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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: 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]

Kidney organoids generated from human pluripotent stem cells (hPSCs) have drastically changed the field of stem cell research on human kidneys within a few years. They are self‐organizing multicellular structures that contain nephron components such as glomeruli and renal tubules in most cases, but hPSC‐derived ureteric buds, the progenitors of collecting ducts and ureters, can also form three‐dimensional organoids. Today's challenges facing human kidney organoids are further maturation and anatomical integrity in order to achieve a complete model of the developing kidneys and ultimately a complete adult organ. Since chronic kidney disease (CKD) and impaired kidney function are an increasing burden on public health worldwide, there is an urgent need to develop effective treatments for various renal conditions. In this regard, hPSC‐derived kidney organoids may impact medicine by providing new translational approaches. The unique ability of kidney organoids derived from disease‐specific hPSCs to reproduce human diseases caused by genetic alterations may help provide the next generation of kidney disease models. Recent advances in the field of kidney organoid research have been generally accompanied by progress in developmental biology and other technological breakthroughs. In this review, we consider the current trends in kidney organoid technology, especially focusing on the relationship to the study of human kidney development, and discuss the remaining hurdles and prospects in regenerating human kidney structures beyond organoids. [ABSTRACT FROM AUTHOR]

Several recent clinical trials and meta-analyses have shown that lowering blood pressure reduces the risk of cardiovascular disease. However, current evidence that describes general demographics in blood pressure and mortality with chronic kidney disease is sparse in Japan. Using a population-based longitudinal cohort that received annual health checkups in Japan in 2008, hypertensive status, self-reported use of antihypertensive drugs, and prognosis were examined through 2012. Chronic kidney disease was defined as positive proteinuria or estimated glomerular filtration rate <60 ml/min/1.73 m2. Subjects were 40 to 74 years old (n = 227,204) with median 3.6 years follow-up period, and patients with and without chronic kidney disease were analyzed separately (n = 183,586 and n = 43,618, respectively). Cardiovascular disease mortality, comprising coronary heart diseases and stroke as entered in the national death registry using ICD-10 coding, was examined. Among all subjects, 346 deaths (96 in chronic kidney disease and 250 in non-chronic kidney disease) due to cardiovascular disease occurred. Compared with cardiovascular disease mortality in chronic kidney disease patients with untreated normal blood pressure, the multivariable adjusted hazard ratio was 3.08 (95% confidence interval: 1.75–5.41) for those with untreated hypertension, 2.30 (1.31–4.03) for those who became normotensive after treatment, and 3.28 (1.91–5.64) for those who remained hypertensive despite treatment. In non-chronic kidney disease subjects, the ratios were 1.90 (1.33–5.41), 1.95 (1.35–2.80), and 1.77 (1.18–2.66), respectively. These results from a nationwide cohort could be one of representative demographics of controlling blood pressure and cardiovascular disease deaths when treating patients with chronic kidney disease in Japan in recent years. Even after development and spread of anti-hypertensive drugs, preventing development of hypertension is preferable, because any hypertension treatment status comparing untreated normal blood pressure was a risk of cardiovascular mortality at baseline year. [ABSTRACT FROM AUTHOR]

Recently, changes in urinary albumin and in GFR have been recognized as risk factors for the development of end-stage kidney disease and mortality. Though most clinical epidemiology studies of chronic kidney disease (CKD) used renal function and proteinuria at baseline alone, definitive diagnosis of CKD with multiple measurements intensifies the differences in the risk for mortality between the CKD and non-CKD populations. We hypothesized that a transient diagnosis of proteinuria and reduced renal function each indicate a significantly higher mortality compared to definitive non-CKD as the negative control and lower mortality compared with definitive CKD as the positive control. The present longitudinal study evaluated a general-population cohort of 338,094 persons who received annual health checkups, with a median 4.3-year study period. There were 2,481 deaths, including 510 CVD deaths (20.6%) and 1,328 cancer deaths (53.5%), and mortality risk was evaluated for transient proteinuria and for transiently reduced renal function. The hazard ratios (HRs) for all-cause mortality and cancer mortality were not significant, but that for cardiovascular mortality was significantly higher for transient proteinuria (HR, 1.94 [95% confidence interval, 1.27–2.96] in men and 2.78 [1.50–5.16] in women). On the other hand, transiently reduced renal function was not significant for either cardiovascular mortality risk or cancer mortality risk. We surmise that this is the first study of the mortality risk of transient dipstick proteinuria in a large general-population cohort with cause-specific death registration. Transiently positive proteinuria appears to be a significant risk specifically for cardiovascular mortality compared with definitely negative for proteinuria. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of the EUVAS-proposed histopathological classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis has been evaluated throughout the world. Here, we performed a Japanese nationwide biopsy survey to assess the association between this histopathological classification and renal prognosis after 2-year follow-up in ANCA-associated glomerulonephritis.Methods: We collected 67 renal biopsy materials of the 321 entries in the RemIT-JAV-RPGN cohort study, and assessed their histologies. Based on the EUVAS-proposed histopathological classification and some histological parameters, we statistically evaluated renal survival and the comparison of renal function for 2 years.Results: Based on the histopathological classification, the largest number of biopsy samples belonged to the Focal class, followed by the Mixed, Crescentic, and Sclerotic classes (n = 30, 19, 10, 8, respectively). Although the number of events might be too low (four patients with renal death) to make this conclusion, the Focal and Mixed classes had higher renal-survival rates compared to the others in the renal-survival curve. Comparing renal function among all classes, the estimated glomerular filtration rate (eGFR) throughout 2-year follow-up period was significantly higher in the Focal class compared to the other 3 classes. The eGFR-values in the Crescentic, Mixed, and Sclerotic classes increased with time. Based on both combined results, the Focal class could be the best prognosis.Conclusion: This histopathological classification was valuable for both the stratification of renal function and the estimation of partial renal survival during 2-year follow-up in ANCA-associated glomerulonephritis. [ABSTRACT FROM AUTHOR]

Accumulation of amyloid fibrils from β2-microglobulin (β2M) was first recognized as a characteristic osteoarticular complication in long-term hemodialysis (HD) patients and called "HD-related amyloidosis" (HRA). However, this syndrome can also be observed in end-stage renal diseases (ESRD) patients undergoing peritoneal dialysis, and even in patients with chronic renal failure before the initiation of dialytic therapy, suggesting that HD is not a direct cause but that accumulation of β2M or some β2M-associated molecules in the body is a common pathogenesis. Currently the term "dialysis-related amyloidosis" (DRA) is widely used for β2M-amyloid (Aβ2M) amyloidosis associated with ESRD, although DRA patients consist mostly of those undergoing long-term HD. Factors other than β2M accumulation also play a role in the formation/local deposition of Aβ2M and disruption of tissue architecture. Conformational changes of β2M by misfolding/unfolding, and promoting/inhibitory effects induced by other coexisting molecules, advanced glycation and oxidation, and direct cell toxicity have also been documented. Two technological improvements of HD have been the keys to prevent the development and progression of DRA: the efficient removal of β2M by using high-flux membranes, high-volume convection and adsorptive column/membrane, as well as the use of biocompatible membranes and dialysates (eg, ultrapure and acetate-free dialysates) have minimized both inflammation and β2M production. Epidemiologically, a decrease in the incidence of DRA has recently been reported; however, longer survival of HD patients may contribute to the development of more DRA, though with a delayed onset. In this article, we describe the pathogenesis of DRA, the strategies developed for its prevention and minimization, and the favorable epidemiological data achieved by these efforts. [ABSTRACT FROM AUTHOR]

Objectives: Owing to recent changes in our understanding of the underlying cause of chronic kidney disease (CKD), the importance of lifestyle modification for preventing the progression of kidney dysfunction and complications has become obvious. In addition, effective cooperation between general physicians (GPs) and nephrologists is essential to ensure a better care system for CKD treatment. In this cluster-randomized study, we studied the effect of behavior modification on the outcome of early- to moderate-stage CKD. Design: Stratified open cluster-randomized trial. Setting: A total of 489 GPs belonging to 49 local medical associations (clusters) in Japan. Participants: A total of 2,379 patients (1,195 in group A (standard intervention) and 1,184 in group B (advanced intervention)) aged between 40 and 74 years, who had CKD and were under consultation with GPs. Intervention: All patients were managed in accordance with the current CKD guidelines. The group B clusters received three additional interventions: patients received both educational intervention for lifestyle modification and a CKD status letter, attempting to prevent their withdrawal from treatment, and the group B GPs received data sheets to facilitate reducing the gap between target and practice. Main outcome measure: The primary outcome measures were 1) the non-adherence rate of accepting continuous medical follow-up of the patients, 2) the collaboration rate between GPs and nephrologists, and 3) the progression of CKD. Results: The rate of discontinuous clinical visits was significantly lower in group B (16.2% in group A vs. 11.5% in group B, p = 0.01). Significantly higher referral and co-treatment rates were observed in group B (p<0.01). The average eGFR deterioration rate tended to be lower in group B (group A: 2.6±5.8 ml/min/1.73 m2/year, group B: 2.4±5.1 ml/min/1.73 m2/year, p = 0.07). A significant difference in eGFR deterioration rate was observed in subjects with Stage 3 CKD (group A: 2.4±5.9 ml/min/1.73 m2/year, group B: 1.9±4.4 ml/min/1.73 m2/year, p = 0.03). Conclusion: Our care system achieved behavior modification of CKD patients, namely, significantly lower discontinuous clinical visits, and behavior modification of both GPs and nephrologists, namely significantly higher referral and co-treatment rates, resulting in the retardation of CKD progression, especially in patients with proteinuric Stage 3 CKD. Trial registration: The University Hospital Medical Information Network clinical trials registry [ABSTRACT FROM AUTHOR]

The prevalence and incidence of end-stage kidney disease (ESKD) have continued to increase worldwide. Japan was known as having the highest prevalence of ESKD in the world; however, Taiwan took this place in 2001, with the USA still in third position. However, the prevalence data from Japan and Taiwan consisted of dialysis patients only. The prevalence and incidence of Kidney Transplantation (KT) in Japan were quite low, and the number of KT patients among those with ESKD was regarded as negligibly small. However, the number of KT recipients has increased recently. Furthermore, there are no reports about nationwide surveys on the prevalence and incidence of predialysis chronic kidney failure patients in Japan. This review describes our recent study on the estimated number of chronic kidney disease (CKD) stage G5 patients and the number of ESKD patients living in Japan, obtained via the cooperation of five related medical societies. From the results, as of Dec 31, 2007, 275,242 patients had received dialysis therapy and 10,013 patients had a functional transplanted kidney, and as of Dec 31, 2008, 286,406 patients had received dialysis therapy and 11,157 patients had a functional transplanted kidney. Consequently, there were 285,255 patients with CKD who reached ESKD and were living in Japan in 2008 and 297,563 in 2009. We also estimated that there were 67,000 predialysis CKD stage G5 patients in 2009, 37,365 patients introduced to dialysis therapy, and 101 patients who received pre-emptive renal transplantation in this year. In total, there were 37,466 patients who newly required renal replacement therapy (RRT) in 2009. Not only the average ages, but also the primary renal diseases of the new ESKD patients in each RRT modality were different. [ABSTRACT FROM AUTHOR]

Background: Our recently published cost-effectiveness study on chronic kidney disease mass screening test in Japan evaluated the use of dipstick test, serum creatinine (Cr) assay or both in specific health checkup (SHC). Mandating the use of serum Cr assay additionally, or the continuation of current policy mandating dipstick test only was found cost-effective. This study aims to examine the affordability of previously suggested reforms. Methods: Budget impact analysis was conducted assuming the economic model would be good for 15 years and applying a population projection. Costs expended by social insurers without discounting were counted as budgets. Results: Annual budget impacts of mass screening compared with do-nothing scenario were calculated as ¥79-¥−1,067 million for dipstick test only, ¥2,505-¥9,235 million for serum Cr assay only and ¥2,517-¥9,251 million for the use of both during a 15-year period. Annual budget impacts associated with the reforms were calculated as ¥975-¥4,129 million for mandating serum Cr assay in addition to the currently used mandatory dipstick test, and ¥963-¥4,113 million for mandating serum Cr assay only and abandoning dipstick test. Conclusions: Estimated values associated with the reform from ¥963-¥4,129 million per year over 15 years are considerable amounts of money under limited resources. The most impressive finding of this study is the decreasing additional expenditures in dipstick test only scenario. This suggests that current policy which mandates dipstick test only would contain medical care expenditure. [ABSTRACT FROM AUTHOR]

Aims Chronic kidney disease is a risk factor of the development of cardiovascular disease ( CVD). However, it is not clear whether decline of glomerular filtration rate ( GFR), not reduced GFR, is a risk factor for the incidence of CVD independent of proteinuria. Methods By using a population-based 521 123 person-years longitudinal cohort receiving annual health checkups from 2008 to 2010, we examined whether the annual decline of estimated GFR is a risk factor for CVD development independent of proteinuria. Results During the follow-up period, there were 12 041 newly developed CVD events, comprising 4426 stroke events and/or 8298 cardiac events. As expected, both reduced estimated GFR and proteinuria were risk factors for the development of CVD in our study population. Moreover, annual decline of estimated GFR was a significant and independent risk factor for the incidence of CVD ( HR [95% CI], 1.23 [1.18-1.28] in males or 1.14 [1.10-1.18] in females for −10% per year) with covariant adjustment for proteinuria and reduced estimated GFR. Conclusion Annual decline of GFR is an independent risk factor for CVD. Serial measurement of both creatinine and proteinuria would be better to predict the incidence of CVD in the general population. [ABSTRACT FROM AUTHOR]

Renal involvement with significant organ damage is common in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). As a result, it is independently referred to ANCA-associated renal vasculitis. Clinically, ANCA-associated renal vasculitis is characterized by rapidly progressive glomerulonephritis. Pathologically, it is defined by pauci-immune type necrotizing and crescentic glomerulonephritis. According to previous reports from all over the world, the etiology, prevalence, and prognosis of RPGN including ANCA-associated renal vasculitis varies among races and periods. To elucidate the clinical characteristics of Japanese RPGN patients, a registry derived from a questionnaire survey was established in 1999 and maintained until 2006. As a result, 1,772 cases were collected, analyzed, and reported previously. In this mini-review, we outline the characteristic clinical findings of Japanese patients (Asian) with ANCA-associated renal vasculitis, based on the registry data. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to standardize treatment and determine patient and renal outcome in Japanese anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis/rapidly progressive glomerulonephritis (AAV/RPGN) patients, because the prognosis of AAV/RPGN patients in Japan had been poor compared with that of other countries. Methods: The participants in this retrospective cohort study were 824 ANCA-positive RPGN patients, 705 of whom were only myeloperoxidase (MPO)-ANCA positive. Results: Among the early-years cohort (group A; cases diagnosed between 1988 and 1998), patients frequently died due to opportunistic infection. Therefore, we recommended a reduced dose of prednisolone (oral prednisolone dose <0.8 mg/kg/day) with or without cyclophosphamide for initial treatment of Japanese RPGN patients. After this recommendation, 1-year survival of the patients improved: 75% in group A, 79% in group B (between 1999 and 2002), and 81% in group C (after 2003). During the entire observation period, average serum creatinine level at the start of treatment decreased, and improvement of 1-year renal survival was also found (72% in group A, 83% in group B, and 83% in group C), while the recurrence rate was significantly increased in group C (0.05/patient-year in group A, 0.07/patient-year in group B, and 0.13/patient-year in group C). Conclusions: Oral prednisolone dose <0.8 mg/kg/day with or without cyclophosphamide as an initial treatment could improve patient survival in older Japanese AAV/RPGN patients. However, maintenance treatment avoiding relapse should be established to improve renal outcomes. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a significant public health problem. Strategy for its early detection is still controversial. This study aims to assess the cost-effectiveness of population strategy, i.e. mass screening, and Japan's health checkup reform. Methods: Cost-effectiveness analysis was carried out to compare test modalities in the context of reforming Japan's mandatory annual health checkup for adults. A decision tree and Markov model with societal perspective were constructed to compare dipstick test to check proteinuria only, serum creatinine (Cr) assay only, or both. Results: Incremental cost-effectiveness ratios (ICERs) of mass screening compared with do-nothing were calculated as ¥1,139,399/QALY (US $12,660/QALY) for dipstick test only, ¥8,122,492/QALY (US $90,250/QALY) for serum Cr assay only and ¥8,235,431/QALY (US $91,505/QALY) for both. ICERs associated with the reform were calculated as ¥9,325,663/QALY (US $103,618/QALY) for mandating serum Cr assay in addition to the currently used mandatory dipstick test, and ¥9,001,414/QALY (US $100,016/QALY) for mandating serum Cr assay and applying dipstick test at discretion. Conclusions: Taking a threshold to judge cost-effectiveness according to World Health Organization's recommendation, i.e. three times gross domestic product per capita of ¥11.5 million/QALY (US $128 thousand/QALY), a policy that mandates serum Cr assay is cost-effective. The choice of continuing the current policy which mandates dipstick test only is also cost-effective. Our results suggest that a population strategy for CKD detection such as mass screening using dipstick test and/or serum Cr assay can be justified as an efficient use of health care resources in a population with high prevalence of the disease such as in Japan and Asian countries. [ABSTRACT FROM AUTHOR]

The continuous increase in the number of people requiring dialysis is a major clinical and socioeconomical issue in Japan and other countries. This study was designed to encourage chronic kidney disease (CKD) patients to consult a physician, enhance cooperation between nephrologists and general practices, and prevent the progression of kidney disease. Subjects comprise CKD patients aged between 40 and 74 years consulting a general physician, and patients in CKD stage 3 with proteinuria and diabetes or hypertension. This trial is a stratified open cluster-randomized study with two intervention groups: group A (weak intervention) and group B (strong intervention). We have recruited 49 local medical associations (clusters) in 15 different prefectures, which were classified into four regions (strata) based on the level of increase rate of dialysis patients. The patients in group A clusters were instructed initially to undergo treatment in accordance with the current CKD treatment guide, whereas patients in group B clusters were not only instructed in the same fashion but also received support from an information technology (IT)-based system designed to help achieve the goals of CKD treatment, consultation support centers, and consultations by dietitians visiting the local general practice offices. We assessed the rates of continued consultation, collaboration between general practitioners and nephrologists, and progression of CKD (as expressed by CKD stage). Through this study, filling the evidence-practice gap by facilitating effective communication and supporting general physicians and nephrologists, we will establish a CKD care system and decrease the number of advanced-stage CKD patients. [ABSTRACT FROM AUTHOR]

The etiology, prevalence, and prognosis of rapidly progressive glomerulonephritis (RPGN) including renal vasculitis vary among races and periods. To improve the prognosis of Japanese RPGN patients, we conducted a nationwide survey of RPGN in the nephrology departments of 351 tertiary hospitals, and found 1772 patients with RPGN (Group A: diagnosed between 1989 and 1998, 884 cases; Group B: diagnosed between 1999 and 2001, 321 cases; and Group C: diagnosed between 2002 and 2007, 567 cases). ANCA subclasses, renal biopsy findings, treatment, outcome and cause of death were recorded. The most frequent primary disease was renal-limited vasculitis (RLV) (42.1%); the second was microscopic polyangiitis (MPA) (19.4%); the third was anti-GBM-associated RPGN (6.1%). MPO-ANCA was positive in 88.1% of RLV patients and 91.8% of MPA patients. The proportion of primary renal diseases of RPGN was constant during those periods. The most frequent cause of death was infectious complications. The serum creatinine at presentation and the initial dose of oral prednisolone decreased significantly in Groups B and C compared to Group A. However, both patient and renal survival rates improved significantly in Groups B and C (survival rate after six months in Group A: 79.2%, Group B: 80.1%, and Group C: 86.1%. Six-month renal survival in Group A: 73.3%, Group B: 81.3%, and Group C: 81.8%). Early diagnosis was the most important factor for improving the prognosis of RPGN patients. To avoid early death due to opportunistic infection in older patients, a milder immunosuppressive treatment such as an initial oral prednisolone dose reduction with or without immunosuppressant is recommended. [ABSTRACT FROM AUTHOR]

Anti-glomerular basement membrane (anti-GBM) antibody disease is a rare, but well characterized cause of glomerulonephritis. It is defined by the presence of autoantibodies directed at specific antigenic targets within the glomerular basement membrane. This pattern of rapidly progressive glomerulonephritis and alveolar hemorrhage is often referred to as Goodpasture’s syndrome. The prognosis for patients with anti-GBM antibody disease is poor. In Japan, to improve the prognosis of patients with rapidly progressive glomerulonephritis (RPGN), we conducted a nationwide survey of patients with RPGN and investigated the initial symptoms, laboratory findings including renal biopsy findings, treatment methods, and outcomes. Among patients with RPGN, patients with anti-GBM antibody disease were rare: 6.6% (47/715). Alveolar hemorrhage (Goodpasture’s syndrome) was observed in 23.4% of patients with anti-GBM antibody disease. Most patients with anti-GBM antibody disease had renal failure at the time of diagnosis. The mean serum creatinine level of patients with renal-limited anti-GBM antibody disease was 7.07 ± 4.21 mg/dl and that of patients with Goodpasture’s syndrome was 7.99 ± 4.31 mg/dl. The mean level of crescent formation was 78.99 ± 23.54% in patients with anti-GBM antibody disease, and a cellular crescent form was observed in 63.2% of those patients. The prognosis for patients with anti-GBM antibody disease is poor; the renal survival rate at 6 months after onset was 20.9%, and the mortality at 6 months after onset was 23.3%. To improve the prognosis for anti-GBM antibody disease, it may be necessary to detect this disease in the early stages and to treat it without delay. [ABSTRACT FROM AUTHOR]

There are racial differences in primary renal diseases for end-stage renal disease (ESRD) and the incidence and prevalence of cardiovascular disease (CVD). To reduce the number of patients with both ESRD and CVD, an effective screening method for CKD should be established. In Japan, screening with the urine dip-stick test for proteinuria has been used since 1972 targeting every child and worker and since 1983 for every resident over 40 years old. There are several reasons for continuing this screening program. First, the positive rate of proteinuria is high in the Japanese general population, especially subjects with neither hypertension nor diabetes. Most of these subjects have no symptoms, and the only sign of renal disease is asymptomatic urinary abnormalities. Second, the prevalence and incidence of glomerulonephritis, especially IgA nephropathy, are high in the Japanese and Asian races, and urinalysis is the only method for early detection of chronic glomerulonephritis. Third, 10-year survival of the ESRD patients due to glomerulonephritis was approximately twice that of ESRD patients due to diabetes and nephrosclerosis. Consequently, reducing the incidence of ESRD due to glomerulonephritis is one of the best ways to reduce the prevalence of ESRD. Furthermore, higher incidence of ESRD in Asian races than in Caucasians was reported. Proteinuria is known to be the best predictor for reducing renal function, and the urine dip-stick test for proteinuria is less expensive and is cost-effective. For an effective screening strategy to reduce the ESRD population in Japanese and Asians, universal screening with the urine dip-stick test for proteinuria could be one solution. [ABSTRACT FROM AUTHOR]

In the Original publication of the article, the text in the horizontal axis in Fig. 1a and b appears incorrectly as "Time from treatment start (Months)". [ABSTRACT FROM AUTHOR]

Anemia and chronic kidney disease (CKD), which worsen bidirectionally, are associated with mortality in older adults. This study aimed to examine the association between CKD and the type of anemia and its impact on mortality in the general population. Data from a nationwide database of 203,280 individuals who participated in the annual "Specific Health Check and Guidance in Japan" evaluation between 2008 and 2011 were used. Over a follow-up period of 4 years, 2,819 all-cause, 1,595 cancer-related, 523 cardiovascular, and 128 infectious disease deaths were recorded. Macrocytic anemia was detected in 2.3% of participants. The prevalence of normocytic and macrocytic anemia increased with advancing CKD stage. Multivariate Cox proportional hazards regression analysis revealed significant associations between macrocytic anemia and the all-cause, cancer, and cardiovascular mortality rates. Including the anemia type improved the prediction accuracy for all-cause deaths. The participants were divided into eight groups based on the anemia type and CKD. Macrocytic anemia of CKD had the highest hazard ratio for all-cause mortality in the general population. A correlation was observed between macrocytic anemia and CKD. Macrocytic anemia predicted mortality in the general population, suggesting that it could serve as an early indicator of premature death in high-risk individuals. [ABSTRACT FROM AUTHOR]

The billing database of the universal healthcare system in Japan potentially includes large-cohort data of patients with immunoglobulin A nephropathy, diagnosis codes aimed at billing should not be directly used for clinical research because of the risk of misdiagnosis. To solve this problem, we aimed to develop a novel method for identifying patients with immunoglobulin A nephropathy from billing data using machine learning. The medical records and bills of 3,743 patients who consulted nephrologists at a single center were extracted. Patients were labeled to have been diagnosed with immunoglobulin A nephropathy through a review of medical records. A manual analysis of the diagnostic accuracy and machine learning was performed. For machine learning, the datasets were preprocessed in three patterns and assigned to the XGBoost program using five-fold cross-validation. Of all the participants, 437 were labeled as having been diagnosed with immunoglobulin A nephropathy. Bill codes for immunoglobulin A nephropathy were provided to approximately half of them. The manually created criteria consisting of the recommended examinations and treatments in the Japanese guidelines for immunoglobulin A nephropathy showed both specificity and sensitivity < 0.8. In contrast, with the receiver operating characteristic curve analysis, the machine learning process yielded area under the curve values over 0.9 with preprocessing from the clinical viewpoint. Applying machine learning technology to a dataset preprocessed from a clinical viewpoint achieved a high performance in detecting patients with immunoglobulin A nephropathy. This methodology contributes to the construction of a disease-specific cohort using big bill data. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Obesity indices reflect not only fat mass but also muscle mass and nutritional status in older people. Therefore, they may not accurately reflect prognosis. This study aimed to investigate associations between a body shape index (ABSI), body mass index (BMI), and mortality in the general older population.This nationwide observational longitudinal study included individuals aged between 65 and 74 years who underwent annual health checkups between 2008 and 2014. Exposures of interest were ABSI and BMI, and the primary outcome was all‐cause mortality. Association between the ABSI and BMI quartile (Q1–4) and mortality was assessed using Cox regression analysis. A restricted cubic spline was also used to investigate nonlinear associations. The missing values were imputed using multiple imputation by chained equations.Among 315,215 participants, 5074 died during a median follow‐up period of 42.5 (interquartile range: 26.2–59.3) months. Compared with ABSI Q1, ABSI Q3 and Q4 were associated with increased risk of mortality, with the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 1.13 (1.05–1.22) and 1.23 (1.13–1.35), respectively. Compared with BMI Q3, BMI Q1 and Q2 were associated with an increased risk of mortality, with aHRs and 95% CIs of 1.51 (1.39–1.65) and 1.12 (1.03–1.22), respectively. The impacts of these indices were greater in male than in female. The heatmap of the aHR for mortality by continuous ABSI and BMI showed that higher ABSI was consistently associated with higher mortality risk regardless of BMI, and that the combination of low BMI and high ABSI was strongly associated with increased mortality risk.High ABSI and low BMI are additively associated with the risk of all‐cause mortality in the general older population in Japan. Combination of ABSI and BMI is useful for evaluating mortality risk in older people. [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]

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]

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]

Background: In Japan, the Specific Health Check and Guidance (Tokutei-Kenshin) has started in 2008. However, the relationship between the baseline characteristics and mortality has not been examined. Methods: Subjects were those who participated at the 2008 Tokutei-Kenshin in six districts with baseline data of serum creatinine. Using National database of death certificate from 2008 to 2012, we identified those who might have died and confirmed further with the collaborations of the regional National Health Insurance agency and public health nurses. The data was released to the research team supported by the Ministry of Health, Labor, and Welfare of Japan, and is governed by strict regulation and is completely encrypted with the individual's name and residence. Causes of death were classified by ICD-10. Results: Among the total of 295,297 subjects, we identified 3764 fatal cases by end of 2012. The median BMI was 23.8 kg/m in men and 22.5 kg/m in women, respectively. Proteinuria, dipstick 1+ and over, was positive in 5.3%. The median eGFR was 73.8 ml/min/1.73 m among those with data available in 81% of the total cohort ( N = 239,274). The leading cause of death was neoplasm in both genders. It was 51.6% of the total, 50.4% in men and 53.7% in women. The second cause of death was circulatory; 20.4% of the total, 21.1% in men and 19.2% in women. Conclusion: Half of the causes of death was related to neoplasm among the cohort of the Tokutei-Kenshin. Effects of baseline demographics such as lifestyle and CKD remained to be studied. [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]

Background: Although several studies have examined the Kidney Disease Quality of Life (KDQOL) in patients with chronic kidney disease (CKD), the factors associated with kidney-related symptoms have not been fully explored.This nationwide multicenter cohort study enrolled 2248 patients. To identify the factors associated with each item or the three KDQOL domains, such as burden of kidney disease, symptoms/problems of kidney disease, and impact of kidney disease on daily life, multiple regression analysis was performed using baseline data.The study population had a mean age of 69.1 ± 12.6 years, comprised 64.7% men, and had mean estimated glomerular filtration rate (eGFR) of 23.2 ± 10.4 mL/min/1.73 m2. Mean serum creatinine levels were 1.4 ± 0.2, 2.3 ± 0.5, and 4.5 ± 1.5 mg/dL for G3b, G4, and G5, respectively. The mean scores in the three KDQOL domains among CKD stages showed significantly decreasing trends. Of all the 11 symptoms assessed, 6 had scores that significantly decreased as the CKD stage progressed and 9 had scores that significantly decreased as the age category group increased. Multiple regression analysis revealed eGFR as a significantly associated factor for 5 of 11 symptoms. Age, body mass index, and comorbidities were also detected as significant factors for some symptoms.In addition to eGFR, several factors were associated with symptoms in patients with CKD. Nephrologists need to recognize renal dysfunction-specific symptoms and explore other plausible causes of nonspecific symptoms.Methods: Although several studies have examined the Kidney Disease Quality of Life (KDQOL) in patients with chronic kidney disease (CKD), the factors associated with kidney-related symptoms have not been fully explored.This nationwide multicenter cohort study enrolled 2248 patients. To identify the factors associated with each item or the three KDQOL domains, such as burden of kidney disease, symptoms/problems of kidney disease, and impact of kidney disease on daily life, multiple regression analysis was performed using baseline data.The study population had a mean age of 69.1 ± 12.6 years, comprised 64.7% men, and had mean estimated glomerular filtration rate (eGFR) of 23.2 ± 10.4 mL/min/1.73 m2. Mean serum creatinine levels were 1.4 ± 0.2, 2.3 ± 0.5, and 4.5 ± 1.5 mg/dL for G3b, G4, and G5, respectively. The mean scores in the three KDQOL domains among CKD stages showed significantly decreasing trends. Of all the 11 symptoms assessed, 6 had scores that significantly decreased as the CKD stage progressed and 9 had scores that significantly decreased as the age category group increased. Multiple regression analysis revealed eGFR as a significantly associated factor for 5 of 11 symptoms. Age, body mass index, and comorbidities were also detected as significant factors for some symptoms.In addition to eGFR, several factors were associated with symptoms in patients with CKD. Nephrologists need to recognize renal dysfunction-specific symptoms and explore other plausible causes of nonspecific symptoms.Results: Although several studies have examined the Kidney Disease Quality of Life (KDQOL) in patients with chronic kidney disease (CKD), the factors associated with kidney-related symptoms have not been fully explored.This nationwide multicenter cohort study enrolled 2248 patients. To identify the factors associated with each item or the three KDQOL domains, such as burden of kidney disease, symptoms/problems of kidney disease, and impact of kidney disease on daily life, multiple regression analysis was performed using baseline data.The study population had a mean age of 69.1 ± 12.6 years, comprised 64.7% men, and had mean estimated glomerular filtration rate (eGFR) of 23.2 ± 10.4 mL/min/1.73 m2. Mean serum creatinine levels were 1.4 ± 0.2, 2.3 ± 0.5, and 4.5 ± 1.5 mg/dL for G3b, G4, and G5, respectively. The mean scores in the three KDQOL domains among CKD stages showed significantly decreasing trends. Of all the 11 symptoms assessed, 6 had scores that significantly decreased as the CKD stage progressed and 9 had scores that significantly decreased as the age category group increased. Multiple regression analysis revealed eGFR as a significantly associated factor for 5 of 11 symptoms. Age, body mass index, and comorbidities were also detected as significant factors for some symptoms.In addition to eGFR, several factors were associated with symptoms in patients with CKD. Nephrologists need to recognize renal dysfunction-specific symptoms and explore other plausible causes of nonspecific symptoms.Conclusions: Although several studies have examined the Kidney Disease Quality of Life (KDQOL) in patients with chronic kidney disease (CKD), the factors associated with kidney-related symptoms have not been fully explored.This nationwide multicenter cohort study enrolled 2248 patients. To identify the factors associated with each item or the three KDQOL domains, such as burden of kidney disease, symptoms/problems of kidney disease, and impact of kidney disease on daily life, multiple regression analysis was performed using baseline data.The study population had a mean age of 69.1 ± 12.6 years, comprised 64.7% men, and had mean estimated glomerular filtration rate (eGFR) of 23.2 ± 10.4 mL/min/1.73 m2. Mean serum creatinine levels were 1.4 ± 0.2, 2.3 ± 0.5, and 4.5 ± 1.5 mg/dL for G3b, G4, and G5, respectively. The mean scores in the three KDQOL domains among CKD stages showed significantly decreasing trends. Of all the 11 symptoms assessed, 6 had scores that significantly decreased as the CKD stage progressed and 9 had scores that significantly decreased as the age category group increased. Multiple regression analysis revealed eGFR as a significantly associated factor for 5 of 11 symptoms. Age, body mass index, and comorbidities were also detected as significant factors for some symptoms.In addition to eGFR, several factors were associated with symptoms in patients with CKD. Nephrologists need to recognize renal dysfunction-specific symptoms and explore other plausible causes of nonspecific symptoms. [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]