiotensinogen (AGT) excretion, a biomarker of intrarenal RAS activity, with central (aortic) and renal hemodynamic parameters in middle-aged and older adults, including patients with chronic kidney disease. Aortic and renal hemodynamic parameters were measured using applanation tonometry and duplex ultrasonography in 282 participants. Urinary AGT, liver-type fatty acid-binding protein (L-FABP), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured for each participant. Multiple linear regression analyses demonstrated that urinary AGT levels were associated with aortic blood pressures, pulsatile measures of renal blood flow, plasma NT-proBNP and urinary L-FABP levels after adjusting for potential covariates, including age, sex, body mass index, estimated glomerular filtration rate (GFR), and medication use. Additionally, when classified based on GFR stages and urinary AGT levels, plasma NT-proBNP and urinary L-FABP levels increased in participants with lower GFR and higher AGT groups. Our findings suggest that urinary AGT excretion is a shared determinant of central (aortic) and renal hemodynamics in middle-aged and older adults, providing clinical evidence for the potential role of intrarenal RAS activity in the development of CRS. [ABSTRACT FROM AUTHOR]

Background: In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care. Methods: We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR < 60 ml/min from nephrology clinics in Brazil, France, Germany, and the United States (2014–2019). Models were adjusted for CKD stage, country, cardiovascular risk indicators, sex, and age. Results: LLT treatment differed significantly by country, from 51% in Germany to 61% in the US and France (p = 0.002) for statin monotherapy. For ezetimibe with or without statins, the prevalence was 0.3% in Brazil to 9% in France (< 0.001). Compared with patients not taking lipid-lowering therapy, LDL-C was lower among treated patients (p < 0.0001) and differed significantly by country (p < 0.0001). At the patient level, the LDL-C levels and statin prescription did not vary significantly by CKD stage (p = 0.09 LDL-C and p = 0.24 statin use). Between 7—23% of untreated patients in each country had LDL-C ≥ 160 mg/dL. Only 7–17% of nephrologists believed that LDL-C should be < 70 mg/dL. Conclusion: There is substantial variation in practice patterns regarding LLT across countries but not across CKD stages. Treated patients appear to benefit from LDL-C lowering, yet a significant proportion of hyperlipidemia patients under nephrologist care are not receiving treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and objectives: The evident genotype–phenotype correlation shown by the X-linked Alport syndrome warrants the assessment of the impact of identified gene variants on aberrant splicing. We previously reported that single nucleotide variants (SNVs) in the last nucleotide of exons in COL4A5 cause aberrant splicing. It is known that the nucleotides located 2nd and 3rd to the last nucleotides of exons can also play an essential role in the first step of the splicing process. In this study, we aimed to investigate whether SNVs positioned 2nd or 3rd to the last nucleotide of exons in COL4A5 resulted in aberrant splicing. Methods: We selected eight candidate variants: six from the Human Gene Variant Database Professional and two from our cohort. We performed an in-vitro splicing assay and reverse transcription-polymerase chain reaction (RT-PCR) for messenger RNA obtained from patients, if available. Results: The candidate variants were initially classified into the following groups: three nonsense, two missense, and three synonymous variants. Splicing assays and RT-PCR for messenger RNA revealed that six of the eight variants caused aberrant splicing. Four variants, initially classified as non-truncating variants, were found to be truncating ones, which usually show relatively more severe phenotypes. Conclusion: We revealed that exonic SNVs positioned 2nd or 3rd to the last nucleotide of exons in the COL4A5 were responsible for aberrant splicing. The results of our study suggest that attention should be paid when interpreting the pathogenicity of exonic SNVs near the 5′ splice site. [ABSTRACT FROM AUTHOR]

Concomitant with nephrotic syndrome and multicentric castleman's disease (MCD) has only been described in a limited number of small studies and case reports. Among those, none confirmed the renal pathology prior to the onset of MCD, and none of the cases had a history of nephrotic syndrome. A 76 year-old Japanese man visited a nephrologist because of incident nephrotic syndrome. He had previously experienced three episodes of nephrotic syndrome, the last one 13 years ago, and had been diagnosed with membranous nephropathy by renal biopsy. Apart from these previous episodes, he also suffered from systemic lymphadenopathy, anemia, elevated C-reactive protein, polyclonal hypergammopathy, and elevated interleukin (IL)-6. An inguinal lymph node biopsy revealed CD138-positive plasma cells in the interfollicular region. Based on these findings, MCD was diagnosed. Renal biopsy indicated primary membranous nephropathy with spike lesions and bubbling in the basement membranes and deposition of immunoglobulin (Ig) G, IgA, IgM, and phospholipase A2 receptor along the glomerular basement membrane. Corticosteroid monotherapy successfully reduced the edema, proteinuria, and IL-6, but hypoalbuminemia was not sufficiently improved due to castleman's disease and remission of the nephrotic syndrome was not achieved. Later, tocilizumab was administered for remission induction in another facility. To the best of our knowledge, this represents the first report of Castleman's disease with previously diagnosed membranous nephropathy. This case does not provide a causal mechanism for the pathophysiology, but it may be worth suggesting possible involvement of MCD as a trigger for recurrence of membranous nephropathy. [ABSTRACT FROM AUTHOR]

Background: The life prognosis of elderly patients with myeloperoxidase–anti-neutrophil cytoplasmic antibodies-associated vasculitis (MPO-AAV) has been improved by reducing the corticosteroid or cyclophosphamide dose to avoid opportunistic infection. However, many elderly MPO-AAV patients experience recurrence and renal death. An effective and safer maintenance treatment method is necessary to improve the renal prognosis of MPO-AAV. Methods: Patients with MPO-AAV who reached complete or incomplete remission after induction therapy were prospectively and randomly divided into mizoribine (MZR; n = 25) and control (n = 28) groups. The primary endpoint was relapse of MPO-AAV. The patients' serum MZR concentration was measured before (C0) and 3 h after taking the MZR. The maximum drug concentration (Cmax) and the serum MZR concentration curves were determined using population pharmacokinetics parameters. We also assessed the relationship between the MZR concentrations and adverse events. The observation period was 12 months. Results: Fifty-eight MPO-AAV patients from 16 hospitals in Japan were enrolled. Ten patients relapsed (MZR group, n = 6; control group, n = 4; a nonsignificant between-group difference). Changes in the serum MZR concentration could be estimated for 22 of the 25 MZR-treated patients: 2 of the 11 patients who reached a Cmax of 3 μg/mL relapsed, whereas 4 of the 11 patients who did not reach this Cmax relapsed. The treatment of one patient with C0 > 1 μg/mL was discontinued due to adverse events. No serious adverse events occurred. Conclusion: There was no significant difference in the recurrence rate of MPO-AAV between treatment with versus without MZR. [ABSTRACT FROM AUTHOR]

The transtheoretical model (TTM) is a commonly used model of health-related behavioral change. However, the practical effect of using this model for chronic kidney disease (CKD) self-management remains unclear. This study aimed to investigate the association between stages of change for lifestyle behavior and the incidence of CKD in the general Japanese population. A retrospective cohort study was conducted among 178,780 non-CKD participants aged 40–74 years who underwent annual health check-ups for two consecutive years between 2008 and 2009. Health behavior change was determined using questionnaires based on the TTM, which consists of five stages of change (precontemplation, contemplation, preparation, action, and maintenance). The exposure of interest was the change in stages between two years. Participants were categorized into 3 groups 'improved', 'unchanged', or 'deteriorated'. The association between the change in stages and the incidence of CKD was examined using logistic regression analysis. After one year of follow-up, 20.0% of participants developed CKD. Participants in the deteriorated group showed a significantly higher risk of CKD incidence than in the improved group. Promoting the stage of change for healthy lifestyle behaviors evaluated by the TTM was associated with a risk reduction for the incidence of CKD. [ABSTRACT FROM AUTHOR]

Background: The prognosis of lupus nephritis (LN) has improved following the introduction of effective immunosuppressive therapy and progress in supportive care. This study examined recent renal and patient prognosis for adults with LN in Japan. Methods: We conducted a nationwide retrospective cohort study of LN patients who received a renal biopsy between 2007 and 2012 that were registered in the Japan Renal Biopsy Registry. Of 623 registered adults with LN from 25 institutions and their affiliated or community hospitals, 489 were eligible for this study. Results: The median age at renal biopsy was 39 years, and 82.2% of patients were female. Renal biopsies were performed in 348 patients with new-onset LN, 106 with relapse LN, and 35 with refractory LN. The distribution of ISN/RPS 2003 Classes was as follows: I 1.6%; II 5.3%; III (± V) 27.0%; IV (± V) 47.0%; V 18.4%; VI 0.6%. During the median observation period of 63.8 months, 36 patients (7.3%) reached a doubling of serum creatinine or end-stage kidney disease (ESKD), and 28 patients (5.7%) died. The 5 year renal and patient survival rates were 93.9% and 94.7%, respectively. Multivariate analysis revealed body mass index (BMI) and estimated glomerular filtration rate (eGFR) were independent risk factors for a doubling of serum creatinine in ESKD. Age and eGFR were independent risk factors for death. Conclusion: Recent prognosis for adults with LN are relatively good in Japan. Risk factors for impaired renal function are BMI and eGFR at renal biopsy, while age and eGFR are risk factors for death. [ABSTRACT FROM AUTHOR]

Early detection and treatment of diseases through health checkups are effective in improving life expectancy. In this study, we compared the predictive ability for 5-year mortality between two machine learning-based models (gradient boosting decision tree [XGBoost] and neural network) and a conventional logistic regression model in 116,749 health checkup participants. We built prediction models using a training dataset consisting of 85,361 participants in 2008 and evaluated the models using a test dataset consisting of 31,388 participants from 2009 to 2014. The predictive ability was evaluated by the values of the area under the receiver operating characteristic curve (AUC) in the test dataset. The AUC values were 0.811 for XGBoost, 0.774 for neural network, and 0.772 for logistic regression models, indicating that the predictive ability of XGBoost was the highest. The importance rating of each explanatory variable was evaluated using the SHapley Additive exPlanations (SHAP) values, which were similar among these models. This study showed that the machine learning-based model has a higher predictive ability than the conventional logistic regression model and may be useful for risk assessment and health guidance for health checkup participants. [ABSTRACT FROM AUTHOR]

Background: The numbers of patients treated with hemodialysis (HD) in Japan are currently quantified by manual survey. As this method requires much effort from medical institutions and cannot achieve 100% response, a more practical method is required. We aimed to establish a novel method for determining the static and dynamic numbers of patients treated with HD. Methods: This observational study used the national medical billing database (termed NDB) of Japan, based on the records of the universal healthcare insurance system. Medical billing data registered in the NDB between April 2011 and March 2015 were analyzed. From 130 billion records, we extracted and analyzed records of patients who had undergone HD at least once per month. Patients' monthly condition was classified as newly initiated HD, chronic HD, or presumed death, using conditional expressions. We also investigated renal outcome and presumed survival in newly initiated HD patients. Results: In the last month of the study period, 274,100 patients were identified as receiving chronic HD, which is estimated as > 95% of the number of these patients identified in the manual survey so far. The monthly data showed clear seasonality in the incidence of transient HD, which increased in winter and decreased in summer. Conclusion: Analysis of a large national database revealed a significant increase in transient HD in winter and decrease in summer. Applied to additional epidemiological exploratory studies or clinical research, this analytical technique would enable collection of the dynamics of almost all HD patients nationwide. [ABSTRACT FROM AUTHOR]

Background: A recent cost-effectiveness analysis (CEA) study evaluated the widespread diffusion of behaviour modification intervention for patients with chronic kidney disease (CKD). Incorporating this behaviour modification intervention, comprising educational sessions on nutrition/lifestyle and support for regular patient visits, to the current CKD guideline-based practice was found to be cost-effective. This study aimed to examine the affordability of this efficient new practice under the hypothesis that the behaviour modification intervention would be initiated by general physicians (GPs). Methods: A budget impact analysis was conducted by defining the target population as patients aged 40–74 years with stage-3–5 CKD based on the prevalence of definitive CKD in the Japanese general population. Costs expended by social insurers without discount were counted as budgets. We estimated the annual budget impact for 15 years by running our CEA model, assuming that it would be good for the span. Results: We estimated the number of patients with end-stage kidney disease (ESKD) to decrease by 4,496 in the fifteenth year of the new practice using our CEA model. Compared to that in the current practice, the budget impact as total additional expenditure of the new practice was estimated to be negative by the tenth year in the base case. Conclusions: The widespread diffusion of behaviour modification intervention would contain public health care expenditure over the mid-to-long term, resulting from a reduction in progression to ESKD. We suggest that providing sufficient economic incentives to GPs and strengthening recommendations in CKD guidelines would realise effective GP-initiated interventions. [ABSTRACT FROM AUTHOR]

Background: Hyperchloremic metabolic acidosis (HCMA) from renal tubular acidosis (RTA) is common in kidney transplant (KT) recipients. Calcineurin inhibitors (CNIs) are a potential cause of RTA, and whether HCMA is a determinant of poor graft prognosis is controversial. Methods: The subjects were living‐donor KT recipients (LDKTRs, n = 47) and matched donors (n = 43). All cases of rejection, extrarenal causes, and respiratory disorders were excluded. HCMA was defined as having a [Na+]–[Cl−] value of ≤34 or starting alkalization. We determined the potential causes of HCMA in LDKTRs at 3 months (m) and 1 year (y) post‐KT. We examined renal hemodynamic parameters in 26 LDKTRs at 1 y post‐KT: namely, glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF; GFR/RPF) and pre‐/post‐glomerular vascular resistance (pre‐/postVR). Results: The HCMA incidence in the 3‐m post‐KT LDKTR group was higher than that of the donors (51.0% vs. 6.9%, p < 0.001, adjusted odds ratio: 6.7–15.7). Among adjusted factors, the most dominant HCMA contributor was low hemoglobin concentration (Hb ≤ 12 g/dl). Compared to non‐HCMA cases, HCMA patients had low FF and low post‐VR (p = 0.008, 0.003, respectively) suggesting increased intrarenal post‐glomerular blood flow. The high pathological score of alternative arteriolar hyalinosis (aah) ≥2 was a significant HCMA risk. The tacrolimus trough level was not high in HCMA but was significantly high in HCMA in the low post‐VR setting (p = 0.002). Conclusion: Among LDKTRs, low hemoglobin level is an important contributor to the manifestation of HCMA in the induction period, and increased intrarenal post‐glomerular blood flow is a key condition for the development of CNI‐induced RTA. [ABSTRACT FROM AUTHOR]

In Europe, the number of new KRT patients increased at an annual rate of 4.8% (95% CI 4.5% to 5.0%) between 1990 and 1999, but gradually declined after 2000, with a marked reduction of -2.2% in new patients between 2008 and 2011 (95% CI -4.2% to -0.2%) [[4]]. The number of patients requiring kidney replacement therapy (KRT) is increasing worldwide [[1]]. Variations in the incidence of KRT were compared in long-term continuous KRT registries [2019 prevalence in ERA (n = 607 320), USRDS (n = 809 103) and Japan (n = 344 640; dialysis patients only)]. [Extracted from the article]

Background: Dipstick urine tests are a simple and inexpensive method for detecting kidney and urological diseases, such as IgA nephropathy and bladder cancer. The nationwide mass screening program, Specific Health Checkup (SHC), started in Japan in 2008 and targeted all adults between 40 and 74 years of age. Dipstick urine tests for proteinuria and glucosuria are mandatory as part of the SHC, but dipstick urine tests for hematuria are not. However, the dipstick hematuria test is often administered simultaneously with these mandatory tests by some health insurers. Hematuria is common in Japanese general screening participants, particularly elderly women, and the necessity of mass screening using the dipstick hematuria test has been discussed. This study aimed to evaluate the cost-effectiveness of mass screening for dipstick hematuria tests in addition to the SHC. Methods: Using a decision tree and Markov modeling, we conducted a cost-effectiveness analysis from a Japanese societal perspective. Results: Compared with the current SHC, mass screening for dipstick hematuria tests, in addition to the SHC, costs less and gains more, which means cost-saving. Similar findings were observed in the sex-specific analysis. Conclusion: Our results suggest that mandating the dipstick hematuria test could be justifiable as an efficient use of finite healthcare resources. The results have implications for mass screening programs not only in Japan but worldwide. [ABSTRACT FROM AUTHOR]

Background: Patients with end-stage kidney disease (ESKD) face higher risks of life-threatening events including cardiovascular disease. Various risk factors are identified as agents influencing the life prognosis of ESKD patients. Herein, we evaluated the risk factors related to the outcomes of Japanese patients with dialysis induction. We present the study protocol, the patients' baseline characteristics, and their outcomes.Methods: The Ibaraki Dialysis Initiation Cohort (iDIC) Study is a prospective multi-center cohort study in collaboration with 60 tertiary-care facilities in Ibaraki Prefecture, Japan. We collected baseline data from clinical records and analyzed blood and urine samples of these facilities' patients with diabetic nephropathy, hypertensive nephrosclerosis, and chronic glomerulonephritis (CGN). The study's primary outcome was the survival rate at 24 months after dialysis induction. We performed a Kaplan-Meier analysis for cumulative survival and a Cox proportional hazards analysis for all-cause mortality and hospitalization.Results: We analyzed 636 patients' cases (424 males, 212 females, age 67.4 ± 13.1 yrs. [mean ± SD]). We compared the patients' baseline data with those of similar cohort studies. As the primary kidney disease, 327 cases (51.4%) were diagnosed as diabetic nephropathy, 101 (15.9%) as hypertensive nephrosclerosis, and 114 (17.9%) as CGN. The mean serum creatinine value was 9.1 ± 2.9 mg/dL. The mean estimated glomerular filtration rate was 5.6 ± 1.8 mL/min/1.73m2. The cumulative survival rates at 6 months and 24 months after dialysis induction were 95.2 and 87.7%, respectively. The cumulative survival rate was significantly lower with increasing age. A Cox proportional hazards regression analysis demonstrated that high age was significantly associated with all-cause mortality.Conclusions: Regarding the clinical characteristics of these newly induced dialysis patients, the same trend as in other cohort studies was observed. Another study is underway to explore prognostic factors based on the iDIC Study's findings. [ABSTRACT FROM AUTHOR]

Background: Rapidly progressive glomerulonephritis (RPGN) can progress to end-stage kidney disease within a short period. This study is a continuation of the chronological nationwide survey conducted by the Japan-RPGN working group. Methods: We examined a total of 2793 RPGN cases registered during four periods (1989–1998, 1999–2001, 2002–2008, 2009–2011) plus 1386 cases in 2012–2015. As potential prognostic determinants, we investigated the onset period, the clinical severity (CS) grade [classified according to age, serum creatinine (sCr) and C-reactive protein levels, and presence/absence of lung lesions], and causative disease. Results: The cumulative overall RPGN patient survival at 24 months kept improving over the five periods (72.0%, 72.9%, 77.7%, 83.0%, 84.9%, p < 0.001 for trend). The cumulative renal survival also improved in the latest period (68.7%, 75.4%, 76.7%, 73.4%, 78.2%, p < 0.001 for trend). The CS grade was well stratified to predict both life and renal prognoses. Anti-glomerular basement membrane disease (aGBMD)-RPGN had a poorer renal prognosis than other diseases. In anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV-RPGN, accounting for > 70% of the overall RPGN), the prognostic results were similar to that for overall RPGN. There was a much better renal prognosis for the latest period under the condition of sCr < 3 mg/dL (the 24-month cumulative renal survival: 97.9%), but not for sCr ≥ 3 mg/dL (61.5%). Conclusions: In overall RPGN as well as AAV-RPGN, both life and renal prognoses tended to improve, but the favorable renal result was substantially limited to mild cases. There was no improvement of the renal prognosis in aGBMD-RPGN. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: Whereas people with rapidly decreased weight tended to have a high incidence of proteinuria in the underweight (BMI < 18.5 kg/m2) and normal weight (18.5–24.9 kg/m2) groups, the obese group (≥ 25.0 kg/m2) with rapidly decreased weight had a lower incidence compared to those with stable weight. In the obese population, a rapid decline of BMI (− 1 to − 5 kg/m2 per year) was associated with a reduced risk (hazard ratio [95% confidence interval]; 0.89 [0.80–0.98], P = 0.02) of proteinuria. Conclusions: Weight reduction can lead to a risk reduction of 11% in the incidence of proteinuria in obese Japanese adults. This is the first study to report the effects of weight reduction on the early phase of chronic kidney disease in obesity relevant to the characteristics of the Japanese general population. The present findings might have a role in renal health promotion in Japan. [ABSTRACT FROM AUTHOR]

Background: Renal function gradually declines with age. However, the association between changes in renal function and healthy aging has not been determined. This study examined the distribution of estimated glomerular filtration rate (eGFR) values in healthy subjects by age using large-scale cross-sectional data of health check-up participants in Japan. Methods: Among the 394,180 health check-up participants, 75,217 (19.1%) subjects without hypertension, diabetes, hyperlipidemia, obesity, proteinuria, smoking, past history of cardiovascular diseases, and renal failure/not undergoing dialysis were included in the healthy group. The distribution of eGFR values was determined at each age between 39 and 74 years. Results: in healthy subjects, the mean (± 2 SD range) values of eGFR (mL/min/1.73 m2) at ages 40, 50, 60, and 70 were 88.0 (55.4–121.7), 82.3 (51.2–113.3), 77.8 (48.1–107.6), and 72.9 (44.7–101.1), respectively. The difference in the mean eGFR by age was almost constant across all ages. In the linear regression analysis adjusted for sex, the regression coefficient of mean eGFR for a one-year increase in age was -0.46 mL/min/1.73 m2 in healthy subjects (P < 0.001). By sex, the distribution of eGFR and the 1-year change in eGFR showed similar results in both men and women. Conclusions: Renal function slowly declined with age in a healthy population; however, it was relatively preserved until the mid 70 s. This result suggests that a decline in renal function often observed in the elderly does not attribute to aging alone, and further examination might be required to clarify the cause of renal impairment. [ABSTRACT FROM AUTHOR]

Aim: Chronic kidney disease (CKD) is an important public health problem. Recently, CKD has been found to be associated with poor physical functioning in community‐dwelling elderly individuals. However, the physical functioning of non‐dialysis (ND) patients with advanced CKD treated by nephrologists is unknown. Methods: Patients with ND‐CKD stage G3b‐5 who participated in a nationwide Reach‐J CKD cohort study were included in this study. Physical functioning and physical activity were assessed by the Katz Index, Lawton‐Body instrumental activities of daily living (IADL) scale, and Rapid Assessment of Physical Activity questionnaire of the international CKD Outcomes and Practice Patterns Study (CKDopps) questionnaires. Dichotomies between good and poor physical functioning and physical activity scores were explored. Results: Among 1628 patients, 84.3% had good physical functioning. Poor physical functioning was more common with older age (p <.001), higher CKD stage (p <.05), and comorbid conditions such as diabetes (p <.001), cardiovascular disease (p <.05), cerebrovascular disease (p <.001), and cancer (non‐skin) (p <.05). Forty percent of the patients were inactive. Physical inactivity was more common with older age (p <.001) and higher CKD stage (p <.001). Conclusion: A minority, but sizeable proportion of patients with advanced CKD treated by nephrologists in Japan have some disability in ADLs/IADLs. Nephrologists need to routinely assess the physical functioning and physical activity of patients with advanced CKD to provide individualized guidance and comprehensive support to these patients for their daily life. SUMMARY AT A GLANCE: Among non‐dialysis stage G3b‐5 subjects, poor physical functioning was more common with older age, higher CKD stage, and comorbid conditions such as diabetes, cardiovascular disease, cerebrovascular disease, and cancer (non‐skin). The study stressed the need for nephrologists to routinely assess the physical functioning and physical activity of patients with advanced CKD to provide individualized guidance and comprehensive support for their daily life. [ABSTRACT FROM AUTHOR]

Objective: Randomized controlled trials have shown kidney-protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy, as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitor initiation modify treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients, is unknown.Research Design and Methods: Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease.Results: At baseline, mean age at initiation of the SGLT2 inhibitor (n = 1,033) or other glucose-lowering drug (n = 1,033) was 64.4 years, mean eGFR was 68.1 mL/min per 1.73 m2, and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs. other drugs 0.75 mL/min/1.73 m2 per year [0.51 to 1.00]). During a mean follow-up of 24 months, 103 composite kidney outcomes occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26-0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiation of SGLT2 inhibitors (Pheterogeneity ≥ 0.35).Conclusions: The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to examine the cross-sectional associations of sedentary time and physical activity time with bone density in patients with chronic kidney disease (CKD). The isotemporal substitution (IS) modeling was used to estimate the beneficial effects of behavioral changes (e.g., replacing sedentary time with physical activity time) on bone density in these patients. Materials and methods: A total of 92 patients with CKD (age: 65 ± 9 years; estimated glomerular filtration rate: 57 ± 22 mL/min/1.73 m2) were included in this cross-sectional study. The times spent in sedentary behavior (SB), light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were assessed using a triaxial accelerometer. Through quantitative ultrasound measurements, the stiffness index, as a measure of bone density, was calculated using the speed of sound and broadband ultrasound attenuation. Results: In multivariate analyses, the stiffness index was beneficially associated with the MVPA time (β = 0.748), but was not significantly associated with the SB and LPA times. The IS models showed that replacing 10 min/day of SB with the equivalent LPA time was not significantly associated with the stiffness index; however, replacing 10 min/day of SB with the equivalent MVPA time was beneficially associated with the stiffness index (β = 0.804). Conclusion: These results suggest that a small increase in MVPA time (e.g., 10 min/day) may attenuate the decline in bone density in patients with CKD. Our findings may provide insight for the development of novel strategies for improving bone health in patients with CKD. [ABSTRACT FROM AUTHOR]

Background and objectives: Chronic kidney disease (CKD) patients have lower levels of physical function. Especially, leg strength is important for daily living and preventing falls. However, physical function screenings are difficult to perform at clinical sites. To find clinically useful method to evaluate physical function in predialysis CKD patients, we tried to evaluate the relationship between the ratio of serum creatinine to serum cystatin C (Cre/CysC), and knee extensor muscle strength/body weight (KEMS) which reflects their leg strength. Design, setting, participants, and measurements: We recruited 147 outpatients with CKD (87 men; mean age, 61.6 ± 9.8 years; mean eGFRcreat, 40.7 ± 12.9 mL/min/1.73m2) in this cross-sectional study. KEMS was assessed using a wire strain gauge dynamometer. Skeletal muscle mass and body fat mass were assessed by bioelectrical impedance analysis. Results: The mean value of Cre/CysC was 1.01 ± 0.18. The mean value of KEMS was 1.60 ± 0.47 Nm/kg. In multivariate linear regression analysis, skeletal muscle mass (p < 0.01), body fat mass (p < 0.01), hemoglobin (p = 0.01), and Cre/CysC (p < 0.01) was independently related to KEMS. The correlation between Cre/CysC and KEMS is stronger in high quantile of Cre/CysC. Conclusions: In predialysis CKD patients, KEMS showed lower as CKD stage advanced. Cre/CysC is significantly related to KEMS independently. Cre/CysC may be an alternative marker for leg strength in CKD patients and even more valuable to utilize in cases with high Cre/CysC. [ABSTRACT FROM AUTHOR]

Growing evidence has demonstrated an association between nondialysis chronic kidney disease and cancer incidence, although the association between trace proteinuria and cancer death remains unclear. The aim of this study was to investigate the association between trace proteinuria and cancer death in a community-based population in Japan. This was a prospective cohort study of 377,202 adults who participated in the Japanese Specific Health Check and Guidance System from 2008 to 2011. Exposure was dipstick proteinuria categorized as − (negative), ± (trace), 1 + (mild), or ≥ 2 + (moderate to heavy). Outcome was cancer death based on information from the national database of death certificates. Adjusted Cox hazard regression model was used to evaluate the associations between trace proteinuria and cancer death. During median follow-up of 3.7 years, 3056 cancer deaths occurred, corresponding to overall cancer death rate of 21.7/10,000 person-years. In the fully adjusted model, risk of cancer death increased significantly in each successive category of proteinuria: hazard ratio (HR) (95% confidence interval [95% CI]) for risk of cancer death was 1.16 (1.03–1.31), 1.47 (1.27–1.70), and 1.61 (1.33–1.96) for trace, mild, and moderate to heavy proteinuria, respectively. Sensitivity analyses revealed a similar association between trace proteinuria and cancer death, and participants with trace proteinuria had greater risk of mortality from hematological cancers (HR: 1.59 [95% CI: 1.09–2.31]). Both mild to heavy and trace proteinuria were significantly associated with risk of mortality from cancer in a general population. [ABSTRACT FROM AUTHOR]

Background: Disease-specific trajectories of renal function in advanced chronic kidney disease (CKD) are not well defined. Here, we compared these trajectories in the estimated glomerular filtration rate (eGFR) by CKD stages. Methods: Patients with multiple eGFR measurements during the 5-year preregistration period of the REACH-J study were enrolled. Mean annual eGFR declines were calculated from linear mixed effect models with the adjustment variables of baseline CKD stage, age, sex and the current CKD stage and the level of proteinuria (CKDA1-3). Results: Among 1,969 eligible patients with CKDG3b-5, the adjusted eGFR decline (ml/min/1.73 m2/year) was significantly faster in diabetic kidney disease (DKD) patients and polycystic kidney disease (PKD) patients than in patients with other kidney diseases (DKD, − 2.96 ± 0.13; PKD, − 2.82 ± 0.17; and others, − 1.95 ± 0.05, p < 0.01). The declines were faster with higher CKD stages. In DKD patients, the eGFR decline was significantly faster in CKDG5 than CKDG4 (− 4.10 ± 0.18 vs − 2.76 ± 0.20, p < 0.01), while these declines in PKD patients were similar. The eGFR declines in PKD patients were significantly faster than DKD patients in CKDG4 (− 2.92 ± 0.23 vs − 2.76 ± 0.20, p < 0.01) and in CKDA2 (− 3.36 ± 0.35 vs − 1.40 ± 0.26, p < 0.01). Conclusion: Our study revealed the disease-specific annual eGFR declines by CKD stages and the level of proteinuria. Comparing to the other kidney diseases, the declines in PKD patients were getting faster from early stages of CKD. These results suggest the importance of CKD managements in PKD patients from the early stages. [ABSTRACT FROM AUTHOR]

Background: Most data on chronic kidney disease (CKD) prevalence has been based on single measurements of renal function and proteinuria. The aim was to determine the prevalence of CKD diagnosed by chronic proteinuria and/or reduced eGFR in a recent year in Japan. Methods: In the main study, using a population-based cohort in Japan, the overall prevalence of CKD, defined as persistent positive proteinuria and/or eGFR < 60 ml/min/1.73 m2, was determined. Of 2,849,557 persons, 763,104 had data for eGFR and proteinuria in both 2014 and 2015. For estimating number of CKD cases in Japanese adults, a regional cohort data with age ranging 22–87 years (N = 22,037) was further applied to the analysis. Results: Definitive CKD was present in 2.3–23.0% of men and 1.7–17.1% of women age from 40 to 74 years in the main cohort. The estimated prevalence of reduced eGFR and/or proteinuria in the baseline year alone was 15.7% in men and 13.6% in women; the prevalence of definitive CKD was 10.9% in men and 9.2% in women. The number of CKD cases based on a single-year test in Japanese adults over 20 years of age increased from 13.3 million to 14.8 million between 2005 and 2015. Conclusions: Recent changes in prevalence of CKD seem to be mainly caused by an increase in Japan's elderly population. Although past reports may lead to overdiagnosis of CKD by a single-year test, the estimated number of definitive CKD was 10.2 million in 2015. [ABSTRACT FROM AUTHOR]