The 21-Year Trend of Stroke Incidence in a General Japanese Population: Results from the Takashima Stroke Registry, 1990-2010.

INTRODUCTION: Since the 1960s, the stroke morality rate in Japan has declined significantly. Although several risk factors for stroke have become more evident due to increasingly Westernized lifestyle, there have been no population-based registry data on recent time trends in stroke incidence in Japan. The purpose of this study is to determine these trends in stroke incidence using a population-based registry. METHODS: Data were obtained from the Takashima Stroke Registry, which covers approximately 50,000 residents in Takashima City, Japan. The age- and sex-standardized stroke incidence rate was estimated using the direct method. Average annual relative changes of stroke incidence were estimated using Poisson regression models. RESULTS: We identified a total of 2,371 patients with first-ever stroke during the period 1990-2010. Crude incidence rates of total stroke (per 100,000 person-years) were 225 in the early period (1990-2001) and 187 in the late period (2002-2010), and the mean age at onset of stroke increased from 71.9 years in the early period to 74.8 years in the late period. Age- and sex-standardized incidence rates of stroke (per 100,000 person-years) decreased from 327 in the early part of this study period and 206 in the later period. During the 21-year period, age- and sex-standardized average annual relative reduction in stroke incidence was statistically significant (-3.7% per year). When stratified into early and late periods, the adjusted annual relative reduction in stroke incidence was observed during the early period (-2.1% per year), and there were no significant changes during the late period. CONCLUSIONS: In this population-based registry, there was a significant reduction in incidence of stroke from 1990 to 2010. Although the speed of reduction in stroke incidence appears to have slowed down after 2000, continuous public health measures are required to provide further protection against stroke.

Assessing the Relationship Between High-sensitivity C-reactive Protein and Kidney Function Employing Mendelian Randomization in the Japanese Community-based J-MICC Study.

BACKGROUND: Inflammation is thought to be a risk factor for kidney disease. However, whether inflammatory status is either a cause or an outcome of chronic kidney disease remains controversial. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using Mendelian randomization (MR) approaches. METHODS: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively. RESULTS: Using the IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 0.000; 95% confidence interval [CI], -0.019 to 0.020 and -0.003; 95% CI, -0.019 to 0.014, respectively). For IVAsian, we found similar results using the IVW and the WM methods (estimate, 0.005; 95% CI, -0.020 to 0.010 and -0.004; 95% CI, -0.020 to 0.012, respectively). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IVCRP: -0.008; 95% CI, -0.058 to 0.042; IVAsian: 0.001; 95% CI, -0.036 to 0.036). CONCLUSION: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.

Genome-Wide Association Study of Renal Function Traits: Results from the Japan Multi-Institutional Collaborative Cohort Study.

BACKGROUND: Chronic kidney disease (CKD) is a rapidly growing, worldwide public health problem. Recent advances in genome-wide-association studies (GWAS) revealed several genetic loci associated with renal function traits worldwide. METHODS: We investigated the association of genetic factors with the levels of serum creatinine (SCr) and the estimated glomerular filtration rate (eGFR) in Japanese population-based cohorts analyzing the GWAS imputed data with 11,221 subjects and 12,617,569 variants, and replicated the findings with the 148,829 hospital-based Japanese subjects. RESULTS: In the discovery phase, 28 variants within 4 loci (chromosome [chr] 2 with 8 variants including rs3770636 in the LDL receptor related protein 2 gene locus, on chr 5 with 2 variants including rs270184, chr 17 with 15 variants including rs3785837 in the BCAS3 gene locus, and chr 18 with 3 variants including rs74183647 in the nuclear factor of -activated T-cells 1 gene locus) reached the suggestive level of p < 1 × 10-6 in association with eGFR and SCr, and 2 variants on chr 4 (including rs78351985 in the microsomal triglyceride transfer protein gene locus) fulfilled the suggestive level in association with the risk of CKD. In the replication phase, 25 variants within 3 loci (chr 2 with 7 variants, chr 17 with 15 variants and chr 18 with 3 variants) in association with eGFR and SCr, and 2 variants on chr 4 associated with the risk of CKD became nominally statistically significant after Bonferroni correction, among which 15 variants on chr 17 and 3 variants on chr 18 reached genome-wide significance of p < 5 × 10-8 in the combined study meta-analysis. The associations of the loci on chr 2 and 18 with eGFR and SCr as well as that on chr 4 with CKD risk have not been previously reported in the Japanese and East Asian populations. CONCLUSION: Although the present GWAS of renal function traits included the largest sample of Japanese participants to date, we did not identify novel loci for renal traits. However, we identified the novel associations of the genetic loci on chr 2, 4, and 18 with renal function traits in the Japanese population, suggesting these are transethnic loci. Further investigations of these associations are expected to further validate our findings for the potential establishment of personalized prevention of renal disease in the Japanese and East Asian populations.

Risk of stroke and heart failure attributable to atrial fibrillation in middle-aged and elderly people: Results from a five-year prospective cohort study of Japanese community dwellers.

BACKGROUND: The relative and absolute risks of stroke and heart failure attributable to atrial fibrillation (AF) have not been sufficiently examined. METHODS: A prospective study of 23,731 community-dwelling Japanese individuals was conducted. Participants were divided into two groups based on the presence or absence of prevalent AF (n = 338 and n = 23,393, respectively). Excess events (EE) due to AF and relative risks (RRs) determined using the non-AF group as the reference for incident stroke and heart failure were estimated using Poisson regression stratified by age groups (middle-aged: 40-69 years old; elderly: 70 years of age or older) after adjustment for sex and age. RESULTS: There were 611 cases of stroke and 98 cases of heart failure during the observation period (131,088 person-years). AF contributed to a higher risk of stroke both in middle-aged individuals (EE 10.4 per 1000 person-years; RR 4.88; 95% confidence interval [CI], 2.88-8.29) and elderly individuals (EE 18.3 per 1000 person-years; RR 3.05; 95% CI, 2.05-4.54). AF also contributed to a higher risk of heart failure in middle-aged individuals (EE 3.7 per 1000 person-years; RR 8.18; 95% CI, 2.41-27.8) and elderly individuals (EE 15.4 per 1000 person-years; RR 7.82; 95% CI, 4.11-14.9). Results obtained from multivariate-adjusted analysis were similar (stroke: EE 8.9 per 1000 person-years; RR 4.40; 95% CI, 2.57-7.55 in middle-aged and EE 17.4 per 1000 person-years; RR 2.97; 95% CI, 1.99-4.43 in elderly individuals; heart failure: EE 3.1 per 1000 person-years; RR 7.22; 95% CI, 2.06-25.3 in middle-aged and EE 14.1 per 1000 person-years; RR 7.41; 95% CI, 3.86-14.2 in elderly individuals). CONCLUSIONS: AF increased the risk of stroke by the same magnitude as that reported previously in Western countries. AF increased the RR of heart failure more than that in Western populations.

Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease.

AIM: Domperidone is preferentially used over other antiemetic agents to treat digestive symptoms in Parkinson's disease (PD). Concerns have been raised regarding an increased risk of ventricular tachyarrhythmia and sudden cardiac death (VT/SCD) associated with domperidone in the general population. However, the risk in PD is unknown. METHODS: We conducted a multicentre retrospective cohort study using administrative databases from seven Canadian provinces and the UK Clinical Practice Research Datalink. Using a nested case-control analysis, we estimated the rate ratios (RRs) of VT/SCD associated with domperidone use compared to no use in patients newly-diagnosed with PD. VT/SCD events were identified using administrative medical records and vital statistics with a manual review of all potential cases. Meta-analytic methods were used to estimate overall effects across sites. RESULTS: Among 214 962 patients with PD, 2907 cases of VT/SCD were identified during 886 581 person-years of follow-up (incidence rate 3.28 per 1000 persons per year). Current use of domperidone was associated with a non-statistically significant 22% increased risk of VT/SCD (RR 1.22; 95% CI 0.99-1.50) compared with no use. The risk was significantly elevated in those with a history of cardiovascular disease (RR 1.38; 95% CI 1.07-1.78), but not in those without (RR 1.21; 95% CI 0.81-1.81). Dose and duration of use did not affect the magnitude of the risk. CONCLUSION: Domperidone use may increase the risk of VT/SCD in patients with PD, particularly those with a history of cardiovascular disease. This risk may be underestimated because of imprecision in identifying VT/SCD events.

Lifetime risk of diabetes among First Nations and non-First Nations people.

BACKGROUND: Lifetime risk is a relatively straightforward measure used to communicate disease burden, representing the cumulative risk of an outcome during the remainder of an individual's life starting from a disease-free index age. We estimated the lifetime risk of diabetes among men and women in both First Nations and non-First Nations populations using a cohort of adults in a single Canadian province. METHODS: We used a population-based cohort consisting of Alberta residents from 1997 to 2008 who were free of diabetes at cohort entry to estimate the lifetime risk of diabetes among First Nations and non-First Nations people. We calculated age-specific incidence rates with the person-year method in 5-year bands. We estimated the sex- and index-age-specific lifetime risk of incident diabetes, after adjusting for the competing risk of death. RESULTS: The cohort included 70 631 First Nations and 2 732 214 non-First Nations people aged 18 years or older. The lifetime risk of diabetes at 20 years of age was 75.6% among men and 87.3% among women in the First Nations group, as compared with 55.6% among men and 46.5% among women in the non-First Nations group. The risk was higher among First Nations people than among non-First Nations people for all index ages and for both sexes. Among non-First Nations people, men had a higher lifetime risk of diabetes than women across all index ages. In contrast, among First Nations people, women had a higher lifetime risk than men across all index ages. INTERPRETATION: About 8 in 10 First Nations people and about 5 in 10 non-First Nations people of young age will develop diabetes in their remaining lifetime. These population-based estimates may help health care planners and decision-makers set priorities and increase public awareness and interest in the prevention of diabetes.

What is the scope of improving immigrant and ethnic minority healthcare using community navigators: A systematic scoping review.

INTRODUCTION: Immigrants are among the most vulnerable population groups in North America; they face multidimensional hurdles to obtain proper healthcare. Such barriers result in increased risk of developing acute and chronic conditions. Subsequently a great deal of burden is placed on the healthcare system. Community navigator programs are designed to provide culturally sensitive guidance to vulnerable populations in order to overcome barriers to accessing healthcare. Navigators are healthcare workers who support patients to obtain appropriate healthcare. This scoping review systematically searches and summarizes the literature on community navigators to help immigrant and ethnic minority groups in Canada and the United States overcome barriers to healthcare. METHODS: We systematically searched electronic databases for primary articles and grey literature. Study selection was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Articles were selected based on four criteria: (1) the study population was comprised of immigrants or ethnic minorities living in Canada or the United States; (2) study outcomes were related to chronic disease management or primary care access; (3) the study reported effects of community navigator intervention; (4) the study was published in English. Relevant information from the articles was extracted and reported in the review. RESULT: Only one study was found in the literature that focused on navigators for immigrants in Canada. In contrast, 29 articles were found that reported navigator intervention programs for immigrant minorities in the United States. In these studies navigators trained and guided members of several ethnic communities for chronic disease prevention and management, to undertake cancer screening as well as accessing primary healthcare. The studies reported substantial improvement in the immigrant and ethnic minority health outcomes in the United States. The single Canadian study also reported positive outcome of navigators among immigrant women. CONCLUSION: Navigator interventions have not been fully explored in Canada, where as, there have been many studies in the United States and these demonstrated significant improvements in immigrant health outcomes. With many immigrants arriving in Canada each year, community navigators may provide a solution to reduce the existing healthcare barriers and support better health outcomes for new comers.

Standardized Prevalence Ratios for Atrial Fibrillation in Adult Dialysis Patients in Japan.

BACKGROUND: While it is assumed that dialysis patients in Japan have a higher prevalence of atrial fibrillation (AF) than the general population, the magnitude of this difference is not known. METHODS: Standardized prevalence ratios (SPRs) for AF in dialysis patients (n = 1510) were calculated compared to data from the general population (n = 26 454) living in the same area. RESULTS: The prevalences of AF were 3.8% and 1.6% in dialysis patients and the general population, respectively. In male subjects, these respective values were 4.9% and 3.3%, and in female subjects they were 1.6% and 0.6%. The SPRs for AF were 2.53 (95% confidence interval [CI], 1.88-3.19) in all dialysis patients, 1.80 (95% CI, 1.30-2.29) in male dialysis patients, and 2.13 (95% CI, 0.66-3.61) in female dialysis patients. CONCLUSIONS: The prevalence of AF in dialysis patients was twice that in the population-based controls. Since AF strongly contributes to a higher risk of cardiovascular mortality and morbidity in the general population, further longitudinal studies should be conducted regarding the risk of several outcomes attributable to AF among Japanese dialysis patients.

Renal function trajectory over time and adverse clinical outcomes.

The growing burden of chronic kidney disease (CKD), with its associated morbidity and mortality, is recognized as a major public health problem globally and causing substantial load on health care systems. The current framework for the definition and staging of CKD, based on eGFR levels or presence of kidney damage, is useful for clinical classification of patients, but identifies a huge number of people as having CKD which is too many to target for intervention. The ability to identify a subset of patients, at high risk for adverse outcomes, would be useful to inform clinical management. The current staging system applies static definitions of kidney function that fail to capture the dynamic nature of the kidney disease over time. Now-a-days, it is possible to capture multiple measurements of different laboratory test results for an individual including eGFR values. A new possibility for identifying individuals at higher risk of adverse outcomes is being explored through assessment and consideration of the rate of change in kidney function over time, and this approach will be feasible in the current context of digitalization of health record keeping system. On the basis of the existing evidence, this paper summarizes important findings that support the concept of dynamic changes in kidney function over time, and discusses how the magnitude of these changes affect the future adverse outcomes of kidney disease, particularly the End Stage Renal Disease (ESRD), CVD and mortality.

Assessing the Validity of Surrogate Outcomes for ESRD: A Meta-Analysis.

Validation of current and promising surrogate outcomes for ESRD in randomized controlled trials (RCTs) has been limited. We conducted a systematic review and meta-analysis of RCTs to further inform the ability of surrogate outcomes for ESRD to predict the efficacy of various interventions on ESRD. MEDLINE, EMBASE, and CENTRAL (from inception through September 2013) were searched. All RCTs in adults with proteinuria, diabetes, or CKD stages 1-4 or renal transplant recipients reporting ≥10 ESRD events and a surrogate outcome (change in proteinuria or doubling of serum creatinine [DSCR]) for ESRD during a ≥1-year follow-up were included. Two reviewers abstracted trial characteristics and outcome data independently. To assess the correlation between the surrogate outcomes and ESRD, we determined the treatment effect ratio (TER), defined as the ratio of the treatment effects on ESRD and the effects on the change in surrogate outcomes. TERs close to 1 indicate greater agreement between ESRD and the surrogate, and these ratios were pooled across interventions. We identified 27 trials (97,458 participants; 4187 participants with ESRD). Seven trials reported the effects on change in proteinuria and showed consistent effects for proteinuria and ESRD (TER, 0.82; 95% confidence interval, 0.59 to 1.16), with minimal heterogeneity. Twenty trials reported on DSCR. Treatment effects on DSCR were consistent with the effects on ESRD (TER, 0.98; 95% confidence interval, 0.85 to 1.14), with moderate heterogeneity. In conclusion, DSCR is generally a good surrogate for ESRD, whereas data on proteinuria were limited. Further assessment of the surrogacy of proteinuria using prospective RCTs is warranted.

Hospice care in Calgary: Survey of family physicians on their knowledge, experience, and attitudes.

OBJECTIVE: To explore Calgary family physicians' knowledge about hospices, their attitudes toward the referral process, and their understanding of barriers to referral for hospice care. DESIGN: Surveys were mailed to 400 randomly selected participants. The survey contained 18 questions related to hospice care, physician experience, attitudes, and perceived barriers to making a hospice referral. SETTING: Calgary, Alta. PARTICIPANTS: Family physicians. MAIN OUTCOME MEASURES: Survey responses were analyzed quantitatively using the (2) goodness-of-fit test, Kruskal-Wallis tests, and logistic regression analyses to examine univariate associations. Qualitative analysis of open-ended questions was done by content analysis and thematic coding. RESULTS: In total, 104 surveys were mailed back. Family physicians agreed that palliative care in a hospice setting can greatly improve quality of life for patients, but only 2 of 6 knowledge questions about hospice care were answered correctly by most. Family physicians with special areas of interest or subspecialties were more likely to feel well-informed about hospice referrals (P = .017), indicated a higher comfort level discussing hospice and palliative care (P = .030), and were less likely to defer discussing it with patients (P = .023). Physicians with a special interest in palliative medicine were more likely to correctly answer the knowledge questions (P < .034) and to be familiar with the referral process (P < .001), patient eligibility (P < .001), and the palliative home care program (P = .003). Qualitative analysis revealed support for palliative home care and consultation services but concerns about caregiver coping and family issues. Concerns about disengagement of family physicians and uncertainty about the referral process are obstacles to referral. CONCLUSION: While Calgary family physicians are appreciative of hospice care, there are knowledge gaps. It is important to engage family physicians in the referral process.

Social media in communicating health information: an analysis of Facebook groups related to hypertension.

INTRODUCTION: We studied Facebook groups related to hypertension to characterize their objectives, subject matter, member sizes, geographical boundaries, level of activity, and user-generated content. METHODS: We performed a systematic search among open Facebook groups using the keywords "hypertension," "high blood pressure," "raised blood pressure," and "blood pressure." We extracted relevant data from each group's content and developed a coding and categorizing scheme for the whole data set. Stepwise logistic regression was used to explore factors independently associated with each group's level of activity. RESULTS: We found 187 hypertension-related Facebook groups containing 8,966 members. The main objective of most (59.9%) Facebook groups was to create hypertension awareness, and 11.2% were created primarily to support patients and caregivers. Among the top-displayed, most recent posts (n = 164), 21.3% were focused on product or service promotion, whereas one-fifth of posts were related to hypertension-awareness information. Each Facebook group's level of activity was independently associated with group size (adjusted odds ratio [AOR], 1.02; 95% confidence interval [CI], 1.01-1.03), presence of "likes" on the most recent wall post (AOR, 3.55, 95% CI, 1.41-8.92), and presence of attached files on the group wall (AOR, 5.01, 95% CI, 1.25-20.1). CONCLUSION: The primary objective of most of the hypertension-related Facebook groups observed in this study was awareness creation. Compared with the whole Facebook community, the total number of hypertension-related Facebook groups and their users was small and the groups were less active.

A meta-analysis to derive literature-based benchmarks for readmission and hospital mortality after patient discharge from intensive care.

INTRODUCTION: We sought to derive literature-based summary estimates of readmission to the ICU and hospital mortality among patients discharged alive from the ICU. METHODS: We searched MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials from inception to March 2013, as well as the reference lists in the publications of the included studies. We selected cohort studies of ICU discharge prognostic factors that in which readmission to the ICU or hospital mortality among patients discharged alive from the ICU was reported. Two reviewers independently abstracted the number of patients readmitted to the ICU and hospital deaths among patients discharged alive from the ICU. Fixed effects and random effects models were used to estimate the pooled cumulative incidence of ICU readmission and the pooled cumulative incidence of hospital mortality. RESULTS: The analysis included 58 studies (n = 2,073,170 patients). The majority of studies followed patients until hospital discharge (n = 46 studies) and reported readmission to the ICU (n = 46 studies) or hospital mortality (n = 49 studies). The cumulative incidence of ICU readmission was 4.0 readmissions (95% confidence interval (CI), 3.9 to 4.0) per 100 patient discharges using fixed effects pooling and 6.3 readmissions (95% CI, 5.6 to 6.9) per 100 patient discharges using random effects pooling. The cumulative incidence of hospital mortality was 3.3 deaths (95% CI, 3.3 to 3.3) per 100 patient discharges using fixed effects pooling and 6.8 deaths (95% CI, 6.1 to 7.6) per 100 patient discharges using random effects pooling. There was significant heterogeneity for the pooled estimates, which was partially explained by patient, institution and study methodological characteristics. CONCLUSIONS: Using current literature estimates, for every 100 patients discharged alive from the ICU, between 4 and 6 patients on average will be readmitted to the ICU and between 3 and 7 patients on average will die prior to hospital discharge. These estimates can inform the selection of benchmarks for quality metrics of transitions of patient care between the ICU and the hospital ward.

Polymorphisms of genes involved in lipid metabolism and risk of chronic kidney disease in Japanese - cross-sectional data from the J-MICC study.

BACKGROUND: Chronic kidney disease (CKD) is known to be one of the causes of cardiovascular disease and end-stage renal disease. Among the several treatable risk factors of CKD, that of dyslipidemia is relatively controversial. To clarify the association of polymorphisms in genes involved in lipid metabolism with the risk of CKD in the Japanese population, we used cross-sectional data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. METHODS: A total of 3,268 men and women, aged 35-69 years, were selected from J-MICC Study participants for inclusion in this study. Twenty-eight candidate single nucleotide polymorphisms (SNPs) were selected in 17 genes associated with the risk of lipid metabolism disorders, and genotyping of the subjects was conducted using the multiplex PCR-based invader assay. The prevalence of CKD was determined for stages 3-5 (defined as estimated glomerular filtration rate <60 ml/min/1.73 m2). RESULTS: Logistic regression analysis revealed that SNPs APOA5 T - 1131C (rs662799), APOA5 T1259C (rs2266788), TOMM40 A/G (rs157580), and CETP TaqIB (rs708272) were significantly associated with CKD risk in those individuals genotyped, with age- and sex-adjusted odds ratios (ORs) per minor allele (and 95% confidence intervals (CIs)) of OR 1.22 (95% CI: 1.06-1.39), 1.19 (1.03-1.37), 1.27 (1.12-1.45), and 0.81 (0.71-0.92), respectively. Analysis of the gene-environment interaction revealed that body mass index (BMI) was a significant effect modifier for APOA5 T - 1131C (rs662799) and a marginally significant effect modifier for APOA5 T/C (rs2266788), with the interaction between BMI ≥30 and individuals with at least one minor allele of each genotype of OR 10.43 (95% CI: 1.29-84.19) and 3.36 (0.87-13.01), respectively. CONCLUSIONS: Four polymorphisms in APOA5, TOMM40, and CETP were shown to be significantly associated with CKD risk, and a significant interaction between the two APOA5 SNPs and BMI on CKD risk was also demonstrated. This suggests the future possibility of personalized risk estimation for this life-limiting disease.

Proteinuria and rate of change in kidney function in a community-based population.

Proteinuria identifies patients at risk for adverse clinical outcomes, but it is unclear whether proteinuria correlates with the rate of renal decline. We examined the association between proteinuria and rate of change in estimated GFR (eGFR) in a cohort of 638,150 adults from a province-wide registry in Alberta, Canada, who had a measure of proteinuria and three or more outpatient serum creatinine measurements over a period of ≥1 year. An adjusted sex-specific linear mixed-effects model was used to determine the rate of change in eGFR per year for patients with normal, mild, and heavy proteinuria, stratified by baseline kidney function (eGFR ≥90, 60-89.9, 45-59.9, 30-44.9, and 15-29.9 ml/min per 1.73 m(2)). In men, heavy proteinuria and a baseline eGFR of 45-59.9 ml/min per 1.73 m(2) correlated with a change in eGFR of -2.16 (95% confidence interval [CI], -2.37 to -1.95) ml/min per 1.73 m(2) per year, whereas mild proteinuria and a baseline eGFR of 30-44.9 ml/min per 1.73 m(2) correlated with a change in eGFR of -0.51 (95% CI, -0.70 to -0.32) ml/min per 1.73 m(2) per year. Similar trends were observed for female, elderly, and diabetic patients. Notably, normal protein levels and a lower baseline eGFR (15-29.9 ml/min per 1.73 m(2)) correlated with stable or improved renal function. In conclusion, our results suggest that proteinuria of increasing severity is associated with a faster rate of renal decline, regardless of baseline eGFR, and the combined effect should be considered in patients with CKD.

Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

Associations of marital status with mortality from all causes and mortality from cardiovascular disease in Japanese haemodialysis patients.

BACKGROUND: Marital status is an important social factor associated with increased mortality from cardiovascular disease (CVD) and all causes. However, there has been no study on the association of marital status with mortality in haemodialysis patients. METHODS: We analysed data from a 5-year prospective cohort study of 1064 Japanese haemodialysis patients aged 30 years or older. Marital status was classified into three groups: married, single and divorced/widowed. Cox's regression was used to estimate multivariate hazard ratios (HRs) [95% confidence intervals (CIs)] for all-cause mortality and CVD mortality according to marital status after adjusting for age, sex, duration of haemodialysis, cause of renal failure, body mass index, systolic blood pressure, total cholesterol, high density lipoprotein-cholesterol, albumin, high-sensitivity C-reactive protein, co-morbid conditions, smoking, alcohol consumption, education levels and job status. RESULTS: Single patients had higher risks than married patients for mortality from all causes (HR = 1.51, 95% CI: 1.06-2.16) and mortality from CVD (HR = 1.68, 95% CI: 1.03-2.76), and divorced/widowed patients had a higher risk than married patients for mortality from CVD (HR = 1.73, 95% CI: 1.15-2.60). After stratification by age, single patients aged 30-59 years had significantly higher risks for all-cause mortality and CVD mortality. CONCLUSIONS: The findings suggest that single status is a significant predictor for all-cause mortality and CVD mortality and that divorced/widowed status is a significant predictor for CVD mortality in haemodialysis patients.

Comparison of predictability of future cardiovascular events between chronic kidney disease (CKD) stage based on CKD epidemiology collaboration equation and that based on modification of diet in renal disease equation in the Japanese general population--Iwate KENCO Study.

BACKGROUND: Whether estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Study equation (eGFRCKDEPI) improves risk prediction compared to that calculated using the Modification of Diet in Renal Disease (MDRD) study equation (eGFRMDRD) has not been examined in a prospective study in Japanese people. METHODS AND RESULTS: Participants (n=24,560) were divided into 4 stages (1, ≥90; 2, 60-89 (reference); 3a, 45-59; 3b+ <45 ml·min(-1)·1.73 m(-2)) according to eGFRCKDEPI or eGFRMDRD. Endpoints were all-cause death, myocardial infarction (MI) and stroke. Area under the receiver operating characteristic curves (95% confidence intervals) for predicting all-cause death, MI and stroke by eGFRCKDEPI vs. eGFRMDRD were 0.680 (0.662-0.697) vs. 0.582 (0.562-0.602); 0.718 (0.665-0.771) vs. 0.642 (0.581-0.703); and 0.656 (0.636-0.676) vs. 0.576 (0.553-0.599), respectively. Multivariate-adjusted Cox regression and Poisson regression analysis results were similar for adjusted incidence rates and adjusted hazard ratios in each corresponding stage between the 2 models and no differences were found in model assessment parameters. Net reclassification improvement (NRI) for predicting all-cause death, MI and stroke were estimated to be 6.7% (P<0.001), -1.89% (P=0.029) and -0.20% (P=0.421), respectively. CONCLUSIONS: Better discrimination was achieved using eGFRCKDEPI than eGFRMDRD on univariate analysis. NRI analysis indicated that the use of eGFRCKDEPI instead of eGFRMDRD offered a significant improvement in reclassification of death risk.