Association between glycated albumin and sudden death in patients undergoing hemodialysis.

BACKGROUND: The frequency of sudden death and its risk factors in patients undergoing hemodialysis are unknown. This study was performed to examine the association between glycated albumin (GA) and sudden death in Japanese patients undergoing hemodialysis. METHODS: In total, 260 patients undergoing hemodialysis aged ≥18 years were retrospectively followed for a mean of 4.6 years. The patients' serum GA levels were divided into tertiles, and the patients' sex, age, albumin level, C-reactive protein (CRP) level, and cardiothoracic ratio (CTR) were selected as adjustment factors. A logistic regression model was used to calculate the odds ratio (OR) for the occurrence of sudden death by GA level. RESULTS: Ninety-one patients died during follow-up. Of the 91 deaths, 23 (25.2%) were defined as sudden deaths. Compared with non-sudden death cases, sudden death cases were significantly younger (p = 0.002) and had a higher proportion of men (p = 0.03), a higher proportion of diabetes (p = 0.008), and higher GA levels (p = 0.023). Compared with patients with the lowest GA levels (<15.2%), those with the highest GA levels (≥18.5%) had a sex- and age-adjusted OR for sudden death of 5.40 [95% confidence interval (CI): 1.35-21.85]. After adjusting for the albumin level, CRP level, and CTR in addition to sex and age, the OR for sudden death of patients with the highest GA levels increased to 6.80 (95%CI: 1.64-28.08); the relationship did not change. CONCLUSION: Serum GA levels were significantly associated with sudden death in patients undergoing hemodialysis.

Swallowing dysfunction and the onset of fever in older residents with special care needs: a thirteen-month longitudinal prospective study.

A decline in swallowing function is frequently observed among older residents in nursing homes. We investigated whether swallowing dysfunction was related to the onset of fever in such individuals. Older residents aged ≥ 65 years from three nursing homes were included in this prospective study conducted from July 2017 to May 2019. The follow-up period was 13 months. The outcome was fever incidence in relation to the swallowing dysfunction. Baseline data on the activities of daily living, cognitive function, swallowing function, respiratory function, tongue pressure, and comorbidity conditions were collected. Dates on which the axillary temperature measured ay of participants was > 37.5 °C during the follow-up period were also recorded. For the statistical analyses, swallowing function assessed by the modified water swallow test (MWST) score was used to divide the participants into three groups: scores ≤ 3, 4, and 5. A total of 52 participants [median age, 89.5 years (67-104)] were enrolled. Kaplan-Meier analysis showed that the average periods until onset of fever in participants with MWST scores of ≤ 3, 4, and 5 were 8.0 (6.0-11.0), 10.0 (7.0-12.0), and 12.0 (10.0-13.0) months, respectively. Cox's proportional hazards regression model revealed that participants with an MWST score ≤ 3 were at a higher risk of fever than those with an MWST score of 5 (hazard ratio 11.5, 95% confidence interval 1.5-63.4, adjusted for possible confounders. The swallowing dysfunction correlated with the risk of fever in older residents of nursing homes.

Tongue cleaning maintains respiratory function in older individuals: A 1-year randomised controlled trial.

OBJECTIVE: The aim of this 1-year longitudinal randomised controlled trial was to evaluate the effectiveness of tongue cleaning on the maintenance of respiratory function in older adults requiring care. METHODS: The participants included 24 residents of two nursing homes in Kitakyushu, Japan. The participants were randomised to receive tongue cleaning with routine oral care (intervention group, n = 12), or routine oral care alone (control group, n = 12). Among the participants, three in the intervention group and four in the control group had cerebrovascular disease history, four in the intervention group and four in the control group had a history of cardiac disease, and five in the intervention group and four in the control group were without medical history. Respiratory function was assessed on the basis of the peak expiratory flow rate (PEFR). Tongue pressure, swallowing function, oral health status, activities of daily living and nutritional status were also measured at baseline and at the end of the 1-year follow-up period. RESULTS: The number of analysed participants in each group was 12. In the control group, the PEFR (1.6 [0.4-4.2] L s-1 vs 1.4 [0.4-3.2] L s-1 , P = .034) and tongue pressure (16.4 [1.7-35.2] kPa vs 8.0 [1.4-38.6] kPa, P = .032) significantly declined after 1-year. However, the PEFR (1.5 [0.8-2.9] L s-1 vs 1.6 [0.7-4.2] L s-1 , P = .366) and tongue pressure (18.1 [4.2-37.1] kPa vs 16.1 [5.2-41] kPa, P = .307) were maintained in the intervention group. The change in the PEFR was significantly greater in the intervention group compared with the control group (0.130 [-0.45-1.70] L s-1 vs -1.70 [-10.00-10.00] L s-1 , P = .028). CONCLUSION: Our findings suggest that tongue cleaning may help maintain tongue and respiratory function in older adults requiring care.

Reduced Estimated GFR and Cardiac Remodeling: A Population-Based Autopsy Study.

RATIONALE & OBJECTIVE: Evidence suggests that cardiac remodeling, including left ventricular hypertrophy and myocardial fibrosis, develops with progression of kidney disease. Few studies have examined cardiac pathology across a range of estimated glomerular filtration rates (eGFRs), which was the objective of this investigation. STUDY DESIGN: Population-based cross-sectional study of deceased patients undergoing autopsy. SETTING & PARTICIPANTS: 334 of 694 consecutive deceased patients undergoing autopsy with available cardiac tissue, with a prior health examination within 6 years and without a prior diagnosis of heart disease. EXPOSURE: eGFR. OUTCOMES: The thickness of the left ventricular wall, sizes of cardiac cells, and percentages of fibrosis, estimated from pathology examination of autopsy samples. ANALYTICAL APPROACH: Generalized estimating equations. RESULTS: Lower eGFRs were associated with greater left ventricular wall thickness. Deceased patients with eGFRs≥60, 45 to 59, 30 to 44, and <30mL/min/1.73m2 had left ventricular wall thicknesses of 9.1, 9.5, 9.8, and 10.3mm, respectively (P for trend<0.05). Lower eGFRs were also significantly associated with greater mean values of cardiac cell size in the left ventricular wall after adjusting for confounders: 15.3, 16.1, 16.4, and 17.4µm for eGFRs≥60, 45 to 59, 30 to 44, and <30mL/min/1.73m2 (P for trend<0.01). Patients with lower eGFRs had significantly higher multivariable-adjusted geometric mean values for fibrosis percentage in the left ventricular wall: 3.22%, 4.33%, 3.83%, and 6.14% for eGFRs≥60, 45 to 59, 30 to 44, and <30mL/min/1.73m2 (P for trend<0.001). The negative association of eGFR with multivariable-adjusted mean values of cardiac cell width was stronger among patients with than those without anemia. LIMITATIONS: Cross-sectional study with a high proportion of elderly patients, no available information for severity or duration of hypertension and other cardiovascular risk factors, no information for medication use. CONCLUSIONS: These findings suggest that reduced eGFR is associated with cardiac hypertrophy and fibrosis of the left ventricle, cardiac cell enlargement, and cardiac fibrosis.

Serum Angiopoietin-Like Protein 2 Is a Novel Risk Factor for Cardiovascular Disease in the Community: The Hisayama Study.

OBJECTIVE: Angiopoietin-like protein 2 (ANGPTL2), a proinflammatory mediator, has been reported to accelerate the development of insulin resistance, endothelial dysfunction, and atherosclerosis in mice. However, no cohort studies have examined the relationship between serum ANGPTL2 levels and the development of cardiovascular disease (CVD) in a general population. APPROACH AND RESULTS: A total of 3005 community-dwelling Japanese aged ≥40 years without a history of CVD were divided into 4 groups according to the quartiles of serum ANGPTL2 concentrations (Q1, lowest and Q4, highest) and followed up for 10 years. The hazards ratios and their 95% confidence intervals for the development of CVD (coronary heart disease or stroke) were estimated using a Cox proportional hazards model. During the follow-up, 219 first-ever CVD events were observed. The risk of CVD increased significantly with elevating ANGPTL2 levels after adjustment for age, sex, serum total cholesterol, use of lipid-lowering agents, ECG abnormalities, smoking habits, alcohol intake, and regular exercise (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.27 [0.80-2.04]; Q3, 1.48 [0.95-2.32]; and Q4, 1.85 [1.20-2.85]; P=0.003 for trend). After additional adjustment for metabolic syndrome components and serum high-sensitivity C-reactive protein levels as an inflammatory marker, the association was attenuated but remained significant (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.21 [0.76-1.94]; Q3, 1.38 [0.87-2.17]; and Q4, 1.66 [1.05-2.60]; P=0.02 for trend). CONCLUSIONS: Our findings suggest that elevated serum ANGPTL2 levels are a novel risk factor for the development of CVD in the general population. This association is partially mediated by metabolic disorders and inflammation.

The ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cancer death in a Japanese community: The Hisayama Study.

BACKGROUND: Whether the intake of eicosapentaenoic acid (EPA) or arachidonic acid (AA) affects the risk of cancer remains unclear, and the association between the serum EPA:AA ratio and cancer risk has not been fully evaluated in general populations. METHODS: A total of 3098 community-dwelling subjects aged ≥40 years were followed up for 9.6 years (2002-2012). The levels of the serum EPA:AA ratio were categorized into quartiles (<0.29, 0.29-0.41, 0.42-0.60, and >0.60). The risk estimates were computed using a Cox proportional hazards model. The same analyses were conducted for the serum docosahexaenoic acid to arachidonic acid (DHA:AA) ratio and individual fatty acid concentrations. RESULTS: During the follow-up period, 121 subjects died of cancer. Age- and sex-adjusted cancer mortality increased with lower serum EPA:AA ratio levels (P trend<0.05). In the multivariable-adjusted analysis, the subjects in the first quartile of the serum EPA:AA ratio had a 1.93-fold (95% confidence interval, 1.15-3.22) greater risk of cancer death than those in the fourth quartile. Lower serum EPA concentrations were marginally associated with higher cancer mortality (P trend<0.11), but the serum DHA or AA concentrations and the serum DHA:AA ratio were not (all P trend>0.37). With regard to site-specific cancers, lower serum EPA:AA ratio was associated with a higher risk of death from liver cancer. However, no such associations were detected for deaths from other cancers. CONCLUSIONS: These findings suggest that decreased level of the serum EPA:AA ratio is a significant risk factor for cancer death in the general Japanese population.

The Fukuoka Kidney disease Registry (FKR) Study: design and methods.

BACKGROUND: Chronic kidney disease (CKD) is an established independent risk factor for progression to end-stage renal disease (ESRD) and incidence of cardiovascular disease (CVD). The onset and progression of CKD are associated with both genetic predisposition and various lifestyle-related factors, but little is known about the influence of genetic-environmental interactions on the incidence of ESRD or CVD in patients with CKD. METHODS: The Fukuoka Kidney disease Registry (FKR) Study is designed as one of the largest prospective, multicenter, observational cohort studies in non-dialysis dependent CKD patients. The FKR Study aims to enroll approximately 5000 individuals at multiple clinical centers and follow them for up to at least 5 years. At baseline, subjects enrolled in the FKR Study will fill out extensive lifestyle-related questionnaires. Further, their health status and treatments will be monitored annually through a research network of nephrology centers. Blood and urine samples, including DNA/RNA, will be collected at the time of enrolment and every 5-years follow-up. CONCLUSIONS: The FKR Study will provide many insights into the onset and progression of CKD, which will suggest hypothesis-driven interventional clinical trials aimed at reducing the burden of CKD. The features of the FKR Study may also facilitate innovative research to identify and validate novel risk factors, including genetic susceptibility and biomarkers, using biomaterials by high-throughput omics technologies.

The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

BACKGROUND: Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. METHODS: This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. RESULTS: There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized ß = -0.30, P = 0.019). CONCLUSIONS: High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

Association of Hypertriglyceridemia With the Incidence and Progression of Chronic Kidney Disease and Modification of the Association by Daily Alcohol Consumption.

OBJECTIVE: The association of serum triglycerides (TGs) and alcohol consumption with chronic kidney disease (CKD) is unclear. The purpose of this study was to investigate the association of serum TG and daily alcohol consumption with CKD in the general population. DESIGN: The design of the study was longitudinal cohort study. SUBJECTS: Male (n = 47,737) and female (n = 69,542) participants were grouped into quartiles based on serum TG levels. MAIN OUTCOME MEASURES: We examined the associations of serum TG with annual changes in estimated glomerular filtration rate (eGFR) in all participants, the incident CKD in participants without CKD, and the progression of CKD in participants with CKD. We also examined the association of alcohol consumption with these factors and whether daily alcohol consumption alters the association of serum TG with renal prognosis. RESULTS: The higher quartile of serum TG at baseline was significantly associated with a greater decline in eGFR during the 2-year study period in all participants, even after adjustment for confounding factors. Serum TG was also significantly associated with the incidence and progression of CKD after 2 years in participants with and without CKD at baseline, respectively. Moreover, daily alcohol consumption was protectively associated with these outcomes. Stratified analysis according to the alcohol consumption status revealed that daily alcohol consumption modified the association of high TG with eGFR and CKD. CONCLUSION(S): Elevated serum TG was associated with the decline in eGFR and the incidence and progression of CKD. In addition, these associations were modified by daily alcohol consumption in this Japanese population.

Serum Uric Acid as a Risk Factor for Chronic Kidney Disease in a Japanese Community　- The Hisayama Study.

BACKGROUND: Growing evidence suggests that high serum uric acid (SUA) levels are causally related to increased risk of chronic kidney disease (CKD). However, few studies have investigated the influence of elevated SUA levels on the incidence of kidney dysfunction and albuminuria separately in community-based populations. METHODS AND RESULTS: A total of 2,059 community-dwelling Japanese subjects aged ≥40 years without CKD were followed for 5 years. CKD was defined as kidney dysfunction (estimated glomerular filtration rate <60 ml/min/1.73 m(2)) or albuminuria (urine albumin-creatinine ratio ≥30 mg/g). The odds ratio (OR) for the development of CKD was estimated according to quartiles of SUA (≤4.0, 4.1-4.9, 5.0-5.8, and ≥5.9 mg/dl). During the follow-up, 396 subjects developed CKD, of whom 125 had kidney dysfunction and 312 had albuminuria. The multivariable-adjusted risk of developing CKD increased with higher SUA levels (OR 1.00 [reference] for ≤4.0, 1.21 [95% confidence interval, 0.84-1.74] for 4.1-4.9, 1.47 [1.01-2.17] for 5.0-5.8, and 2.10 [1.37-3.23] for SUA ≥5.9 mg/dl, respectively). Similarly, there were positive associations between SUA level and the adjusted risk of developing kidney dysfunction (OR 1.00 [reference], 2.30 [1.10-4.82], 2.81 [1.34-5.88], and 3.73 [1.65-8.44]) and albuminuria (1.00 [reference], 1.12 [0.76-1.65], 1.35 [0.90-2.03], and 1.81 [1.14-2.87], respectively). CONCLUSIONS: Higher SUA levels were a significant risk factor for the development of both kidney dysfunction and albuminuria in a general Japanese population. (Circ J 2016; 80: 1857-1862).

The long-term association between physical activity and risk of dementia in the community: the Hisayama Study.

We investigated the long-term influence of physical activity on the risk of dementia in an elderly Japanese population. A total of 803 community-dwelling elderly Japanese individuals without dementia aged ≥65 years were followed prospectively for 17 years. Physically active status was defined as engaging in exercise at least one or more times per week during leisure time, and participants were divided into an active group and an inactive group by the presence or absence of such physical activity. The risk estimates of physical activity on the development of all-cause dementia and its subtypes were computed using a Cox proportional hazards model. During the follow-up, 291 participants developed all-cause dementia. Of these, 165 had Alzheimer's disease (AD), 93 had vascular dementia (VaD), and 47 had other dementia. Compared with the inactive group, the active group showed significantly lower crude incidence of AD (21.8 vs. 14.2 per 1000 person-years, p = 0.01), but no significant differences were observed for all-cause dementia (35.6 vs. 30.5, p = 0.17), VaD (11.3 vs. 9.8, p = 049), and other dementia (4.6 vs. 7.1, p = 0.15). After adjusting for potential confounders, the relationship between physical activity and risk of AD remained significant (adjusted hazard ratio 0.59, 95% confidence interval 0.41-0.84, p = 0.003). Our findings suggest that physical activity reduces the long-term risk of dementia, especially AD, in the general Japanese population.

Combination of Helicobacter pylori Antibody and Serum Pepsinogen as a Good Predictive Tool of Gastric Cancer Incidence: 20-Year Prospective Data From the Hisayama Study.

BACKGROUND: There is little information regarding whether the combination of Helicobacter pylori (H. pylori) antibody and serum pepsinogen (sPG), which is a marker of the degree of atrophic gastritis, has a discriminatory ability for detecting incident gastric cancer. We examined this issue in a long-term prospective cohort study of a Japanese population. METHODS: A total of 2446 Japanese community-dwelling individuals aged ≥40 years were stratified into four groups according to baseline H. pylori serological status and sPG: Group A (H. pylori[-], sPG[-]), Group B (H. pylori[+], sPG[-]), Group C (H. pylori[+], sPG[+]), and Group D (H. pylori[-], sPG[+]), and participants were followed up prospectively for 20 years. RESULTS: During the follow-up, 123 subjects developed gastric cancer. Compared with that in Group A, the cumulative incidence of gastric cancer was significantly increased in Groups B, C, and D, whereas no significant difference was found between Groups C and D. The multivariable-adjusted risk of gastric cancer was significantly increased in Group B (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.62-10.28) and in Groups C and D combined (HR 11.1; 95% CI, 4.45-27.46). When the multivariable model with H. pylori antibody was changed into that with the combination of H. pylori antibody and sPG, the C statistics for developing gastric cancer increased significantly (0.773 vs 0.732, P = 0.005), and the continuous net reclassification improvement value was 0.591 (P < 0.001). CONCLUSIONS: Our findings suggest that the combination of H. pylori antibody and sPG is a useful tool for predicting the development of gastric cancer.

Pathological sub-analysis of a multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy versus steroid pulse monotherapy in patients with immunoglobulin A nephropathy.

BACKGROUND: The IgA nephropathy (IgAN) Study Group in Japan conducted a multicenter, randomized, controlled trial of tonsillectomy with steroid pulse therapy (TSP) versus steroid pulse monotherapy in patients with IgAN (UMIN Clinical Trial Registry Number; C000000384). The effects of therapies in relation to pathological severity were analyzed in this study. METHODS: The patients with IgAN, urinary protein 1.0-3.5 g/day, serum creatinine of 1.5 mg/dl or less were randomly assigned to receiving TSP (Group A) or steroid pulses alone (Group B). The primary endpoint was the disappearance of proteinuria and/or hematuria. Twenty-six biopsies in Group A and 33 in Group B were available. The histological grades (HG) according to the percentage of glomeruli with crescent or sclerosis and the Oxford classification were analyzed. RESULTS: The patients in Group A had a 4.32- to 12.1-fold greater benefit of disappearance of proteinuria and 3.61- to 8.17-fold greater benefit of clinical remission (disappearance of proteinuria and hematuria) than those in Group B in patients with HG2-3, acute lesions (cellular or fibrocellular crescent) affecting more than 5 % of glomeruli, chronic lesions (fibrous crescents or sclerosis) affecting more than 20 % and S1. In contrast, odds ratios for disappearance of proteinuria or clinical remission in Group A to Group B were not significant in patients with HG 1, acute lesion in 5 % or less of glomeruli, chronic lesion in 20 % or less and S0. The disappearance of hematuria showed no relation to pathological severity. CONCLUSION: TSP might be better employed according to the pathological severity.

The effect of renin-angiotensin system blockade on the incidence of end-stage renal disease in IgA nephropathy.

BACKGROUND: The impact of renin-angiotensin system blockade (RASB) on the incidence of end-stage renal disease (ESRD) remains unclear in IgA nephropathy (IgAN). METHODS: This study assessed associations between RASB treatment and the incidence of ESRD in IgAN using propensity score approaches. We retrospectively analyzed 1273 patients with IgAN biopsied between 1979 and 2010. Propensity scores were calculated using logistic regression. Associations between RASB and ESRD were examined using a Cox regression model adjusted by inverse probability of treatment weighted, regression, stratification and matching. RESULTS: During follow-up (median 5.1 years), 130 patients developed ESRD. With Cox regression adjusted by inverse probability of treatment weighted, RASB use was significantly associated with a lower risk of ESRD (hazard ratio 0.58; 95 % confidence interval 0.42-0.80). Significant associations were observed for other propensity score-based approaches. In stratified analysis, a beneficial association between RASB and ESRD was observed in patients ≥35 years, with hypertension, reduced estimated glomerular filtration rate (<60 mL/min/1.73 m2), mesangial proliferation and segmental glomerulosclerosis (P for interaction <0.05), and tended to be greater in patients with proteinuria (≥1.0 g/24 h), extracapillary proliferation and receiving methylprednisolone pulse therapy (P for interaction <0.10). CONCLUSION: Treatment with RASB was associated with a lower incidence of ESRD in the real-world practice of IgAN.

Brain atrophy in peritoneal dialysis and CKD stages 3-5: a cross-sectional and longitudinal study.

BACKGROUND: Brain atrophy has been reported in patients with end-stage renal disease receiving hemodialysis, although its mechanism is unknown. However, little is known regarding brain atrophy in patients receiving peritoneal dialysis (PD). Therefore, we examined brain volume and its annual change over 2 years in PD patients compared with patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). STUDY DESIGN: Cross-sectional and longitudinal cohort. SETTING & PARTICIPANTS: 62 PD patients and 69 patients with NDD-CKD with no history of cerebrovascular disease who underwent brain magnetic resonance imaging (MRI) were recruited in a cross-sectional study. Among them, 34 PD patients and 61 patients with NDD-CKD, who underwent a second brain MRI after 2 years, were recruited in a longitudinal study. PREDICTOR: PD therapy versus NDD-CKD. OUTCOMES & MEASUREMENTS: T1-weighted magnetic resonance images were analyzed. Total gray matter volume (GMV), total white matter volume (WMV), and cerebrospinal fluid space volume were segmented, and each volume was quantified using statistical parametric mapping software. Normalized GMV and WMV values were calculated by division of GMV and WMV by intracranial volume to adjust for variations in head size. We compared normalized GMV and normalized WMV between PD patients and patients with NDD-CKD in the cross-sectional study and the annual change in normalized GMV in the longitudinal study. RESULTS: In the cross-sectional study, normalized GMV, which was correlated inversely with age, was lower in PD patients than in patients with NDD-CKD. However, normalized WMV, which was not correlated with age, was comparable between the groups. Annual change in normalized GMV was significantly higher in PD patients than in patients with NDD-CKD. These differences remained significant even after adjustment for potential confounding factors. LIMITATIONS: A short observation period and high dropout rate in the longitudinal study. CONCLUSIONS: Decline in normalized GMV is faster in PD patients than in patients with NDD-CKD.

Impact of the Triglycerides to High-Density Lipoprotein Cholesterol Ratio on the Incidence and Progression of CKD: A Longitudinal Study in a Large Japanese Population.

BACKGROUND: The impact of the triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) ratio on chronic kidney disease (CKD) is unclear. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: 124,700 participants aged 39 to 74 years in the Japanese Specific Health Check and Guidance System, including 50,392 men, 74,308 women, 102,900 without CKD, and 21,800 with CKD. PREDICTOR: Quartiles of TG:HDL-C ratio. OUTCOMES & MEASUREMENTS: Changes in estimated glomerular filtration rate (eGFR) and urinary protein excretion during the 2-year study period. Incident CKD in participants without CKD, and progression of CKD in participants with CKD. RESULTS: In the entire study population, higher quartile of TG:HDL-C ratio at baseline was significantly associated with greater decline in eGFR and increase in urinary protein excretion during the 2-year study period, even after adjustment for confounding factors. A higher ratio was associated with higher risk of incident CKD in participants without CKD and higher risk of rapid decline in eGFR and increase in urinary protein excretion in participants with CKD. Higher TG:HDL-C ratio was more strongly associated with decline in eGFR (P for interaction = 0.002) and with incident CKD (P for interaction = 0.05) in participants with diabetes than without diabetes. LIMITATIONS: Short observation period and single measurement of all variables. CONCLUSIONS: A higher TG:HDL-C ratio affects the decline in eGFR and incidence and progression of CKD in the Japanese population.

Prognostic impact of serum bilirubin level on long-term renal survival in IgA nephropathy.

BACKGROUND: Serum bilirubin has been recognized as a novel endogenous antioxidant. The aim of our study was to evaluate the impact of serum bilirubin on kidney prognosis in IgA nephropathy (IgAN). METHODS: We followed retrospectively 694 patients with IgAN diagnosed by renal biopsy between 1982 and 2010. The risk factors for developing end-stage renal disease (ESRD) were estimated using a Cox proportional hazard model. Predictive performance between models with or without serum bilirubin was evaluated by calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: Seventy-seven patients developed ESRD during the median 4.9 years of follow-up. Estimated glomerular filtration rate, proteinuria and histological severity were inversely related to bilirubin levels. In multivariate analysis, serum bilirubin was an independent risk factor for ESRD (hazard ratio for every 0.1 mg/dL decrease in serum bilirubin, 1.18; 95 % CI, 1.04-1.33). The incidence rate of ESRD decreased linearly with the increases in bilirubin levels (P for trend <0.01). When bilirubin was incorporated into a model with conventional ESRD risk factors, the NRI and IDI were 0.281 (P = 0.02) and 0.019 (P = 0.01), respectively. CONCLUSIONS: We demonstrated that lower bilirubin levels were significantly associated with higher risk of ESRD in IgAN. In addition, bilirubin provided incremental predictive value in the risk assessment for progression of IgAN beyond that provided by standard risk factors.

The association between objective tongue color and endoscopic findings: results from the Kyushu and Okinawa population study (KOPS).

BACKGROUND: The relation between tongue color and gastroesophageal disease is unclear. This study was done to investigate the associations between tongue color (TC), endoscopic findings, Helicobacter.pylori infection status, and serological atrophic gastritis (SAG). METHODS: The participants were 896 residents of Ishigaki Island, Okinawa, aged 28-86 years. The tongue was photographed, esophagogastroduodenoscopy was done, and serum antibody to H.pylori was measured. SAG was defined as a serum Pepsinogen (PG)Ilevel ≤70 ng/ml and a PGI/IIratio ≤3.0. TC was measured by the device-independent international commission on Illumination 1976 L*a*b* color space standards at four points: (1) edge, (2) posterior, (3) middle, and (4) apex. We also calculated the ratio of the tongue edge to the three other measured points to examine the association between the coating of the tongue and the endoscopic and laboratory findings. RESULTS: Participants were excluded who had two or more endoscopic findings (n = 315) or who had SAG without seropositivity to H.pylori (n = 33). The remaining 548 participants were divided into three groups: SAG and seropositive to H.pylori (n = 67), seropositive to H.pylori alone (n = 56), and without SAG and seronegative for H.pylori (n = 425). We divided 425 residents into a single endoscopic finding positive group (n = 207) and a negative group, which served as a control (n = 218). The most frequent single endoscopic finding was esophageal hernia (n = 110), followed by erosive esophagitis (n = 35) and erosive gastritis (EG) (n = 45). EH was significantly associated with TC (2b*/1b*) (P < 0.05). EG was significantly associated with TC (3a*, 3b*) (P < 0.05). Seropositivity to H.pylori was significantly associated with TC (3 L*, 3 L*/1 L*) (P < 0.05, <0.01), and seropositivity to both H.pylori and SAG was significantly associated with TC (3 L*/1 L*) (P < 0.05). Multivariate analysis extracted TC (3a*, 3b*) as an independent factor associated with a differential diagnosis of EG (Odds ratio (OR) 2.66 P = 0.008, OR 2.17 P = 0.045). CONCLUSIONS: The tongue body color of the middle area reflects acute change of gastric mucosa, such as erosive gastritis. Tongue diagnosis would be a useful, non-invasive screening tool for EG.

Secular trends in cardiovascular disease and its risk factors in Japanese: half-century data from the Hisayama Study (1961-2009).

BACKGROUND: Changes in lifestyle and advances in medical technology during the past half century are likely to have affected the incidence and mortality of cardiovascular disease and the prevalence of its risk factors in Japan. METHODS AND RESULTS: We established 5 cohorts consisting of residents aged ≥40 years in a Japanese community, in 1961 (n=1618), 1974 (n=2038), 1983 (n=2459), 1993 (n=1983), and 2002 (n=3108), and followed up each cohort for 7 years. The age-adjusted incidence of stroke decreased greatly, by 51% in men and by 43% in women, from the 1960s to the 1970s, but this decreasing trend slowed from the 1970s to the 2000s. Among the stroke subtypes, ischemic stroke in both sexes and intracerebral hemorrhage in men showed a similar pattern. Stroke mortality decreased as a result of the decline in incidence and a significant improvement in survival rate. Although the incidence of acute myocardial infarction did not change in either sex, disease mortality declined slightly in women. From the 1960s to the 2000s, blood pressure control among hypertensive individuals improved significantly and the smoking rate decreased, but the prevalence of glucose intolerance, hypercholesterolemia, and obesity increased steeply. CONCLUSIONS: Our findings suggest that in Japanese, the decreasing trends in the incidence of ischemic stroke have recently slowed down, and there has been no clear change in the incidence of acute myocardial infarction, probably because the benefits of hypertension control and smoking cessation have been negated by increasing metabolic risk factors.

Serum 1,25-dihydroxyvitamin d and the development of kidney dysfunction in a Japanese community.

BACKGROUND: Recent evidence indicates that vitamin D deficiency is associated with an increased risk of renal impairment, but studies addressing the influence of vitamin D deficiency on the development of chronic kidney disease (CKD) in the general Asian population have been few. METHODS AND RESULTS: A total of 2,417 community-dwelling individuals without CKD stage 3-5 aged ≥40 years were followed for 5 years (mean age, 60 years; women, 59.1%). The cumulative incidence of CKD stage 3-5, defined as estimated glomerular filtration rate (eGFR) <60ml·min(-1)·1.73m(-2), and the rate of decline in eGFR according to quartile of serum 1,25-dihydroxyvitamin D (1,25(OH)2D), were estimated. During follow-up, 378 subjects experienced CKD stage 3-5. The age- and sex-adjusted incidence of CKD stage 3-5 increased significantly with decreasing serum 1,25(OH)2D (P for trend <0.001). Compared with the highest quartile, the multivariate-adjusted odds ratio for the development of CKD stage 3-5 was 1.90 in the lowest quartile and 1.74 in the second lowest quartile, after adjusting for confounding factors. Additionally, lower serum 1,25(OH)2D was significantly associated with a greater change in eGFR (-0.10ml·min(-1)·1.73m(-2)·year(-1) per 10-pg/ml decrement in serum 1,25(OH)2D). CONCLUSIONS: Lower serum 1,25(OH)2D is a significant risk factor for the development of CKD stage 3-5 in the general Asian population.