UCP2 polymorphisms, daily step count, and number of teeth associated with all-cause mortality risk in Sado City: A hospital-based cohort study.

Objective: Uncoupling protein 2 (UCP2) is an ion/anion transporter in the mitochondrial inner membrane that plays a crucial role in immune response, regulation of oxidative stress, and cellular metabolism. UCP2 polymorphisms are linked to chronic inflammation, obesity, diabetes, heart disease, exercise efficiency, and longevity. Daily step count and number of teeth are modifiable factors that reduce mortality risk, although the role of UCP2 in this mechanism is unknown. This study aimed to assess the possible effects of UCP2 polymorphisms on the association between daily step count and number of teeth with all-cause mortality. Methods: This study was conducted as a cohort project involving adult Japanese outpatients at Sado General Hospital (PROST). The final number of participants was 875 (mean age: 69 y). All-cause mortality during thirteen years (from June 2008 to August 2021) was recorded. The functional UCP2 genotypes rs659366 and rs660339 were identified using the Japonica Array®. Survival analyses were performed using multivariate Cox proportional hazard models. Results: There were 161 deaths (mean observation period: 113 months). Age, sex, daily step count, and the number of teeth were significantly associated with mortality. In females, UCP2 polymorphisms were associated with mortality independent of other factors (rs659366 GA compared to GG + AA; HR = 2.033, p = 0.019, rs660339 C T compared to CC + TT; HR = 1.911, p = 0.029). Multivariate models, with and without UCP2 genotypes, yielded similar results. The interaction terms between UCP2 genotype and daily step count or number of teeth were not significantly associated with mortality. Conclusion: The effects of UCP2 polymorphisms on the association between daily step count or the number of teeth and all-cause mortality were not statistically significant. In females, UCP2 polymorphisms were significantly associated with all-cause mortality. Our findings confirmed the importance of physical activity and oral health and suggested a role of UCP2 in mortality risk independently with those factors.

Trends in the Incidence of Renal Replacement Therapy due to Rapidly Progressive Glomerulonephritis in Japan, 2006-2021.

Objective Patients with rapidly progressive glomerulonephritis (RPGN) are at a high risk of progression to end-stage kidney disease (ESKD), requiring renal replacement therapy (RRT). The present study examined recent trends in the incidence of RRT due to RPGN in Japan. Methods The number of patients with incident RRT due to RPGN by sex from 2006 to 2021 was extracted from the Japanese Society of Dialysis Therapy Registry. The incidence rates of RRT were calculated for four-year periods with the census population as the denominator. Standardized incidence ratios (SIRs) and age-specific incidence rates were also calculated. Results From 2006 to 2021, the crude number of patients with incident RRT due to RPGN increased by 34% and 58% in men and women, respectively. The SIRs decreased significantly in 2010-2013 relative to the first period (2006-2009) for both men (0.90 [95% confidence interval {CI} 0.85-0.96]) and women (0.92 [0.86-0.99]) but then increased to 1.01 (0.96-1.07) for men and 1.20 (1.13-1.27) for women in 2018-2021. In the older age groups (≥70 years old), age-specific incidence rates initially decreased in 2010-2013 but increased thereafter, peaking in 2018-2021. Conclusion From 2006 to 2021, the number of patients with incident RRT due to RPGN increased, with an increase in the age-specific incidence of RRT due to RPGN in the older age groups (≥70 years old), suggesting that the number of patients with incident RRT due to RPGN will continue to increase as the population ages in Japan.

Higher participation rates for specific health checkups are associated with a lower incidence of treated ESKD in Japan.

BACKGROUND: A Japanese cohort study previously reported that not attending health checkups was associated with an increased risk of treated end-stage kidney disease (ESKD). The present study aimed to examine this association at the prefecture level. METHODS: We conducted an ecological study of all prefectures in Japan (n = 47) using five sources of nationwide open data. We explored associations of participation rates for Specific Health Checkups (SHC participation rates), the estimated prevalence of chronic kidney disease (CKD), and the ratio of nephrology specialists for each prefecture with prefecture-specific standardized incidence rates (SIRs) of treated ESKD using structural equation modeling. RESULTS: Prefecture-specific SHC participation rates ranged from 44.2% to 65.9%, and were negatively correlated with prefecture-specific SIRs and prevalence of CKD, and positively correlated with the ratio of nephrology specialists. SHC participation rates had significant negative effects on prefecture-specific SIRs (standardized estimate (ß) = - 0.38, p = 0.01) and prefecture-specific prevalence of CKD (ß = - 0.32, p = 0.02). Through SHC participation rates, the ratio of nephrology specialists had a significant indirect negative effect on prefecture-specific SIRs (ß= - 0.14, p = 0.02). The model fitted the data well and explained 14% of the variance in SIRs. CONCLUSIONS: Our findings support the importance of increasing SHC participation rates at the population level and may encourage people to undergo health checkups.

Cataract Surgery and Chronic Kidney Disease: A Hospital-based Prospective Cohort Study.

Objective Cataract and chronic kidney disease (CKD) occur with increasing frequency with age and share common risk factors including smoking, diabetes, and hypertension. We evaluated the risk of incident cataract surgery in patients with non-dialysis-dependent CKD and dialysis-dependent CKD compared to non-CKD patients, while taking into account the competing risk of death. Methods The participants included 1,839 patients from Sado General Hospital enrolled in the Project in Sado for Total Health (PROST) between June 2008 and December 2016 (54% men; mean age, 69 years). Among these patients, 50%, 44%, and 6% had non-CKD, non-dialysis-dependent CKD, and dialysis-dependent CKD, respectively. Results During a median follow-up of 5.6 years (interquartile range, 4.7-7.1), 193 participants underwent cataract surgery [18.7 (95% confidence interval (CI), 16.2 - 21.5)/1,000 person-years] and 425 participants died without undergoing cataract surgery [41.0 (95% CI, 37.4 - 45.2)/1,000 person-years]. The cumulative incidence of cataract surgery was the highest in the dialysis-dependent CKD group, followed by the non-dialysis-dependent CKD and non-CKD groups (log-rank p=0.002). After adjusting for potential confounding factors, the dialysis-dependent CKD group (hazard ratio (HR) 2.48; 95% CI 1.43-4.31), but not the non-dialysis-dependent CKD group (HR, 1.01; 95% CI 0.74-1.38), had a higher risk of cataract surgery than the non-CKD group. However, this association was no longer significant according to a competing risk analysis (sub-hazard ratio, 1.67; 95% CI 0.93-3.03). Conclusion Dialysis-dependent CKD patients were found to have an increased risk of cataract surgery; however, the association was attenuated and no longer significant when death was considered a competing risk.

A Dose-Dependent Association between Alcohol Consumption and Incidence of Proteinuria and Low Glomerular Filtration Rate: A Systematic Review and Meta-Analysis of Cohort Studies.

Previous cohort studies have reported conflicting associations between alcohol consumption and chronic kidney disease, characterized by proteinuria and low glomerular filtration rate (GFR). This systematic review, which included 14,634,940 participants from 11 cohort studies, assessed a dose-dependent association of alcohol consumption and incidence of proteinuria and low estimated GFR (eGFR) of <60 mL/min/1.73 m2. Compared with non-drinkers, the incidence of proteinuria was lower in drinkers with alcohol consumption of ≤12.0 g/day (relative risk 0.87 [95% confidence interval 0.83, 0.92]), but higher in drinkers with alcohol consumption of 36.1-60.0 g/day (1.09 [1.03, 1.15]), suggesting a J-shaped association between alcohol consumption and the incidence of proteinuria. Incidence of low eGFR was lower in drinkers with alcohol consumption of ≤12.0 and 12.1-36.0 than in non-drinkers (≤12.0, 12.1-36.0, and 36.1-60.0 g/day: 0.93 [0.90, 0.95], 0.82 [0.78, 0.86], and 0.89 [0.77, 1.03], respectively), suggesting that drinkers were at lower risk of low eGFR. In conclusion, compared with non-drinkers, mild drinkers were at lower risk of proteinuria and low eGFR, whereas heavy drinkers had a higher risk of proteinuria but a lower risk of low eGFR. The clinical impact of high alcohol consumption should be assessed in well-designed studies.

Birth cohort effects in incident renal replacement therapy in Japan, 1982-2021.

BACKGROUND: This study aimed to investigate the long-term trends of incident end-stage kidney disease (ESKD) requiring renal replacement therapy (RRT) in Japan using age-period-cohort analysis and evaluated birth cohort effects for incident ESKD requiring RRT. METHODS: The number of incident RRT patients aged between 20 and 84 years by sex from 1982 to 2021 was extracted from the Japanese Society of Dialysis Therapy registry data. Annual incidence rates of RRT were calculated using census population as denominators, and changes in the incidence rates were evaluated using an age-period-cohort model. The age and survey year period categories generated 20 birth cohorts with 5-year intervals (from 1902-1907 to 1997-2001). RESULTS: The incidence rates of RRT in both sexes initially rose in the birth cohorts born in the early 1900s, and then decelerated and peaked during 1940-1960s in men and 1930-1940s in women, following a steady decline in both sexes. Compared with the reference 1947-1951 birth cohort, the highest cohort rate ratio was 1.14 (95% CI, 1.04-1.25) in the 1967-1971 birth cohort in men and 1.04 (95% CI, 0.98-1.10) in the 1937-1941 birth cohort in women. CONCLUSIONS: Significant cohort effects were identified in both sexes, but the peak of RRT was different for each sex. Our findings suggest that men born between 1940 and 1960s and women born between 1930 and 40 s may be important target populations to consider when decreasing incidence rates of RRT among the general Japanese population.

Vegetable and Fruit Intake Frequency and Mortality in Patients With and Without Chronic Kidney Disease: A Hospital-Based Cohort Study.

OBJECTIVE: Patients with advanced chronic kidney disease (CKD) are generally discouraged from consuming high amounts of vegetables and fruits given the potential risk of hyperkalemia. In the general population, however, lower vegetable and fruit intake is associated with higher mortality. This Japanese hospital-based prospective cohort study including non-CKD and CKD participants examined whether the frequency of vegetable and fruit intake is associated with mortality, and whether the presence of CKD modifies this association. METHODS: Participants were 2,006 patients who visited the outpatient department of a general hospital between June 2008 and December 2016 (55% men; mean age, 69 years). Among these participants, 902 (45%) and 131 (7%) were non-dialysis-dependent patients with CKD and hemodialysis patients, respectively. The frequency of vegetable and fruit intake was determined by a self-report questionnaire using an ordinal scale, "never or rarely," "sometimes," and "every day." Multivariable Cox proportional hazards analysis was conducted, adjusting for potential confounders. RESULTS: Vegetable and fruit intake frequency decreased with worsening CKD stage (P for trend < .001). Baseline serum potassium levels stratified by CKD stage were similar across the three vegetable and fruit intake frequency groups. During a median follow-up of 5.7 years, 561 participants died (47.1/1,000 person-years). Adjusted hazard ratios relative to the "every day" group were 1.25 (95% confidence interval, 1.04-1.52) and 1.60 (95% confidence interval, 1.23-2.08) for the "sometimes" and "never or rarely" groups, respectively, after adjusting for demographic factors, comorbidities, and CKD status. When stratified by CKD status, a similar, albeit non-significant, dose-dependent relationship was observed between vegetable and fruit intake frequency and all-cause mortality irrespective of CKD status, with no effect modification by CKD status (Pinteraction = .69). CONCLUSION: A lower frequency of vegetable and fruit intake is significantly associated with a higher risk of death regardless of CKD status.

Trends in the incidence of renal replacement therapy by type of primary kidney disease in Japan, 2006-2020.

AIM: Age-standardized incidence of end stage kidney disease requiring renal replacement therapy (RRT) has stabilized in men and declined in women in Japan since 1996. However, recent trends by primary kidney disease are unknown. The present study aimed to examine recent trends in incidence rates of RRT by primary kidney disease in Japan. METHODS: Numbers of incident RRT patients aged ≥20 years by sex and primary kidney disease from 2006 to 2020 were extracted from the Japanese Society of Dialysis Therapy registry. Using the census population as the denominator, annual incidence rates of RRT were calculated and standardized to the WHO World Standard Population (2000-2025). Average annual percentage change (AAPC) and corresponding 95% confidence intervals (CIs) were calculated for trends using Joinpoint regression analysis. RESULTS: From 2006 to 2020, the crude number of incident RRT patients due to nephrosclerosis increased by 132% for men and 62% for women. Age-standardized incidence rates of RRT due to nephrosclerosis increased significantly, by 3.3% (95% CI: 2.9-3.7) and 1.4% (95% CI: 0.8-1.9) per year for men and women, respectively. The AAPC of chronic glomerulonephritis (-4.4% [95% CI: -5.3 to -3.8] for men and -5.1% [95% CI: -5.5 to -4.6] for women) and diabetic nephropathy (-0.6% [95% CI: -0.9 to -0.3] for men and -2.8% [95% CI: -3.1 to -2.6] for women) significantly decreased from 2006 to 2020. CONCLUSION: Incident RRT due to chronic glomerulonephritis and diabetic nephropathy decreased, while the number and incident rates of RRT due to nephrosclerosis increased, from 2006 to 2020 in Japan.

Prefecture-specific prevalence of overweight/obesity is associated with regional variation in the incidence of treated ESKD in Japan.

BACKGROUND: Overweight/obesity is a significant risk factor for chronic kidney disease and end-stage kidney disease (ESKD) in the general population. This study evaluated the impact of sex- and prefecture-specific prevalence of overweight/obesity on standardized incidence rates (SIRs) of treated ESKD in Japan. METHODS: We conducted an ecological study of all prefectures in Japan (n = 47) using data from the Japanese Society of Dialysis Therapy, national census, the NDB Open Data, and the Statistics of Physicians, Dentists and Pharmacists. We calculated the prevalence of overweight/obesity and proteinuria, standardized mortality ratio, and ratio of nephrology specialists for each prefecture, and explored associations of these variables with sex- and prefecture-specific SIRs of treated ESKD using bivariate association analysis, multiple regression analysis, and structural equation modeling (SEM). RESULTS: Prefecture-specific SIRs ranged from 0.72 to 1.24 for men and 0.69-1.41 for women. Prefecture-specific SIRs were significantly correlated with both the prevalence of overweight/obesity and prevalence of proteinuria. The prevalence of overweight/obesity showed direct, positive, and significant associations with prefecture-specific SIRs in men (standardized estimate (ß) = 0.43, p < 0.001) and women (ß = 0.40, p < 0.001). The prevalence of proteinuria showed a significant association with prefecture-specific SIRs only in women (ß = 0.33, p = 0.01). The SEM models explained 26% of the variance in SIR for men and 28% for women. CONCLUSIONS: Our findings provide evidence that the prefecture-specific prevalence of overweight/obesity in Japan can explain regional variation in prefecture-specific SIRs of treated ESKD in both sexes.

Impact of adherence to CKD-MBD guidelines on mortality among Japanese dialysis patients: an ecological study.

INTRODUCTION: This study evaluated the association between prefecture-level achievement of chronic kidney disease-mineral and bone disorder (CKD-MBD) parameter targets and mortality in Japanese dialysis patients. MATERIALS AND METHODS: We conducted an ecological study of all prefectures in Japan using data from the Japanese Society of Dialysis Therapy and National Vital Statistics between 2016 and 2017. We calculated adherence rates to recommend target ranges for CKD-MBD parameters, including phosphate, corrected calcium, and parathyroid hormone (PTH), and explored associations of these rates with prefecture-specific standardized mortality rates (SMRs) among the general population and among prevalent dialysis patients using bivariate association analysis and structural equation modeling. RESULTS: Prefecture-level adherence to the target phosphate range was significantly and negatively associated with prefecture-specific SMRs in men (standardized estimate (ß) = - 0.61, p < 0.001) and women (ß = - 0.41, p < 0.001). However, prefecture-level adherence to the target corrected calcium range was significantly and negatively associated with prefecture-specific SMRs only in men (ß = - 0.28, p = 0.01). Meanwhile, prefecture-level adherence to the target PTH range was significantly and positively associated with prefecture-specific SMRs in men (ß = 0.23, p = 0.04). Prefecture-level SMRs of females in the general population had a significant impact on prefecture-level SMRs of female dialysis patients (ß = 0.27, p = 0.03). The models explained 52% of variance in SMR for men and 33% for women. CONCLUSION: A higher prefecture-level achievement rate of the target phosphate range recommended by the Japanese CKD-MBD guidelines was associated with a lower prefecture-specific SMR in the Japanese dialysis population.

Stroke incidence and chronic kidney disease: A hospital-based prospective cohort study.

AIM: This prospective cohort study aimed to (i) examine stroke incidence and stroke subtypes by chronic kidney disease (CKD) stage, (ii) examine whether CKD patients with or without proteinuria have a high risk of stroke independent of traditional cardiovascular risk factors, and (iii) determine precise estimates of stroke risk by CKD stage while accounting for competing mortality risk. METHODS: Participants were 2023 patients enrolled in the Project in Sado for Total Health between June 2008 and December 2016 (55% men; mean age, 69 years), of whom 52% had CKD (stage 1-2, 10%; G3a, 48%; G3b, 17%; G4-5, 11% and G5D, 14%). RESULTS: During a median follow-up of 5.7 years, 157 participants developed stroke and 448 died without developing stroke. Most stroke cases were ischaemic among non-dialysis-dependent CKD participants, but the relative frequency of ischaemic stroke was near that of intracerebral haemorrhage among dialysis-dependent CKD participants. After adjustment, stage 1-2 (hazard ratio [HR], 2.97; 95% confidence interval [CI], 1.60-5.51) and stage G3-5 participants with proteinuria (HR, 2.50; 95% CI, 1.56-4.02), but not stage G3-5 participants without proteinuria (HR, 0.64; 95% CI, 0.38-1.08), had a higher stroke risk compared to non-CKD participants. In competing risk analyses, the association was attenuated but remained significant. CONCLUSION: Although the distribution of stroke subtypes differed, CKD participants with proteinuria and those with CKD stage 5D had a 2- and 4-times higher risk of stroke, respectively, than that of non-CKD participants, after accounting for competing mortality risk and traditional risk factors.

Sex Differences in Cause-specific Mortality in Japanese Dialysis Patients.

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

Healthy Lifestyle and Incident Hypertension and Diabetes in Participants with and without Chronic Kidney Disease: The Japan Specific Health Checkups (J-SHC) Study.

Objective Whether or not combined lifestyle factors are associated with similar decreases in risks of incident hypertension and diabetes among individuals with and without chronic kidney disease (CKD) remains unclear. Methods This population-based prospective cohort study included participants 40-74 years old who were free from heart disease, stroke, renal failure, hypertension, diabetes, and hypercholesterolemia at baseline (n =60,234). Healthy lifestyle scores (HLSs) were calculated by adding the total number of 5 healthy lifestyle factors (non-smoking, body mass index <25 kg/m2, regular exercise, healthy eating habits, and moderate or less alcohol consumption). Cox proportional hazards models were used to examine associations between the HLS and incident hypertension or type 2 diabetes and whether or not CKD modified these associations. Results During a median of 4 years, there were 2,773 incident hypertension cases (30.1 cases per 1,000 person-years) and 263 incident diabetes cases (2.4 cases per 1,000 person-years). The risk of developing hypertension and diabetes decreased linearly as participants adhered to more HLS components. Compared with adhering to 0, 1, or 2 components, adherence to all 5 HLS components was associated with a nearly one-half reduction in the risk of hypertension [hazard ratio (HR) =0.52; 95% confidence interval (CI), 0.45-0.60] and diabetes (HR=0.51; 95% CI, 0.32-0.81) in fully adjusted models. CKD did not have a modifying effect on associations between the HLS and incident hypertension (Pinteraction=0.6) or diabetes (Pinteraction=0.3). Conclusion Adherence to HLS components was associated with reduced risks of incident hypertension and diabetes, regardless of CKD status.

Polypharmacy, chronic kidney disease, and incident fragility fracture: a prospective cohort study.

INTRODUCTION: Polypharmacy is associated with an increased risk of fracture in aging populations, but no study has accounted for the impact of kidney function on this association. This study aimed to examine the association between polypharmacy and incident fragility fracture based on chronic kidney disease (CKD) status. MATERIALS AND METHODS: Participants were 2023 patients (55% men; mean age, 69 years) of Sado General Hospital enrolled in the Project in Sado for Total Health (PROST) between June 2008 and December 2016. Among these, 65%, 28%, and 7% had non-CKD, non-dialysis-dependent CKD, and dialysis-dependent CKD, respectively. Multivariable Cox proportional hazards analysis was conducted with adjustments for potential confounders. RESULTS: Prevalences of polypharmacy (≥ 5 medications) and hyperpolypharmacy (≥ 10 medications) among participants were 43% and 9% for non-CKD, 62% and 23% for non-dialysis-dependent CKD, and 85% and 34% for dialysis-dependent CKD, respectively. During a median follow-up of 5.6 years, 256 fractures occurred. More medications were associated with a higher risk of fractures. Specifically, compared to participants without polypharmacy, adjusted hazard ratios were 1.32 (95% CI 0.96-1.79) and 1.99 (1.35-2.92) for those with polypharmacy and hyperpolypharmacy, respectively, after adjusting for osteoporosis risk factors, CKD status, and comorbidities. No effect modification by CKD status was observed (interaction P = 0.51). Population-attributable fractions of hyperpolypharmacy for fracture were 9.9% in the total cohort and 42.1% in dialysis-dependent CKD patients. CONCLUSION: Hyperpolypharmacy is associated with an increased risk of fragility fracture regardless of CKD status, and has a strong impact on incident fragility fractures in dialysis-dependent CKD patients.

Smoking and risk of fractures requiring hospitalization in haemodialysis patients: a nationwide cohort study in Japan.

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

The Effect of CKD on Associations between Lifestyle Factors and All-cause, Cancer, and Cardiovascular Mortality: A Population-based Cohort Study.

Objective Results from previous studies on the dose-dependent effect of adhering to multiple lifestyle factors on all-cause mortality in patients with chronic kidney disease (CKD) are inconsistent, despite the reported dose-dependent effect in the general population. This study aimed to examine whether CKD modifies the dose-dependent effect of adhering to multiple lifestyle factors on mortality. Methods This population-based prospective cohort study targeted 262,011 men and women aged 40-74 years at baseline. Of these, 18.5% had CKD, which was defined as GFR <60 mL/min/1.73 m2, ≥1+ proteinuria on urinalysis, or both. The following lifestyle behaviors were considered healthy: no smoking, body mass index <25 kg/m2, moderate or lower alcohol consumption, regular exercise, and healthy eating habits. Healthy lifestyle scores were calculated by adding the total number of lifestyle factors for which each participant was at low risk. Cox proportional hazards models were used to examine associations between healthy lifestyle scores and all-cause, cancer, and cardiovascular mortality, and whether CKD modified these associations. Results During a median follow-up of 4.7 years, 3,471 participants died. The risks of all-cause and cancer mortality decreased as the number of five healthy lifestyle factors that were adhered to increased, irrespective of the CKD status. The risk of cardiovascular mortality, however, was modified by CKD (interaction p=0.07), and an unhealthy lifestyle and CKD synergistically increased cardiovascular mortality. Conclusion A healthy lifestyle can reduce the risk of all-cause and cancer death in patients with or without CKD, while the prevention of CKD is essential for reducing the risk of cardiovascular death.

Association between serum IgG antibody titers against Porphyromonas gingivalis and liver enzyme levels: A cross-sectional study in Sado Island.

BACKGROUND: Previous studies have reported associations between nonalcoholic fatty liver disease, periodontitis, and obesity. Serum immunoglobulin G (IgG) antibody titer against Porphyromonas gingivalis, a major pathogen of periodontitis, is an established indicator of periodontal infection. However, the relationship between the antibody titer and liver enzyme levels has not been clarified yet. A study in the elderly was needed to evaluate the effect of long-term persistent bacterial infection on liver function. The objective of this study was to investigate the association between liver function and infection by P. gingivalis, and the effect of obesity on the association. METHODS: A cross-sectional study was conducted in adult outpatients visiting Sado General Hospital, in Niigata Prefecture, Japan, from 2008 to 2010. The final participants included 192 men and 196 women (mean age 68.1 years). Multivariable logistic regression analyses were performed to assess the association between the serum IgG antibody titer and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamine transferase (GGT) levels. RESULTS: In women, serum IgG antibody titers against P. gingivalis was associated with elevated ALT, but not with AST or GGT, independent of covariates (p = 0.015). No significant association was found between the antibody titer and the elevated liver enzymes in men. The effect of obesity on the relationship between antibody titer and liver enzyme levels was not statistically significant. CONCLUSIONS: A cross-sectional analysis of adult outpatients suggested an association between P. gingivalis infection and ALT levels in women. The effect of obesity on this association was not statistically significant.