Risk Factors of Preterm Birth in Okinawa Prefecture, the Southernmost Island Prefecture of Japan.

OBJECTIVES: A high rate of preterm birth has been reported in Okinawa Prefecture, the southernmost island prefecture of Japan. Hence, this study aimed to identify the risk factors for preterm birth in this prefecture. METHODS: This retrospective study included data from January 2013 to December 2019 from three facilities in Okinawa Prefecture. Of 13,468 cases of preterm birth at ≥ 22 weeks of gestation, 11,868 were included in this study. Stillbirth and multiparity cases were excluded. First, we compared the overall preterm and full-term birth groups by categorizing the patient background, obstetric, and fetal risk factors. Further, we categorized preterm births into three groups (22-27, 28-33, and 34-36 weeks of gestation) and examined patient background factors to identify potential risk factors for the occurrence of preterm birth in each group. RESULTS: Preterm births accounted for 21.2% (2,521 cases) of all cases, with the rates of 2.6% (317 cases), 6.7% (800 cases), and 11.8% (1,404 cases) at 22-27, 28-33, and 34-36 weeks of gestation, respectively. To prevent preterm birth in Okinawa Prefecture, the present study specifically focused on patient background characteristics. In the multinomial logistic regression, the risk factors for preterm birth at 22-27 weeks of gestation were previous preterm birth (P < 0.0001) and lower age (P = 0.026); at 28-33 weeks of gestation, the risk factors were previous preterm birth (P < 0.0001) and history of cervical conization (P = 0.009); and at 34-36 weeks of gestation, only previous preterm birth (P < 0.0001) was a risk factor. CONCLUSIONS FOR PRACTICE: Previous preterm birth, younger age, and history of cervical conization were risk factors for Preterm birth in Okinawa. To reduce premature births in Okinawa Prefecture, it is important to pick up women with these risk factors and provide them with appropriate guidance and education on an ongoing basis.

Cost-effectiveness of mass screening for dipstick hematuria in Japan.

BACKGROUND: Dipstick urine tests are a simple and inexpensive method for detecting kidney and urological diseases, such as IgA nephropathy and bladder cancer. The nationwide mass screening program, Specific Health Checkup (SHC), started in Japan in 2008 and targeted all adults between 40 and 74 years of age. Dipstick urine tests for proteinuria and glucosuria are mandatory as part of the SHC, but dipstick urine tests for hematuria are not. However, the dipstick hematuria test is often administered simultaneously with these mandatory tests by some health insurers. Hematuria is common in Japanese general screening participants, particularly elderly women, and the necessity of mass screening using the dipstick hematuria test has been discussed. This study aimed to evaluate the cost-effectiveness of mass screening for dipstick hematuria tests in addition to the SHC. METHODS: Using a decision tree and Markov modeling, we conducted a cost-effectiveness analysis from a Japanese societal perspective. RESULTS: Compared with the current SHC, mass screening for dipstick hematuria tests, in addition to the SHC, costs less and gains more, which means cost-saving. Similar findings were observed in the sex-specific analysis. CONCLUSION: Our results suggest that mandating the dipstick hematuria test could be justifiable as an efficient use of finite healthcare resources. The results have implications for mass screening programs not only in Japan but worldwide.

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

BACKGROUND: A recent cost-effectiveness analysis (CEA) study evaluated the widespread diffusion of behaviour modification intervention for patients with chronic kidney disease (CKD). Incorporating this behaviour modification intervention, comprising educational sessions on nutrition/lifestyle and support for regular patient visits, to the current CKD guideline-based practice was found to be cost-effective. This study aimed to examine the affordability of this efficient new practice under the hypothesis that the behaviour modification intervention would be initiated by general physicians (GPs). METHODS: A budget impact analysis was conducted by defining the target population as patients aged 40-74 years with stage-3-5 CKD based on the prevalence of definitive CKD in the Japanese general population. Costs expended by social insurers without discount were counted as budgets. We estimated the annual budget impact for 15 years by running our CEA model, assuming that it would be good for the span. RESULTS: We estimated the number of patients with end-stage kidney disease (ESKD) to decrease by 4,496 in the fifteenth year of the new practice using our CEA model. Compared to that in the current practice, the budget impact as total additional expenditure of the new practice was estimated to be negative by the tenth year in the base case. CONCLUSIONS: The widespread diffusion of behaviour modification intervention would contain public health care expenditure over the mid-to-long term, resulting from a reduction in progression to ESKD. We suggest that providing sufficient economic incentives to GPs and strengthening recommendations in CKD guidelines would realise effective GP-initiated interventions.

Comparison of annual eGFR decline among primary kidney diseases in patients with CKD G3b-5: results from a REACH-J CKD cohort study.

BACKGROUND: Disease-specific trajectories of renal function in advanced chronic kidney disease (CKD) are not well defined. Here, we compared these trajectories in the estimated glomerular filtration rate (eGFR) by CKD stages. METHODS: Patients with multiple eGFR measurements during the 5-year preregistration period of the REACH-J study were enrolled. Mean annual eGFR declines were calculated from linear mixed effect models with the adjustment variables of baseline CKD stage, age, sex and the current CKD stage and the level of proteinuria (CKDA1-3). RESULTS: Among 1,969 eligible patients with CKDG3b-5, the adjusted eGFR decline (ml/min/1.73 m2/year) was significantly faster in diabetic kidney disease (DKD) patients and polycystic kidney disease (PKD) patients than in patients with other kidney diseases (DKD, - 2.96 ± 0.13; PKD, - 2.82 ± 0.17; and others, - 1.95 ± 0.05, p < 0.01). The declines were faster with higher CKD stages. In DKD patients, the eGFR decline was significantly faster in CKDG5 than CKDG4 (- 4.10 ± 0.18 vs - 2.76 ± 0.20, p < 0.01), while these declines in PKD patients were similar. The eGFR declines in PKD patients were significantly faster than DKD patients in CKDG4 (- 2.92 ± 0.23 vs - 2.76 ± 0.20, p < 0.01) and in CKDA2 (- 3.36 ± 0.35 vs - 1.40 ± 0.26, p < 0.01). CONCLUSION: Our study revealed the disease-specific annual eGFR declines by CKD stages and the level of proteinuria. Comparing to the other kidney diseases, the declines in PKD patients were getting faster from early stages of CKD. These results suggest the importance of CKD managements in PKD patients from the early stages.

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

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

Longitudinal change in blood pressure and risk of end-stage renal disease in a community-based cohort in Okinawa.

BACKGROUND: The appropriate blood pressure target to prevent end-stage renal disease (ESRD) is controversial. METHODS: We examined the association between systolic blood pressure (SBP) changes and ESRD incidence in 69,575 participants from the Okinawa general population aged ≥ 20 years who underwent health check-ups in 1993 and more than once in 1994-1996. ESRD incidence was identified using dialysis registry until 2011. Cox proportional hazards model was used to estimate hazard ratio (95% confidence interval) with confounding factor adjustment. RESULTS: At baseline, 29.9%, 22.1%, 20.6%, and 27.5% of subjects had SBP < 120, 120-129, 130-139, and ≥ 140 mmHg, respectively. Only 405 subjects developed ESRD. After 1 year, SBP was lowered, unchanged, and elevated in 20.8%, 54.3%, and 24.9% of subjects, respectively. Compared to the subjects with SBP < 120 mmHg both at baseline and the second measurement, there was no significant risk of ESRD in those who had SBP < 130 mmHg both at baseline and 1-3 years and or those with baseline SBP 130-139 mmHg and 1- to 3-year SBP < 140 mmHg. Subjects with baseline SBP 120-129 mmHg and 1- and 2-year SBP ≥ 130 mmHg were not significant (1.51 [0.86-2.66] and 1.73 [0.95-3.15], respectively) but 3-year SBP ≥ 130 mmHg had a significant ESRD risk (2.37 [1.23-4.56]). Subjects with baseline SBP ≥ 130 mmHg and 1- to 3-year SBP ≥ 140 mmHg had significant ESRD risk. CONCLUSION: Subjects with SBP < 130 mmHg at baseline and 1-3 years showed no significant risk of developing ESRD, in the general population.

Association of dipstick hematuria with all-cause mortality in the general population: results from the specific health check and guidance program in Japan.

Background: Dipstick urine tests are used for general health screening in Japan. The effects of this screening on mortality have not been examined, especially with regard to hematuria. Methods: Subjects were those who participated in the 2008 Tokutei-Kenshin (nationwide specific health check and guidance program) in six districts in Japan. Using the national database of death certificates from 2008 to 2012, we identified subjects who might have died. We verified the candidates in collaboration with the regional National Health Insurance agency and public health nurses. Data were released to the research team supported by the Ministry of Health, Labor, and Welfare of Japan. Dipstick results of 1+ and higher were defined as hematuria (+). Hazard ratio (HR) [95% confidence interval (CI)] was calculated using the Cox proportional hazard analysis. Results: Among 112 115 subjects, we identified that 1290 had died by the end of 2012. In hematuria (-) subjects, the crude mortality rates were 1.2% (1.8% in men, 0.7% in women), whereas in hematuria (+) subjects, they were 1.1% (2.9% in men, 0.7% in women). After adjusting for age, body mass index, estimated glomerular filtration rate, proteinuria, comorbid condition (diabetes mellitus, hypertension and dyslipidemia), past history (stroke, heart disease and kidney disease) and lifestyle (smoking, drinking, walking and exercise), the HR (95% CI) for dipstick hematuria (+) in men was 1.464 (1.147-1.846; P = 0.003), whereas that for hematuria (-) was 0.820 (0.617-1.073; P = 0.151). Conclusions: Dipstick hematuria is significantly associated with mortality in men among Japanese community-based screening participants.

Importance of glomerular filtration rate change as surrogate endpoint for the future incidence of end-stage renal disease in general Japanese population: community-based cohort study.

BACKGROUND: Because of the necessity for extended period and large costs until the event occurs, surrogate endpoints are indispensable for implementation of clinical studies to improve chronic kidney disease (CKD) patients' prognosis. METHODS: Subjects with serum creatinine level for a baseline period over 1-3 years were enrolled (n = 69,238) in this community-based prospective cohort study in Okinawa, Japan, and followed up for 15 years. The endpoint was end-stage renal disease (ESRD). The percent of estimated glomerular filtration rate (%eGFR) change was calculated on the basis of the baseline period. RESULTS: Subjects had a mean ± SD age, 55.59 ± 14.69 years; eGFR, 80.15 ± 21.15 ml/min/1.73 m2. Among the subjects recruited, 15.81% had a low eGFR (<60 ml/min/1.73 m2) and 36.1/100,000 person years developed ESRD. Cox proportional hazards models adjusted for baseline characteristics showed that the risk of ESRD tended to be high with high rates of decrease in %eGFR changes over 2 or 3 years in the high- and low-eGFR groups. The specificities and positive predictive values for ESRD based on a cutoff value of %eGFR change of less than -30% over 2 or 3 years were high in the high- and low-eGFR groups. CONCLUSIONS: %eGFR change tends to be associated with the risk of ESRD. %eGFR change of less than -30% over 2 or 3 years can be a candidate surrogate endpoint for ESRD in the general Japanese population.

Glucosuria and all-cause mortality among general screening participants.

BACKGROUND: Dipstick urine tests are used for general health screening in Japan, but how the test results (e.g., glucosuria) relate to mortality is unknown. METHODS: Subjects participated in a nationwide screening in 2008 in six districts in Japan. We identified those who might have died using the national database of death certificates from 2008 to 2012 (total registered ~ 6 million) and verified candidates with the regional National Health Insurance Agency and public health nurses. Diabetes mellitus (DM) was defined as HbA1c ≥ 6.5%, fasting blood glucose ≥ 126 mg/dl, or medicated for DM. Hazard ratio (HR) and 95% confidence interval (CI) were calculated by Cox proportional hazard analysis. Glucosuria was defined as dipstick ≥ 1 +. RESULTS: Among 209,060 subjects, we identified 2714 fatalities (median follow-up 3.57 years). Crude mortality rates were 1.2% for those without glucosuria and 3.4% for those with glucosuria. After adjusting for sex, age, body mass index, comorbidity (DM, hypertension, and dyslipidemia), history (stroke, heart disease, and kidney disease), and lifestyle (smoking, drinking, walking, and exercise), the HR (95% CI) for dipstick glucosuria was 1.475 (1.166-1.849, P < 0.001). DM subjects with glucosuria (N = 4655) had a higher HR [1.302 (1.044-1.613, P = 0.020)] than DM subjects without glucosuria (N = 20,245), and non-DM subjects with glucosuria (N = 470) had a higher HR [2.511 (1.539-3.833, P < 0.001)] than non-DM subjects without glucosuria (N = 183,690). CONCLUSION: Dipstick glucosuria significantly affected mortality in Japanese community-based screening participants.

Dipstick proteinuria and all-cause mortality among the general population.

BACKGROUND: Dipstick proteinuria, but not albuminuria, is used for general health screening in Japan. How the results of dipstick proteinuria tests correlate with mortality and, however, is not known. METHODS: Subjects were participants of the 2008 Tokutei-Kenshin (Specific Health Check and Guidance program) in six districts in Japan. On the basis of the national database of death certificates from 2008 to 2012, we used a personal identifier in two computer registries to identify participants who might have died. The hazard ratio (95% confidence interval, CI) was calculated by Cox-proportional hazard analysis. RESULTS: Among a total of 140,761 subjects, we identified 1641 mortalities that occurred by the end of 2012. The crude mortality rates were 1.1% for subjects who were proteinuria (-), 1.5% for those with proteinuria (+/-), 2.0% for those with proteinuria (1+), 3.5% for those with proteinuria (2+), and 3.7% for those with proteinuria (≥ 3+). After adjusting for sex, age, body mass index, estimated glomerular filtration rate, comorbid condition, past history, and lifestyle, the hazard ratio (95% CI) for dipstick proteinuria was 1.262 (1.079-1.467) for those with proteinuria (+/-), 1.437 (1.168-1.748) for those with proteinuria (1+), 2.201 (1.688-2.867) for those with proteinuria (2+), and 2.222 (1.418-3.301) for those with proteinuria (≥ 3+) compared with the reference of proteinuria (-). CONCLUSION: Dipstick proteinuria is an independent predictor of death among Japanese community-based screening participants.

A nationwide prospective cohort study of patients with advanced chronic kidney disease in Japan: The Reach-J CKD cohort study.

BACKGROUND: Epidemiology and outcomes of Japanese patients with advanced chronic kidney disease (CKD)-an estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m2-has remained largely unexamined. METHODS: We conducted a nationwide survey to determine the distribution of Japanese CKD patients, and are conducting a cohort study of these patients. A questionnaire eliciting details about facilities and their CKD practices was sent to all clinics/hospitals with nephrologists. Based on the survey results, we recruited 2400 advanced CKD patients receiving nephrologist care from at least 30 representative facilities throughout Japan, selected randomly with stratification by region and facility size. Through patient questionnaires and nephrologist-practice surveys aligned with the international CKD Outcomes and Practice Patterns Study (CKDopps), we shall annually or semi-annually collect patient, physician and clinic data prospectively, detailing CKD practices for 5 years, with a primary outcome of death or renal replacement therapy initiation, and secondary outcomes being decline of eGFR by 30% or 50%, CKD progression to CKD G5, or a cardiovascular event. RESULTS: Of 790 eligible, responding facilities, 330 (41.8%) treat ≥80 advanced CKD patients in the average 3-month period. Regional distribution of these facilities is similar to that of persons in the general population. Hence, the 30 facilities selected for data collection appear to be geographically representative in Japan. CONCLUSIONS: Our study will enhance understanding of various CKD practices and biological data associated with CKD progression, and allow international comparisons using the CKDopps platform. This will provide evidences to improve the health and quality of life for patients with advanced CKD.

Observation period for changes in proteinuria and risk prediction of end-stage renal disease in general population.

AIM: Proteinuria is known to be an independent risk factor of end-stage renal disease (ESRD). But the associations between changes in dipstick proteinuria and the risk of ESRD in the general population and its appropriate observation period to predict incident ESRD are unknown. METHODS: We assessed the changes in dipstick proteinuria in 69 021 participants aged ≥20 years who participated in health check-ups from 1993 and more than once until 1996 in Okinawa, Japan. Development of ESRD until 2011 was identified using dialysis registry. Cox proportional hazards model and receiver operating characteristic (ROC) curve were used. RESULTS: At baseline, proteinuria (±) and ≥(1+) were observed in 2.4% and 1.2% of total subjects. 1.5% of subjects had decreased and 9.4% of subjects had increased their proteinuria level after 2 years. After adjustment for confounding factors, hazard ratios (95% confidence interval) of ESRD for subjects with proteinuria change ≤ - 1, +1, +2, +3, and +4 level during 2 years compared to subjects with no change were 0.89 (0.43-1.87), 3.18 (2.21-4.60), 8.01 (5.55-11.55), 11.17 (6.59-19.95), and 16.59 (5.95-46.25), respectively. Heterogeneity existed between changes in proteinuria level during 1 or 3 years and the risk of ESRD among baseline proteinuria. Area under the ROC curve (95%CI) to predict ESRD by increase in proteinuria level during 1, 2, and 3 years were 0.650 (0.623-0.679), 0.779 (0.751-0.808), and 0.778 (0.748-0.808), respectively. CONCLUSIONS: The changes in dipstick proteinuria were an independent predictor of ESRD in the general population. Changes in proteinuria over 2 years may be appropriate for the risk prediction of ESRD.

Mortality risk among screened subjects of the specific health check and guidance program in Japan 2008-2012.

BACKGROUND: In Japan, the Specific Health Check and Guidance (Tokutei-Kenshin) has started in 2008. However, the relationship between the baseline characteristics and mortality has not been examined. METHODS: Subjects were those who participated at the 2008 Tokutei-Kenshin in six districts with baseline data of serum creatinine. Using National database of death certificate from 2008 to 2012, we identified those who might have died and confirmed further with the collaborations of the regional National Health Insurance agency and public health nurses. The data was released to the research team supported by the Ministry of Health, Labor, and Welfare of Japan, and is governed by strict regulation and is completely encrypted with the individual's name and residence. Causes of death were classified by ICD-10. RESULTS: Among the total of 295,297 subjects, we identified 3764 fatal cases by end of 2012. The median BMI was 23.8 kg/m2 in men and 22.5 kg/m2 in women, respectively. Proteinuria, dipstick 1+ and over, was positive in 5.3%. The median eGFR was 73.8 ml/min/1.73 m2 among those with data available in 81% of the total cohort (N = 239,274). The leading cause of death was neoplasm in both genders. It was 51.6% of the total, 50.4% in men and 53.7% in women. The second cause of death was circulatory; 20.4% of the total, 21.1% in men and 19.2% in women. CONCLUSION: Half of the causes of death was related to neoplasm among the cohort of the Tokutei-Kenshin. Effects of baseline demographics such as lifestyle and CKD remained to be studied.

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.

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.

Underestimating chronic kidney disease by urine dipstick without serum creatinine as a screening tool in the general Japanese population.

BACKGROUND: It is not known if urine dipstick alone can identify chronic kidney disease (CKD) in the general Japanese population. METHODS: We designed a cross-sectional study using data obtained in 2008 from a nationwide community-based health examination program for adults aged 40-74. The data consisted of blood tests, urine tests and questionnaire related to metabolic disorders. Those who had both serum creatinine measured and urine dipstick tested were analyzed. RESULTS: Data were obtained from 538,846 people with a mean age of 62.8 years, consisting of 41.6 % males. Our study showed that 14.4 % had an eGFR below 60 mL/min/1.73 m(2), 5.2 % had proteinuria and 18.1 % had CKD. Within the population with CKD, non-proteinuric CKD accounted for 71.4 %. The proportion of non-proteinuric CKD was highest in stage G3a (91.8 %) followed by G3b (77.0 %) disease, and was greater in the more elderly and in females. The proportion of non-proteinuric CKD was 47.9 % in diabetes mellitus, 69.3 % in dyslipidemia, 66.8 % in hypertension and 57.1 % in metabolic syndrome. Furthermore, non-proteinuric CKD accounted for 78.1 % of the population without these lifestyle diseases, suggesting that even in the population without apparent risk, CKD is still prevalent and can be missed when urine dipstick is the only screening method used. CONCLUSIONS: This study showed that a considerable population of CKD might be overlooked when only dipstick proteinuria is assessed for CKD screening. Hence, we strongly recommend that both urinalysis and serum creatinine measurement should be a part of the nationwide CKD screening system.

Effect of glomerular filtration rate and proteinuria on medical cost among screened subjects.

BACKGROUND: Chronic kidney disease is a predictor of end-stage renal disease (ESRD) and cardiovascular disease (CVD). Therefore, the medical expenses are higher with the decrease in glomerular filtration rate (GFR). However, few studies have examined the medical expenses according to the baseline GFR. METHODS: We investigated the relationship between GFR at health checks and medical expenses, combining the registries of both the health checks and report of medical expenses (receipts). The health checks were done from April 2008 to March 2009, and the eligible subjects were covered by the Okinawa Branch of the Japan Health Insurance Association. All reports of medical expenses were reviewed from April 2008 to March 2010 (24 months). RESULTS: A total of 74,354 subjects, 38.2 % females with the mean age of 48.1 years, were examined according to whether they had visited medical facilities during the study period. The total number of receipts was 773,276. The average receipt point, 1 point = 10 Yen, was 686,410 (eGFR < 15), 56,408 (eGFR 15-29), 47,263 (eGFR 30-44), 24,372 (45-59), 16,018 (eGFR 60-74), 13,893 (eGFR 75-89), 13,990 (eGFR 90-104), 14,717 (eGFR 105-119), and 19,139 (eGFR 120 and over), respectively. The relationship between eGFR and medical expense was U-shaped, and the expense was lowest at eGFR 75-89. CONCLUSION: We demonstrate that the medical expenses increase as eGFR decreases. Subjects with higher eGFR, 120 and over, seemed to have higher medical expenses.

Elevated resting heart rate is an independent predictor of all-cause death and cardiovascular events in Japanese ambulatory hemodialysis patients.

BACKGROUND: Elevated heart rate (HR) is an independent risk factor for all-cause death or cardiovascular events in non-hemodialysis subjects; however, the clinical significance of elevated HR in hemodialysis patients is not well studied. METHODS: We prospectively evaluated the relationship between HR and adverse outcome in a total of 229 ambulatory hemodialysis patients (57 % men; mean age 62.2 years) recruited from two dialysis clinics in 2009. Mean (SD) HR of this cohort was 74.1 (11.0) beats per minute (bpm). RESULTS: Receiver operating characteristic curves identified an HR cut-off level of ≥80 bpm for increased adverse outcome. After a mean follow-up of 525 days (range 7-760 days) a total of 30 primary endpoints (21 all-cause deaths, 4 acute coronary syndromes and 8 strokes) and 38 secondary endpoints (30 primary endpoints, 8 congestive heart failures, and 5 other cardiovascular events) were detected. Cox regression analysis revealed that HR >80 bpm was not an independent predictor of primary endpoints [hazard ratio 1.81, 95 % confidence interval (CI) 0.79-4.11, p = NS], but of secondary endpoints (hazard ratio 2.01, 95 % CI 1.01-4.22, p < 0.05) after adjusting for age, sex, hemodialysis duration, and cardiovascular risks. CONCLUSIONS: Elevated HR is an independent predictor of all-cause death and cardiovascular events in Japanese ambulatory hemodialysis patients.

C-reactive protein is a predictor for developing proteinuria in a screened cohort.

BACKGROUND: The relationship between C-reactive protein (CRP) and proteinuria is not known. METHODS: We examined 20,077 screenees (men: 52.4%) of the Okinawa General Health Maintenance Association (OGHMA) registry who were examined between 2004 and 2006. Cross-sectional and longitudinal relationships between CRP and dipstick proteinuria were examined. The OGHMA central laboratory measured creatinine and CRP levels using an autoanalyzer (normal: <0.30 mg/dl). The glomerular filtration rate was estimated using the Japanese formula. RESULTS: The prevalence of dipstick-positive proteinuria increased from 5.2% in screenees with a low CRP level of <0.10 mg/dl to 12.3% in those with high CRP levels (0.30-0.90 mg/dl). The CRP values did not affect the mean (SD) estimated glomerular filtration rate: 76.9 (13.7) with low CRP and 76.4 (15.1) with high CRP levels. We examined the relationship between baseline CRP and the development of proteinuria among subjects screened in 2004. Of 8,315 subjects without proteinuria examined again by 2006, 370 (4.4%) had developed proteinuria. The odds ratio (95% CI) for high CRP levels (0.30-0.90 mg/dl; reference CRP: <0.10 mg/dl) was 1.433 (1.013-2.028; p = 0.0422) after adjusting for multivariate variables, suggesting that CRP is closely associated with the prevalence and incidence of proteinuria. CONCLUSION: A prospective study on the development of proteinuria among those with high CRP levels is warranted. Screenees with high CRP levels may need to be followed up carefully despite the absence of traditional risk factors for proteinuria.