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

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

Health-related Quality of Life in 10 years Long-term Survivors of Chronic Kidney Disease: A From-J Study.

OBJECTIVE: The Chronic Kidney Disease (CKD) practice facilitation program in the Frontier of Renal Outcome Modifications in Japan study reduced cardiovascular disease (CVD) events in patients with CKD. 10-year long-term survivors with CKD lived with serious complications, including end-stage kidney disease and CVD. This study aimed to measure health-related quality of life in 10-year long-term CKD survivors and examine the predictors and determinants of clinical indices for measured quality of life (QOL) scores. METHODS: The EQ-5D-5L, a generic preference-based instrument, was administered to 1,473 CKD survivors enrolled in the Frontier of Renal Outcome Modifications in JapanFrontier of Renal Outcome Modifications in JapanFrontier of Renal Outcome Modifications in Japan study. The 10th-year data collection was performed by either primary care physicians or participants who filled out questionnaires from October 2018 to March 31, 2019. RESULTS: The response rate was 38.2% (423/1,473). The mean QOL score was 0.893 (95% confidence interval (CI), 0.880-0.906), and the median QOL score was 1.000 (interquartile range (IQR), 0.826-1.000). The mean QOL score in participants with renal replacement therapy was 0.824 (95% CI, 0.767-0.881), and the median was 0.828 (IQR, 0.755-1.000). The mean QOL score in participants with CVD was 0.877 (95% CI, 0.811-0.943), and the median was 1.000 (IQR, 0.723-1.000). The mean QOL score in participants with 50% decline in estimated glomerular filtration was 0.893 (95% CI, 0.860-0.926), and the median was 0.889 (IQR, 0.825-1.000). The decrease in QOL scores with baseline CKD stages was significant according to the Jonckheere-Terpstra test for trend (P = .002). Baseline age, systolic blood pressure, and history of hyperuricemia were significant predictors of 10th-year QOL scores. CONCLUSION: We suggest that CKD complications negatively affect the QOL scores in 10-year long-term survivors with CKD. CKD guideline-based practices, prevention of end-stage kidney disease/CVD and management of hypertension, diabetes and hyperuricemia, might contribute to future health-related quality of life in patients with CKD.

Blood Pressure, Hypertension, and the Risk of Aortic Dissection Incidence and Mortality: Results From the J-SCH Study, the UK Biobank Study, and a Meta-Analysis of Cohort Studies.

BACKGROUND: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies on this topic have been published. We investigated the association between hypertension/elevated BP and AD in 2 cohorts and conducted a meta-analysis of published prospective studies, including these 2 studies. METHODS: We analyzed data from the J-SHC study (Japan-Specific Health Checkups) and UK Biobank, which prospectively followed up 534 378 and 502 424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios and 95% CIs for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks were calculated with random-effects models. A potential nonlinear dose-response relationship between BP and AD was tested with fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined. RESULTS: In the J-SHC study and UK Biobank, there were 84 and 182 ADs during the 4- and 9-year follow-up, and the adjusted hazard ratios of AD were 3.57 (95% CI, 2.17-6.11) and 2.68 (95% CI, 1.78-4.04) in hypertensive individuals, 1.33 (95% CI, 1.05-1.68) and 1.27 (95% CI, 1.11-1.48) per 20-mm Hg increase in systolic BP (SBP), and 1.67 (95% CI, 1.40-2.00) and 1.66 (95% CI, 1.46-1.89) per 10-mm Hg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary relative risks were 3.07 (95% CI, 2.15-4.38, I2=76.7%, n=7 studies, 2818 ADs, 4 563 501 participants) for hypertension and 1.39 (95% CI, 1.16-1.66, I2=47.7%, n=3) and 1.79 (95% CI: 1.51-2.12, I2 = 57.0%, n=3) per 20-mm Hg increase in SBP and per 10-mm Hg increase in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mm Hg and DBP >75 mm Hg. CONCLUSIONS: Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.

Association of polypharmacy with incidence of CKD: a retrospective cohort study.

BACKGROUND: Polypharmacy is common in patients with chronic kidney disease (CKD) and is associated with a decline in kidney function. However, its impact on patients without CKD has not been adequately elucidated. Therefore, we aimed to investigate the association between polypharmacy and the incidence of CKD. METHODS: We conducted retrospective cohort study using 1221 participants who were enrolled in the Fukushima Cohort Study with one or more risk factors of CKD, an estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m2, and without proteinuria. Participants were categorized into three groups based on the number of medications: non-polypharmacy, 0-4 medications; polypharmacy, 5-9 medications; and hyper-polypharmacy, ≥ 10 medications. RESULTS: The median age was 62 years, 49% were men, the median eGFR was 75.4 ml/min/1.73 m2, and the median number of medications was 5. Polypharmacy and hyper-polypharmacy were noted in 506 (41%) and 250 (20%) participants, respectively. During follow-up, 288 participants developed CKD and 67 cardiovascular events were observed. Compared to the non-polypharmacy group, the hyper-polypharmacy group had a higher risk of CKD and cardiovascular events. The adjusted hazard ratios were 1.41 (95% CI1.01-1.99) and 2.24 (95% CI1.05-4.78) for the incidence of CKD and cardiovascular events, respectively. Sensitivity analyses yielded similar findings for the restricted cubic spline function models. CONCLUSIONS: Hyper-polypharmacy is associated with a higher risk of CKD and cardiovascular events.

Hematological parameters of anemia and prognosis of non-dialysis-dependent chronic kidney disease: the Fukushima CKD cohort study.

BACKGROUND: Mean corpuscular volume (MCV) and red cell distribution width (RDW), as well hemoglobin, are reported to be associated with mortality in various populations. However, associations between such hematological parameters and adverse outcomes in patients with CKD have not been sufficiently elucidated. METHODS: A total of 1,320 participants enrolled in the Fukushima CKD Cohort Study were examined to investigate associations between hematological parameters of anemia (MCV and RDW) and adverse outcomes, such as ESKD, all-cause death, and cardiovascular events, in patients with non-dialysis-dependent CKD. Baseline hematological parameters were grouped as follows: hemoglobin into 3 categories (< 11.0 g/dL, 11.0 ≤ - < 13.0 g/dL [reference], and ≥ 13.0 g/dL); MCV into 5 categories (< 90 fL, ≥ 90 - < 94 fL [reference], ≥ 94 - < 98 fL, ≥ 98 - < 102 fL, and ≥ 102 fL); and RDW into 2 categories (< 13.6% [reference] vs ≥ 13.6%). RESULTS: During the median observational period of 4.7 years, 120 patients developed ESKD, 160 developed cardiovascular events, and 122 died. Hemoglobin < 11 g/dL (hazard ratio [HR] 1.56, 95% confidence interval [CI], 1.00-2.42), MCV < 90 fL (HR 2.01, 95% CI 1.14-3.54), and RDW ≥ 13.6% (HR 1.57, 95% CI 1.01-2.42) were significantly associated with higher risks of ESKD. Hemoglobin < 11 g/dL, MCV ≥ 98 fL, and RDW ≥ 13.6% were significantly associated with higher risks of all-cause death. No significant associations between hematological parameters and risk of cardiovascular events were confirmed. CONCLUSION: In patients with non-dialysis-dependent CKD, MCV, RDW, and hemoglobin were associated with increased risks of ESKD and all-cause mortality.

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

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

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

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

Bisphosphonate treatment is associated with decreased mortality rates in patients after osteoporotic vertebral fracture.

The aim of this study is to investigate the effect of bisphosphonate (BP) on mortality after osteoporotic vertebral fracture (OVF). BP medication (hazard ratios = 0.593; 95%CI: 0.361-0.976) was significantly associated with reduced all-cause mortality after OVF. PURPOSE: Osteoporotic vertebral fracture (OVF) is the most common type of fragility fracture. Bisphosphonate (BP) medication was suggested to have positive effects on both fracture prevention and recovery outcomes. The aim of this study is to investigate the effect of BP on mortality after OVF. METHODS: This cohort study involved 535 patients (170 males and 365 females), aged ≥ 65 years (mean age: 82.6 ± 7.0 years, mean follow-up periods: 33.0 ± 25.8 months) who were hospitalized after OVF from January 2011 to December 2019 at a public hospital. Patients treated with PTH (parathyroid hormone), PTH or PTHrp analogues, denosumab, and selective estrogen receptor modulators were excluded. Kaplan-Meier survival curves on mortality of patients with OVF with and without BP treatment were prepared, and log-rank tests were performed. Cox proportional hazards model was used to identify factors associated with mortality after OVF. RESULTS: This study included 163 (30.5%) patients treated with BP. Kaplan-Meier survival curves showed that the mortality rate after OVF was significantly lower in patients treated with BP (P < 0.001). Cox proportional hazards model showed that older age (hazard ratios [HR] = 1.066; 95%CI:1.035-1.103), male sex (HR = 2.248; 95%CI:1.427-3.542), malnutrition (geriatric nutritional risk index < 92) (HR = 1.691; 95%CI:1.005-2.846), BP medication (HR = 0.593; 95%CI: 0.361-0.976), and Japanese Orthopaedic Association score at discharge (HR = 0.941; 95%CI: 0.892-0.993) were significantly associated with all-cause mortality after OVF. CONCLUSIONS: BP medication is beneficial not only for fracture prevention but also for mortality after OVF.

A Comparative Study of Serum Phosphate and Related Parameters in Chronic Kidney Disease between the USA and Japan.

INTRODUCTION: Recent studies have suggested a higher incidence of cardiovascular disease (CVD) among patients with chronic kidney disease (CKD) in the USA than in Japan. Hyperphosphatemia, a possible risk for CVD, may explain this difference; however, international differences in phosphate parameters in CKD have not been well elaborated. METHODS: By using the baseline data from the USA and the Japanese nation-wide, multicenter, CKD cohort studies; the Chronic Renal Insufficiency Cohort Study (CRIC, N = 3,870) and the Chronic Kidney Disease-Japan Cohort Study (CKD-JAC, N = 2,632), we harmonized the measures and compared clinical parameters regarding phosphate metabolism or serum phosphate, fibroblast growth factor-23 (FGF23), and parathyroid hormone (PTH), in the cross-sectional model. RESULTS: Multivariable linear regression analyses revealed that serum phosphate levels were significantly higher in CRIC across all levels of estimated glomerular filtration rate (eGFR) with the greatest difference being observed at lower levels of eGFR. Serum FGF23 and 25-hydroxy vitamin D (25OHD) levels were higher in CRIC, while PTH levels were higher in CKD-JAC at all levels of eGFR. Adjustments for demographics, 25OHD, medications, dietary intake or urinary excretion of phosphate, PTH, and FGF23 did not eliminate the difference in serum phosphate levels between the cohorts (0.43, 0.46, 0.54, 0.64, and 0.78 mg/dL higher in CRIC within eGFR strata of >50, 41-50, 31-40, 21-30, and ≤20 mL/min/1.73 m2, respectively). These findings were consistent when only Asian CRIC participants (N = 105) were included in the analysis. CONCLUSION: Serum phosphate levels in CRIC were significantly higher than those of CKD-JAC across all stages of CKD, which may shed light on the international variations in phosphate parameters and thus in cardiovascular risk among CKD patients. The key mechanisms for the substantial differences in phosphate parameters need to be elucidated.

Behaviour modification intervention for patients with chronic kidney disease could provide a mid- to long-term reduction in public health care expenditure: budget impact analysis.

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.

Elevated red blood cell distribution width is associated with poor outcome in osteoporotic vertebral fracture.

INTRODUCTION: Red blood cell distribution width (RDW) has been evaluated as a potential screening marker for cancer and prognostic marker in heart failure and coronary heart disease. Recent studies have been suggested the association of RDW with mortality in patients with hip fracture and arthroplasty. Objective of this study was to investigate whether RDW as a prognostic marker is significant in patients with osteoporotic vertebral fracture (OVF). MATERIALS AND METHODS: Total of 460 patients with fresh OVF from January 2014 and September 2017 were assessed for a 1-year follow-up period. The cutoff value for RDW was set at 15%, and outcomes of conservative treatment of OVF were evaluated using the Japanese Orthopaedic Association (JOA) scores, Barthel index, and walking state. RESULTS: Of the total 460 patients, 125 patients (27.2%) had an elevated RDW. RDW value was not correlated with osteoporotic parameters. Both JOA score and Barthel index were significantly lower at 1 year after treatment in the elevated RDW group. In the elevated RDW group, 21 patients died within 1 year (mortality 16.8%) compared with 7 patients (mortality 2.1%) in the non-elevated RDW group; this was statistically significant. Multivariate statistical analysis showed elevated RDW, independent walk before OVF and skeletal muscle mass index (SMI) remained independent factors associated with abasia after OVF affected. CONCLUSION: Elevated RDW was associated with the poor clinical outcomes of conservative treatment of an OVF, independent of osteoporosis or severity of the OVF. RDW provides prognostic information for risk stratification as a senescence biomarker.

One-Year Change in Diastolic Blood Pressure and Aortic Disease-Related Mortality in a Japanese General Population Aged 50-75 Years.

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

Application of MALDI-TOF MS to assess clinical characteristics, risk factors, and outcomes associated with anaerobic bloodstream infection: a retrospective observational study.

BACKGROUND: Correctly identifying anaerobic bloodstream infections (BSIs) is difficult. However, a new technique, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), enables more accurate identification and appropriate treatment. Anaerobic BSIs identified by MALDI-TOF MS were retrospectively analyzed to determine the clinical and microbiological features and patient outcomes based on the anaerobic genera or group. METHODS: Medical records of patients with anaerobic BSIs were used to conduct a single-center retrospective cohort study from January 2016 to December 2020 in Nagoya, Japan. Multivariate logistic regression analysis was performed to determine the independent risk factors for in-hospital mortality. RESULTS: Of the 215 patients with anaerobic BSIs, 31 had multiple anaerobic organisms in the blood culture, including 264 total episodes of anaerobic BSIs. Bacteroides spp. were isolated the most (n = 74), followed by gram-positive non-spore-forming bacilli (n = 57), Clostridium spp. (n = 52), gram-positive anaerobic cocci (GPAC) (n = 27), and gram-negative cocci (n = 7). The median patient age was 76 years; 56.7% were male. The most common focal infection site was intra-abdominal (36.7%). The in-hospital mortality caused by anaerobic BSIs was 21.3%, and was highest with Clostridium spp. (36.5%) and lowest with GPAC (3.7%). Age, solid tumors, and Clostridium spp. were independent risk factors for in-hospital mortality. CONCLUSIONS: We identified current anaerobic BSI trends using MALDI-TOF MS and reported that mortality in patients with anaerobic BSIs patients was highest with Clostridium spp. infections.

Association between serum potassium levels and adverse outcomes in chronic kidney disease: the Fukushima CKD cohort study.

BACKGROUND: Serum potassium disorders, commonly observed in chronic kidney disease (CKD), are reportedly associated with higher mortality, but their impact on renal outcomes is still controversial. METHODS: The present study used the longitudinal data of the Fukushima CKD cohort study to investigate the relationships between hypokalemia and hyperkalemia and adverse outcomes such as renal outcomes and all-cause mortality in Japanese patients with non-dialysis-dependent CKD. The study involved 1330 CKD patients followed-up for 2.8 years. The primary endpoint of the present study was a kidney event, defined as a combination of doubling of baseline serum creatinine and end-stage kidney disease. RESULTS: Hyperkalemia (≥ 5.0 mmol/L) was noted in 10.6% and hypokalemia (< 4.0 mmol/L) in 16.4% of the study population. Significant U-shaped associations were observed between potassium levels and both kidney events and all-cause mortality on univariate Cox regression analyses. After adjustment for covariates, both hypokalemia and hyperkalemia were significantly associated with an increased risk of kidney events, with the lowest risk at a serum potassium of 4.0-4.4 mmol/L. Compared with a reference level of 4.0-4.4 mmol/L, the adjusted hazard ratio for kidney events was 2.49 (1.33-4.66) for serum potassium < 4.0 mmol/L, 1.72 (1.00-2.96) for 4.5-4.9 mmol/L, and 2.16 (1.15-4.06) for ≥ 5.0 mmol/L. There was no significant association between serum potassium levels and mortality after multivariate adjustment. CONCLUSION: Hypokalemia and hyperkalemia were associated with an increased risk of CKD progression, but not with mortality in Japanese patients with non-dialysis-dependent CKD.

The distribution of eGFR by age in a community-based healthy population: the Japan specific health checkups study (J-SHC study).

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.

Higher cardiovascular mortality in men with persistent dipstick hematuria.

BACKGROUND: We previously reported that dipstick hematuria (UH) was associated with higher all-cause mortality in men, but not in women. We extended the observation and examined the causes of death using repeated urinalysis in men. METHODS: Subjects were those who participated the Tokutei-Kenshin between 2008 to 2015 in seven districts. Using National database of death certificate, we identified those who might have died and confirmed further with the collaborations of the regional National Health Insurance agency and public health nurses. Dipstick results of 1 + and higher were defined as hematuria. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using the Cox proportional hazard analysis. We adjusted for age, body mass index, eGFR, proteinuria, comorbid condition (diabetes mellitus, hypertension, and dyslipidemia), past history (stroke, heart disease, and kidney disease), and lifestyle (smoking, drinking, walking, and exercise). RESULTS: A total of 170,119 men were studied and 70,350 (41.4% of the total) were re-examined next year. The prevalence of UH (-/-), UH (-/+), UH (±), and UH (+ /+) was 77.2% (N = 54,298), 14.0% (N = 9,838), 1.4% (N = 1014) and 7.4% (N = 5,200), respectively. We identified 1,162 deaths (1.7% of the total of the re-examined). The adjusted HR (95% CI) was 1.49 (1.22-1.81) for all-cause mortality and 1.83 (1.23-2.71) for cardiovascular death compared to those with UH (-/-), respectively. However, that for cancer mortality risk was not significant: 1.23 (0.92-1.64). CONCLUSIONS: In men, persistent dipstick hematuria is a significantly risk factor of all-cause mortality, in particular cardiovascular death among general screening participants.

Weight loss reduces the incidence of dipstick proteinuria: a cohort study from the Japanese general population.

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.

Evaluation of muscle quality and quantity for the assessment of sarcopenia using mid-thigh computed tomography: a cohort study.

BACKGROUND: For the diagnosis of Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP) revised the algorisms in 2019, where they added computed tomography (CT) as an assessment tool not only for quantity but also for quality in research purpose. However, the evidence for clinical appreciation of CT has been lacking. Therefore, we investigated the correlation between CT and various motor function tests to assess the utility of CT as a potential diagnostic tool for sarcopenia. METHODS: In total, 214 patients who were examined at our center during the study period (2016-2017) were included in the study. Single-slice CT scan of the mid-thigh region was performed, from which cross-sectional area (CSA) and CT attenuation value (CTV) of quadriceps femoris were evaluated for each subject. Other assessments included skeletal muscle mass index by DXA and BIA, muscle strength and physical performance. Furthermore, subjects were classified into four groups as per the Asia Working Group of Sarcopenia (AWGS) 2019 criteria as those with: normal, poor muscle function/strength (poor function), sarcopenia and severe sarcopenia. RESULTS: Knee muscle strength correlated with CSA (r = 0.60) and the correlation was significantly greater than that with DXA and BIA. For physical performance, standing-up test correlated with CSA (r = - 0.20) and CTV (r = - 0.40) and walking speed with CTV (r = 0.43), which was significantly greater than that with DXA and BIA. The CSA was significantly lower in women with sarcopenia group and in both men and women with severe sarcopenia (all p < 0.01). Furthermore, CTV was significantly lower in women with poor-function and in both men and women with severe sarcopenia group (all p < 0.01). CONCLUSIONS: CSA mostly correlated with muscle strength, whereas CTV mostly correlated with physical performance. CT with measurements of CSA and CTV enables the evaluation of muscle mass and quality simultaneously. CT is believed to be useful in inferring evaluation of motor function and assessment of sarcopenia.

Low muscle mass affect hip fracture treatment outcomes in older individuals: a single-institution case-control study.

BACKGROUND: Although sarcopenia has been known as a risk factor for hip fracture, only a few reports have described the impact of muscle mass on hip fracture treatment outcomes. The current study aimed to investigate the impact of muscle mass on hip fracture treatment outcomes. METHODS: This case-control study involved 337 patients (67 males and 270 females) with hip fracture aged ≥65 years (mean age: 84.1 ± 7.1 years) who underwent orthopedic surgery from January 2013 to June 2019. The mean follow-up period was 17.1 (1-60) months. Upon admission, all patients were assessed for low muscle mass according to the Asian Working Group for Sarcopenia criteria (male, SMI < 7.00 kg/m2; female, SMI < 5.40 kg/m2) using dual-energy X-ray absorptiometry. Treatment outcomes (stays at acute care institutions, hospital mortality, the Barthel index at discharge, and home discharge rates, and one-year mortality) were compared between patients with and without low muscle mass by Student's t-test, Mann-Whitney U test and the Pearson Chi-Square test. A multivariate logistic regression model was used to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for factors related to low muscle mass. Kaplan-Meier survival curves on one-year mortality of hip fracture patients for those with and without low muscle mass were prepared, and log-rank tests were performed. Furthermore, we determined whether low muscle mass was a risk factor for one-year mortality in hip fracture patients using a Cox proportional hazards model. RESULTS: The prevalence of low muscle mass in patients with hip fracture was 231(68.5%). Those with low muscle mass had a lower Barthel index (P < 0.0001), hospital discharge rate (P = 0.035) and higher one-year mortality (P = 0.010). Cox proportional hazards regression analysis adjusted for age and sex found that low muscle mass was a risk factor for one-year mortality (hazard ratio, 3.182, 95% confidence interval, 1.097-9.226, P = 0.033). CONCLUSIONS: Patients with hip fracture who had low muscle mass had a lower Barthel index, lower home discharge rate, and higher one-year mortality. Moreover, low muscle mass was identified as a risk factor for one-year mortality among those with hip fracture. The aforementioned findings may help clinicians better manage those with hip fracture.

Cost-Effectiveness of Behavior Modification Intervention for Patients With Chronic Kidney Disease in the FROM-J Study.

OBJECTIVES: Chronic kidney disease (CKD) is a significant public health problem. An advanced, or innovative, CKD care system of clinical practice collaboration among general physicians (GPs), nephrologists, and other healthcare workers achieved behavior modification in patients with Stage 3 CKD in the Frontier of Renal Outcome Modifications in Japan (FROM-J) study. This behavior modification intervention consisted of educational sessions on nutrition and lifestyle, as well as encouragement of patients' regular visits. The intervention contributed to slowing CKD progression. This study aimed to evaluate the cost-effectiveness of the widespread diffusion of the behavior modification intervention proven effective by the FROM-J study. METHODS: A cost-effectiveness analysis was carried out to compare the behavior modification intervention with the current practice recommended by the latest CKD clinical guidelines for GPs. A Markov model with a societal perspective under Japan's health system was constructed. We assumed that the behavior modification intervention proven effective by the FROM-J study would be initiated by GPs for targeted patient cohorts-patients aged 40-74 years with Stage 3 CKD-as a part of the innovative CKD care system. RESULTS: The incremental cost-effectiveness ratio for the behavior modification intervention compared with current guideline-based practice was calculated as 145,593 Japanese yen (¥; $1,324 United States dollars [$]) per quality-adjusted life year (QALY). CONCLUSIONS: Using the suggested value of social willingness to pay for a one-QALY gain in Japan of ¥5 million (US$45,455) as the threshold to judge cost-effectiveness, the behavior modification intervention is cost-effective. Our results suggest that diffusing the behavior modification intervention proven effective by the FROM-J study could be justifiable as an efficient use of finite healthcare resources. GPs could be encouraged to initiate this intervention by revising the National Health Insurance fee schedule and strengthening clinical guidelines regarding behavior modification interventions.