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Yoshiharu Ikemiya

Publications and source records attributed to Yoshiharu Ikemiya.

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Relationship between dyslipidemia and the risk of developing end-stage renal disease in a screened cohort.

BACKGROUND: Disturbances in lipid metabolism are often observed in patients with renal failure and could be a risk factor for end-stage renal disease (ESRD). However, few studies have examined abnormal lipid metabolism as a risk factor for the development of ESRD in the general population. METHODS: We examined the cumulative incidence of ESRD based on the results of a community-based mass screening in Okinawa, Japan, which was conducted in 1993 by the Okinawa General Health Maintenance Association. Screenees who developed ESRD by the end of 2000 were identified through the Okinawa Dialysis Study registry. RESULTS: Total cholesterol (TC) data were available for 133,338 (92.6%) of the total 143,948 screenees) and triglyceride (TG) data were available for 132,094 (91.8%). Dyslipidemia was defined as TC > or = 220 mg/dl or TG > or = 150 mg/dl. The cumulative incidences of ESRD, per 1000 screenees, were 1.12 for those without dyslipidemia and 2.53 for those with dyslipidemia. The adjusted hazard ratio (95% confidence interval) for dyslipidemia was 0.856 (0.484-1.516) for men and 1.260 (0.661-2.400) for women; neither was significant when adjustment was made for age, systolic blood pressure, diastolic blood pressure, body mass index, creatinine clearance, diabetes mellitus, and proteinuria. CONCLUSIONS: The present study showed dyslipidemia to be an insignificant predictor of development of ESRD in the general Okinawa population.

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Prevalence of high fasting plasma glucose and risk of developing end-stage renal disease in screened subjects in Okinawa, Japan.

BACKGROUND: The number of diabetic dialysis patients is increasing worldwide. Only a few studies, however, have examined the effect of diabetes mellitus (DM) as a risk factor for the development of end-stage renal disease (ESRD) in the general population. METHODS: We examined the cumulative incidence of ESRD based on the results of community-based mass screening in Okinawa, Japan, performed in 1993 by the Okinawa General Health Maintenance Association. Fasting plasma glucose (FPG) data were available for 78 529 screenees (37 197 men and 41 332 women). DM was diagnosed when the FPG was 126 mg/dl or more. Screenees who developed ESRD by the end of 2000 were identified through the Dialysis Registry, Okinawa Dialysis Study. RESULTS: The mean (SD) FPG was 96.5 (22.8) mg/dl, ranging from 45 to 577 mg/dl. The prevalence of DM among the screenees was 4089 (5.2%). A total of 133 screenees (82 men and 51 women) developed ESRD during the 7.75-year study period. The adjusted odds ratio (95% confidence interval [CI]) in the high-FPG group for the risk of developing ESRD was 3.098 (95% CI, 1.738-5.525; P = 0.0001), when adjusted for age, sex, systolic blood pressure, diastolic blood pressure, body mass index, total cholesterol, triglyceride, hematocrit, serum creatinine, hematuria, and proteinuria. CONCLUSIONS: The results of the present study indicated that FPG is a significant, independent predictor of ESRD. FPG and proteinuria measurements are euqally important in detecting individuals at high risk for developing ESRD.

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Body mass index and the risk of development of end-stage renal disease in a screened cohort.

BACKGROUND: Obesity is associated with proteinuria and could be a risk factor for end-stage renal disease (ESRD). However, few studies have examined the significance of body mass index (BMI) as a risk factor for the development of ESRD in the general population. METHODS: We examined the relationship between BMI and the development of ESRD using data from a 1983 community-based screening in Okinawa, Japan. Screenees who developed ESRD by the end of 2000 were identified through the Okinawa Dialysis Study registry. BMI data were available for 100,753 screenees (47,504 men and 53,249 women) aged >/=20 years. The cumulative incidence of ESRD was analyzed according to the quartile of BMI: <21.0, 21.0 to 23.1, 23.2 to 25.4, and >/=25.5 kg/m(2). RESULTS: The mean (SD) BMI of the screenees was 23.4 (3.3) kg/m(2) (range 7.9 to 59.1 kg/m(2)); the mean was 23.4 kg/m(2) for both men and women. During the follow-up period, 404 screenees (232 men and 172 women) developed ESRD. The cumulative incidences of ESRD per 1000 screenees were, from the lowest to highest BMI quartile, 2.48, 3.79, 3.86, and 5.81. The odds ratio (95% CI) of BMI for developing ESRD, after adjustment for age, sex, systolic blood pressure, and proteinuria, was 1.273 (1.121-1.446, P= 0.0002) for men and 0.950 (0.825-1.094, not significant) for women. CONCLUSION: We found that BMI was associated with an increased risk of the development of ESRD in men in the general population in Okinawa. The maintenance of optimal body weight may reduce the risk of ESRD.

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Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort.

BACKGROUND: Uric acid may be a true mediator of renal disease and progression. However, epidemiological evidence for the significance of serum uric acid levels on the risk for developing end-stage renal disease (ESRD) is scarce in a setting of community-based screening. METHODS: Participants in a 1993 mass screening conducted by the Okinawa General Health Maintenance Association in Okinawa, Japan, were investigated: 48,177 screenees (22,949 men, 25,228 women) older than 20 years for whom serum uric acid data were available were studied. All dialysis patients treated in Okinawa were independently registered in the Okinawa Dialysis Study registry. Participants in the 1993 screening who later entered a dialysis program were identified by using 2 computer registries. The cumulative incidence of ESRD was calculated according to quartiles of baseline serum uric acid levels for each sex. The significance of hyperuricemia (serum uric acid level > or = 7.0 mg/dL [> or =416 micromol/L] in men and > or = 6.0 mg/dL [> or =357 micromol/L] in women) for the risk for developing ESRD was evaluated by means of the Cox model after adjusting for age, blood pressure, body mass index, proteinuria, hematocrit, and total cholesterol, triglyceride, fasting blood glucose, and serum creatinine levels. RESULTS: Mean serum uric acid level was 6.4 +/- 1.4 (SD) mg/dL (381 micromol/L) in men and 4.8 +/- 1.1 mg/dL (286 micromol/L) in women. Prevalences of hyperuricemia were 31.9% in men and 13.6% in women. By the end of 2000, a total of 103 screenees (53 men, 50 women) entered dialysis programs. Calculated incidences of ESRD per 1,000 screenees were 1.22 for men without hyperuricemia and 4.64 for men with hyperuricemia and 0.87 for women without hyperuricemia and 9.03 for women with hyperuricemia. Adjusted hazard ratios for hyperuricemia were 2.004 (95% confidence interval, 0.904 to 4.444; P = not significant) in men and 5.770 (95% confidence interval, 2.309 to 14.421; P = 0.0002) in women. CONCLUSION: Screenees with hyperuricemia were associated with a greater incidence of ESRD. Hyperuricemia (serum uric acid > or = 6.0 mg/dL [> or =357 micromol/L]) was an independent predictor of ESRD in women. Strategies to control serum uric acid levels in the normal range may reduce the population burden of ESRD.

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Blood pressure predicts risk of developing end-stage renal disease in men and women.

Blood pressure as a risk factor for development of end-stage renal disease has not been fully studied, particularly in women. We studied the development of end-stage renal disease from 1983 through 2000 in 98 759 subjects, 46 881 men and 51 878 women, 20 to 98 years of age, who were screened in 1983 in Okinawa, Japan. Data for all dialysis patients registered from 1983 to 2000 in Okinawa were used to identify the screened subjects in whom end-stage renal disease developed. In follow-up, 400 subjects, 231 men and 169 women, had end-stage renal disease. Age, body mass index, and adjusted relative risk for systolic and diastolic blood pressure for both men and women were measured. When these results were compared with an optimal blood pressure, the relative risk of development of end-stage renal disease for those with high-normal blood pressure and hypertension were significant in both men and women. Hypertension is a significant risk factor for development of end-stage renal disease not only in men but also in women. Control of blood pressure within normal levels should be stressed as a strategy to prevent end-stage renal disease in both men and women.

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Proteinuria and the risk of developing end-stage renal disease.

BACKGROUND: Dipstick urinalysis for proteinuria and hematuria has been used to screen renal disease, but evidence of the clinical impact of this test on development of end-stage renal disease (ESRD) is lacking. METHODS: We assessed development of ESRD through 2000 in 106,177 screened patients (50,584 men and 55,593 women), 20 to 98 years old, in Okinawa, Japan, who participated in community-based mass screening between April 1983 and March 1984. We used data from the Okinawa Dialysis Study Registry to identify ESRD patients. Multivariate logistic analyses were performed to calculate adjusted odds ratio and 95% confidence interval (95% CI) for the significance of proteinuria and hematuria on the risk of developing ESRD with confounding variables such as age, gender, blood pressure, and body mass index. A similar analysis was repeated in a subgroup of screened patients in whom serum creatinine data existed. RESULTS: During 17 years of follow-up, 420 screened persons (246 men and 174 women) entered the ESRD program. We identified a strong, graded relationship between ESRD and dipstick urinalysis positive for proteinuria; adjusted odds ratio (95% CI) was 2.71 (2.51 to 2.92, P < 0.001). Similar trends were observed after adding serum creatinine data. Compared with dipstick-negative proteinuria, adjusted odds ratio (95% CI) of proteinuria (1+) was 1.93 (1.53 to 2.41, P < 0.001) in men and 2.42 (1.91 to 3.06, P < 0.001) in women. CONCLUSION: Proteinuria was a strong, independent predictor of ESRD in a mass screening setting. Even a slight increase in proteinuria was an independent risk factor for ESRD. Therefore, asymptomatic proteinuria warrants further work-up and intervention.

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Haematocrit and the risk of developing end-stage renal disease.

BACKGROUND: Anaemia is common in patients with renal failure; however, it is not known whether haematocrit level in the general population is a predictor for developing end-stage renal disease (ESRD). METHODS: A retrospective analysis was conducted to assess the development of ESRD within a population of 71 802 subjects (37 190 men and 34 612 women), 20-99 years, in Okinawa, Japan. Haematocrit data were collected between April 1983 and March 1984 and the subjects were followed forward to the year 2000 whether they were identified in the Okinawa Dialysis Study registry for identification of ESRD. Multivariate logistic analyses were performed to analyse the influence of haematocrit on the development of ESRD after adjusting for age, sex, blood pressure, body mass index, proteinuria and haematuria. In a subgroup of the cohort, similar analyses were repeated adjusting for estimated creatinine clearance by the method of Cockcroft and Gault. RESULTS: The mean (SD) level of haematocrit at the time of screening was 45.3% (3.3%) for men and 38.8% (3.2%) for women. During the 17-year follow-up, 269 patients (171 men and 98 women) were identified with ESRD. The mean time to onset of ESRD was 130.4 (53.6) months. The adjusted odds ratio and 95% confidence interval (CI) for the influence of haematocrit (%) on the development of ESRD was 0.991 and 0.988-0.995 (P<0.0001), suggesting that the lower haematocrit, the greater was the risk of developing ESRD. This finding was repeated in the subgroup analysis that included calculated creatinine clearance (adjusted odds ratio 0.991 and 95% CI 0.984-0.997, P=0.0057). In women, the adjusted odds ratio for haematocrits of 20.0-34.9% was 3.086 (CI 1.770-5.376, P<0.0001) when compared with the reference haematocrits of 35.0-39.9%. In men, the adjusted odds ratio for haematocrits of 25.0-39.9% was 1.927 (CI 1.418-2.625, P<0.0001) when compared with the reference haematocrits of 45.0-49.9%. CONCLUSIONS: Subjects with low haematocrits, <40% for men and <35% for women, have a significantly increased risk of ESRD.

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Estimated protein intake and blood pressure in a screened cohort in Okinawa, Japan.

We examined the relation between protein intake and blood pressure in a screened cohort in Okinawa, Japan. A total of 1,299 screened subjects, 885 men and 414 women, were examined at the Okinawa General Health Maintenance Association. Daily intake of sodium (Na) and potassium (K) was estimated from Na, K, and creatinine excretion by the method of Kawasaki et al., and daily protein intake was estimated by the method of Maroni et al. as the estimated daily urinary excretion of urea nitrogen. Mean (SD) daily protein intake was 71.8 (18.6) g in men and 54.0 (13.5) g in women, and the mean (SD) daily protein intake per unit kg body weight was 1.1 (0.2) g/kg in men and 1.0 (0.2) g/kg in women. In men, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in those with lower protein intake (LP; < 1.0 g/kg/day) than in those with higher protein intake (HP; > or = 1.0 g/kg/day) (p < 0 .05 for DBP). In women, both SBP and DBP were higher in those with LP than in those with HP, but these differences were not statistically significant. However, urinary excretion of both Na and K was lower in those with LP than in those with HP, respectively, both in men and women (p < 0.0001). In summary, estimated daily protein intake was about 1.1 g/kg in men and 1.0 g/kg in women. Despite the higher urinary excretion of Na, both SBP and DBP tended to be lower in those with higher daily protein intake, particularly in men.

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Influence of smoking and obesity on the development of proteinuria.

BACKGROUND: Proteinuria is a significant risk factor for end-stage renal disease. Previous evidence suggested that smoking and obesity increase the risk of proteinuria. However, it is unclear whether these risk factors predict the development of proteinuria independently of hypertension and diabetes mellitus. The aim of this study was to analyze the effects of obesity and smoking on the development of proteinuria in a screened cohort of subjects with normal kidney function. METHODS: A total of 5403 subjects (3403 men and 2000 women) who participated in the 1997 and 1999 health screening examinations in Okinawa Japan, and who were normal renal function (serum creatinine < or =1.2 mg/dL in men, < or =1.0 mg/dL in women) and negative proteinuria by dipstick examination in 1997 were eligible for study. Logistic analysis was used to examine the relation between the baseline state of smoking or obesity in 1997, and the development of proteinuria in 1999, adjusted for age, sex, and other confounding factors. RESULTS: Proteinuria developed in 5.8% of participants (6.7% in men, 4.4% in women; dipstick score, 1+ in 277, 2+ in 37, and > or =3+ in 4 participants). The incidence of proteinuria was positively associated with the number of cigarettes smoked per day (P = 0.04), and a body mass index (P < 0.0001) at baseline. Analysis showed that the relative risk (95% confidence interval) of developing proteinuria was 1.32 (1.00 to 1.74), P = 0.04 for cigarette smoking, 1.45 (1.13 to 1.86), P = 0.002 for obesity, 1.56 (1.19 to 2.06), P = 0.001 for hypertension, and 2.27 (1.55 to 3.32), P < 0.0001 for diabetes mellitus. Stratified with men and women, the relative risk was 1.28 (0.96 to 1.72), P = 0.09 for smoking, and 1.60 (1.19 to 2.14), P = 0.001 for obesity in men; the relative risk was 1.30 (0.44 to 3.80), P = 0.62 for smoking, and 1.04 (0.63 to 1.72), P = 0.87 for obesity in women. CONCLUSIONS: Hypertension and diabetes mellitus were superior to smoking and obesity in predicting the development of proteinuria in all subjects. Stratified with men and women, obesity was a significant risk factor for the development of proteinuria independently of both hypertension and diabetes mellitus in men. The risk of developing proteinuria also tended to be increased with cigarette smoking in men. Smoking and obesity in women were not significant in this data set.

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Triglyceride, but not total cholesterol or low-density lipoprotein cholesterol levels, predict development of proteinuria.

BACKGROUND: Epidemiological data about the relationship between dyslipidemia and proteinuria are sparse. We conducted a retrospective and longitudinal study in a large screened cohort to evaluate whether triglyceride, high-density lipoprotein (HDL) cholesterol, total cholesterol, and low-density lipoprotein (LDL) cholesterol levels increase the risk of development of proteinuria and loss of renal function. METHODS: Post hoc analysis was performed for 4326 subjects who were free from proteinuria (dipstick 1+ or higher) at baseline (1997) with a follow-up period through 2000. Outcome measures were the development of proteinuria (1+ or higher) and change in glomerular filtration rate (GFR). Multiple logistic analysis and multiple regression analysis were used to analyze baseline characteristics related to the outcome measures. RESULTS: During the observational period, 505 (11.7%) of subjects had one or more episodes of proteinuria (>/=1+). Adjusted relative risk of triglycerides for one or more incidences of proteinuria was 1.007 (95% CI 1.000 to 1.105, P = 0.04) in men and 1.032 (95% CI 1.004 to 1.061, P = 0.02) in women. Total cholesterol, HDL cholesterol, and LDL cholesterol were not significant predictors of proteinuria. The mean change in GFR between 1997 and 2000 was -6.3 (SD = 9.0) mL/min/1.73 m2 in men, and -7.8 (SD = 10.7) mL/min/1.73 m2 in women. HDL cholesterol (beta = 0.04, t = 3.7, P = 0.0002) in men and triglycerides (per 10 mg/dL, beta = -0.09, t = -2.2, P = 0.02) in women were correlated with the change in GFR. CONCLUSIONS: High triglyceride levels predicted a risk of developing proteinuria in both men and women, but not total cholesterol nor LDL cholesterol. High triglyceride in women and low HDL cholesterol in men predicted the decline of renal function. It remains to be determined whether prospective treatment of dyslipidemia will protect against renal injury.

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Evidence for elevated pulse pressure in patients on chronic hemodialysis: a case-control study.

BACKGROUND: Few analyses have compared pulse pressure (PP) values in hemodialysis patients with healthy individuals, and they have provided only limited data. We retrospectively examined PP in a large cohort of hemodialysis patients and healthy control subjects. METHODS: The relationships of systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP to mean arterial pressure (MAP) levels were investigated in 234 chronic hemodialysis patients and in 682 control subjects matched for age, sex, diabetes mellitus, and body mass index. RESULTS: In both control and patients, PP was positively correlated with MAP, and the two regression lines were parallel (beta of control subjects = 0.52; beta of hemodialysis patients = 0.57, P = 0.48). According to the regression line, at any MAP level, the PP in hemodialysis patients was significantly higher than that in control subjects: the mean PP difference between control and patients was 19.2 mm Hg (95% CI, 17.2 to 21.1 mm Hg, P < 0.0001). When the relationships between MAP and SBP and that between MAP and DBP were analyzed, the regression lines were also parallel. However, at any MAP level, SBP was higher and DBP was lower in hemodialysis patients than control subjects; the mean SBP difference was 12.8 mm Hg (95% CI, 11.5 to 14.1 mm Hg, P < 0.0001) and mean DBP difference was 6.4 mm Hg (95% CI, 5.7 to 7.0 mm Hg, P < 0.0001). CONCLUSIONS: At any MAP level, hemodialysis patients had a higher SBP, lower DBP, and higher PP values than those control subjects with a normal renal function who were matched for age, sex, diabetes mellitus, and body mass index. Further study is needed to determine whether preventing or reducing an elevated PP improves the prognosis for hemodialysis patients.

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Prevalence and correlates of diabetes mellitus in a screened cohort in Okinawa, Japan.

The incidence of end-stage renal disease due to diabetes mellitus (DM) is increasing. There have been too few epidemiological studies of the predictors of DM nephropathy, particularly type 2 DM, among a statistically significant population. We studied the prevalence and correlates of DM in a screened cohort in Okinawa, Japan. A total of 9,914 screenees (6,163 men and 3,751 women) over 18 years of age underwent a 1-day health check at the Okinawa General Health Maintenance Association between April 1997 and March 1998. Subjects were considered to have DM if they showed a fasting plasma glucose > or = 126 mg/dl and hemoglobin A1c > or = 7.0%, or if they were receiving treatment for DM. Non-DM subjects were followed-up until March 2000 to see whether or not they developed DM. Relative risk for developing DM was evaluated by Cox proportional hazard analysis after adjusting for confounding variables. A total of 673 screenees (520 men and 153 women) were diagnosed with DM. The prevalence of DM was 67.9 per 1,000 screenees (84.4 for men and 40.8 for women). A total of 7,125 non-DM screenees were examined a second time. Among them, 164 screenees (130 men and 34 women) had developed DM during the follow-up period. Over 2 years, the cumulative incidence of DM was 2.3% (2.9% in men and 1.3% in women). The adjusted relative risk (95% confidence interval) for developing DM was highest for proteinuria, or 1.90 (1.14-3.17). The results indicated that the prevalence and incidence of DM were high among this screened cohort in Okinawa, Japan. Subjects with proteinuria may thus be at high risk for developing DM.

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Urinary excretion of sodium and potassium in a screened cohort in Okinawa, Japan.

Information regarding daily intake of sodium (Na) is useful for both normotensive and hypertensive subjects. We measured urinary excretion of sodium (U-Na) and urinary excretion of potassium (U-K) to estimate daily salt intake in a cohort of health screening subjects in Okinawa, Japan. Urine samples were obtained from 2,411 subjects (1,554 men and 857 women) who were examined on a half-day dry-doc at the Okinawa General Health Maintenance Association (OGHMA). Four hundred and one subjects were examined twice, once between September and November in 1997, and once between September and November in 1998. The mean U-Na was 182 mEq/day for men and 176 mEq/day for women. The mean U-K was 54 mEq/day for men and 50 mEq/day for women. U-Na was higher in young men, and U-K was lower in young women. In both men and women, smokers had a significantly lower Na excretion compared to nonsmokers. Subjects treated for hypertension had a significantly lower Na excretion (173 mEq/day) compared to subjects not treated for hypertension (192 mEq/day). Our findings suggest that Na excretion in screened subjects in Okinawa is lower than the national average. Sodium excretion, however, was higher in young men than in elderly subjects, and K excretion was lower in young women than in elderly subjects. Both trends are disadvantageous for controlling hypertension.

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Impact of multiple risk factor clustering on the elevation of blood pressure.

A family history of hypertension, obesity, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia have all been associated with risk of hypertension. We retrospectively conducted a longitudinal study in a large screened cohort to explore the effect of the clustering of these five risk factors on the elevation of blood pressure (BP) in normotensive subjects at baseline. The study group comprised 4,857 normotensive subjects not treated with antihypertensive drugs (systolic BP < 140 mmHg, diastolic BP < 90 mmHg, 3,111 men and 1,746 women) who were followed up from 1997 to 1999. By 1999, 360 subjects had BP at the hypertensive level (systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg). The incidence of subjects whose BP became hypertensive was 37 per 1,000 person-years. After adjusting for age, sex, systolic BP and other clinical factors, multiple logistic analysis showed that the relative risk of BP elevation was 1.49 (95% Cl: 1.09 to 2.05) in subjects with one risk factor; 1.65 (95% Cl: 1.15 to 2.27) in those with two risk factors; 1.42 (95% Cl: 0.91 to 2.32) in those with three; and 4.86 (95% Cl: 2.58 to 9.16) in those with four or more when compared with subjects with no risk factors. Multiple regression analysis showed that the number of risk factors was positively correlated with an increase in BP from 1997 to 1999; the regression coefficient was 0.51 (p = 0.001) for increase in systolic BP, and 0.31 (p = 0.008) for increase in diastolic BP after adjusting for age and sex. In conclusion, clustering of risk factors significantly predicted the development of hypertension.

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