Masahiko Tozawa

Blood Pressure Predicts Risk of Developing End-Stage Renal Disease in Men and Women

Abstract— 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.

Metabolic Syndrome and Risk of Developing Chronic Kidney Disease in Japanese Adults

Metabolic syndrome is a risk factor for the development of cardiovascular disease. Few prospective studies, however, have examined metabolic syndrome as a risk factor for chronic kidney disease (CKD) in an Asian population. We studied the occurrence of CKD in 6,371 subjects without CKD or diabetes mellitus at baseline 1997 through 2002 in Okinawa, Japan. CKD was defined as dipstick-positive proteinuria (≥1+) or a low estimated glomerular filtration rate (<60 mL/min/1.73 m2). Metabolic syndrome was defined according to the modified criteria of the Adult Treatment Panel III in which body mass index (≥25 kg/m2) was substituted for the waist circumference measurement. Logistic analysis was used to analyze the effect of metabolic syndrome on the development of CKD. During the 5-year follow-up, 369 (5.7%) participants developed CKD. After adjusting for age, sex, current cigarette smoking and alcohol drinking habits at baseline, the relative risk of developing CKD was 1.86 (95% confidence interval: 1.43–2.41, p<0.0001) in subjects with metabolic syndrome. Compared with those without metabolic syndrome risk components, the adjusted relative risk (95% confidence interval) was 1.49 (1.10–2.01), 1.89 (1.38–2.59), and 2.65 (1.19–3.68) in those with 1, 2, or ≥3 metabolic syndrome risk components, respectively. Metabolic syndrome is a significant risk factor for the development of CKD in the Japanese population. Detection and treatment of metabolic syndrome should be stressed as a strategy to prevent CKD.

Multiple risk factor clustering of hypertension in a screened cohort.

Objective A family history of hypertension, obesity, diabetes mellitus, hypercholesterolaemia and hypertriglyceridaemia have all been associated with the risk for hypertension. We evaluated whether the clustering of these risk factors increases the risk for hypertension or whether the accumulation of risk factors is associated with the blood pressure level in non-hypertensive subjects. Methods and subjects We assessed the clinical data and family history of hypertension (in parents and siblings) for 9914 individuals (6163 men and 3751 women, 18–89 years old) who were screened in Okinawa, Japan, in 1997. Results In 9914 subjects (2465 hypertensive and 7449 non-hypertensive subjects), all the five factors were positively associated with hypertension. The odds ratios (95% confidence interval) for the number of risk factors were 1.88 (1.62–2.18) for one risk factor, 3.06 (2.62–3.57) for two, 5.25 (4.37–6.30) for three, 8.71 (6.48–11.72) for four and 24.48 (8.49–70.56) for five, after adjusting for age, sex, alcohol consumption, cigarette smoking and physical exercise habits. In non-hypertensive subjects, multivariate regression analyses showed that the number of risks was positively correlated with blood pressure; the regression coefficient was 1.96 (P < 0.0001) for systolic blood pressure, and 1.47 (P < 0.0001) for diastolic blood pressure after adjusting for age and sex. Conclusions Clustering of risk factors was significantly associated with hypertension. The number of risk factors positively correlated with the blood pressure levels in nonhypertensive subjects. The accumulation of risk factors may play an important role in the pathogenesis of hypertension, and thus the aggregation of risk factors may need to be addressed in primary prevention efforts related to hypertension.

Seasonal Blood Pressure and Body Weight Variation in Patients on Chronic Hemodialysis

Aim: The relation of ambient temperature (AMT) and relative humidity to systolic blood pressure (SBP), diastolic blood pressure (DBP), body weight (BW), and body weight gain between dialysis sessions (ΔBW) was examined in hemodialysis patients by Fourier analysis. Methods and Results: The authors recruited 144 dialysis patients from a hemodialysis center in Okinawa, Japan where there is distinct seasonal variation in monthly AMT but a constant intradiurnal temperature change throughout the year. All patients had been undergoing chronic and regular hemodialysis three times per week. SBP, DBP, and BW before dialysis sessions and ΔBW were recorded in 1994. Mean monthly Okinawa AMT in 1994 was highest in Augsut and lowest in February and March, and the mean monthly relative humidity in 1994 was highest in June and lowest in January. Mean SBP and DBP were lowest in August and June respectively, and greatest in December. BW was lowest in July and September, and greatest in February and March; ΔBW was lowest in July and greatest in January. These seasonal patterns were well reproduced by the first Fourier component. The cross-correlation coefficient showed that monthly mean AMT and SBP, DBP, BW, and ΔBW were correlated with a lag time of 5 or 6 months. The cross correlation coefficient showed that relative humidity and SBP, DBP and ΔBW were also correlated with a 6-month lag time. In analyzing subgroups of patients according to the presence or absence of antihypertensive medications, a seasonal change was observed in the SBP and DBP of patients not being treated with antihypertensives, and in the DBP of patients taking antihypertensive medications, but not in the SBP of patients taking antihypertensive medications. Conclusion: Seasonal variations in SBP, DBP, BW and ΔBW were evident. AMT and the relative humidity correlated strongly with SBP, DBP, BW and ΔBW. The clinical implications of these findings in hemodialysis patients warrant further investigation.

Short-term effects of angiotensin II blockade on renal blood flow and sympathetic activity in awake rats.

To investigate the effects of an angiotensin II type 1 receptor antagonist (CV-11974) on renal blood flow and renal sympathetic nerve activity compared with a calcium antagonist (nicardipine), we measured both parameters in conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to 2 days after surgery, CV-11974 (n = 9) and nicardipine (n = 8) were intravenously administered to decrease arterial pressure in a similar time course and degree of hypotension. CV-11974 increased renal blood flow by 23 +/- 4% at the maximal fall in mean arterial pressure (-32 +/- 1 mm Hg), and renal nerve activity increased by 70 +/- 7%. The maximal increase in renal blood flow (+27 +/- 4%) was observed when mean pressure was reduced by approximately 20 mm Hg. The maximal reduction of renal vascular resistance (-33 +/- 3%) correlated significantly with pretreatment levels of plasma renin concentration (r = -.792). In contrast, nicardipine produced a progressive reduction of renal blood flow and marked increases in heart rate and renal nerve activity. Increases in heart rate and nerve activity were greater than those with CV-11974 treatment (P < .001). At the maximal fall in mean pressure (-32 +/- 1 mm Hg), renal blood flow decreased by 23 +/- 4%, which was significantly correlated with percent changes in renal nerve activity (+150 +/- 11%, r = -.744). Renal denervation in another set of rats (n = 6) improved renal blood flow and renal vascular resistance responses to nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

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

BackgroundDisturbances 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.MethodsWe 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.ResultsTotal 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 ≥ 220 mg/dl or TG ≥ 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.ConclusionsThe present study showed dyslipidemia to be an insignificant predictor of development of ESRD in the general Okinawa population.

Prevalence of hospitalization and prognosis of patients on chronic dialysis

AbstractBackground. The process and mechanisms responsible for the poor survival rate of chronic dialysis patients is not well known, and the prevalence of hospitalization and its prognostic significance in these patients has not been well documented. Methods. We reviewed the database and the clinical records of 2049 patients (1147 men and 902 women) who were on the registries of chronic dialysis programs in Okinawa, Japan. They were prevalent patients on January 1, 1997, and were followed-up for 1 year. Results. Of the 2049 patients, 13% (n = 259; 118 men, 141 women) were hospitalized, with the leading causes of hospitalization being social causes, vascular, infection, and cardiac problems. Among this group of patients, 25% (n = 66; 33 men, 33 women) died during the 12 months of follow-up. In contrast, among those patients not hospitalized, 3% (n = 58; 36 men, 22 women) died. The 1-year survival rate, calculated by the Kaplan-Meier method, was 96% in the nonhospitalized patients; however, it was 75% in those who were hospitalized (P < 0.001). Cox proportional hazard analysis on the risk of death was performed to determine the significance of hospitalization with adjustment for other clinical variables. The adjusted hazard ratio (95% confidence interval) of the presence of hospitalization was 5.48 (3.74–8.01) compared with the absence of hospitalization (P < 0.0001). Conclusions. The prognosis of chronic hemodialysis patients who were hospitalized was poor. Adequate social support, control of hypertension, and improvement of nutritional status may be important factors that decrease the need for hospitalization.

Determinants of prescribed dialysis dose and survival in a cohort of chronic hemodialysis patients.

AbstractBackground. The Determinants of the prescribed dialysis dose have not been well studied in a large patient population. Few studies have examined survival rates after adjusting for dose determinants. Methods. Data were obtained from a cohort of chronic hemodialysis patients for the period January 1991 through December 2000. The prescribed dialysis dose was calculated as the dialyzer membrane area (m2) times session hours, and was expressed as m2h per week. Determinants of the prescribed dialysis dose were examined by multivariate logistic regression analysis of baseline clinical and laboratory variables. Survival curves for each prescribed dose were calculated by the Kaplan-Meier method. Cox proportional hazards analysis was used to evaluate differences in the survival curves after adjusting for confounding variables. The delivered dose of dialysis, Kt/V, was calculated in a subgroup of the cohort. Results. For 1041 patients receiving thrice-weekly dialysis, the mean (SD) dialysis dose was 19.8 (5.8) m2h/week (range, 6.3 to 33.0 m2h/week). The significant and independent determinants of prescribed dialysis dose were sex, age, diabetes mellitus (DM), body mass index (BMI), serum albumin, diastolic blood pressure, serum creatinine, duration of dialysis, and comorbidity. The dialysis dose received by women and patients with DM was relatively low, even when adjusted for BMI (P ≪ 0.01 for both). During the follow-up period, 463 patients died, 60 underwent renal transplant, and 10 were transferred away from Okinawa. The hazard ratio (95% confidence interval) for death was 1.016 (0.995–1.037; not significant) for the dialysis dose (m2h/week) after adjustment for multiple confounding factors. The mean (SD) Kt/V was 1.31 (0.28). The hazard ratio (95% confidence interval) for Kt/V ≧ 1.31 vs Kt/V ≦ 1.30 was 0.706 (0.553–0.900; P = 0.0049). Conclusions. The prescribed dialysis dose did not significantly influence mortality in our cohort. Empirically based prescription practice, such as increasing the prescribed dialysis dose in male patients, when the BMI is large, or when serum creatinine or diastolic blood pressure is high may explain the relatively good prognosis of chronic hemodialysis patients in Japan.

Long-term survival of chronic dialysis patients in comparison to that of stroke and acute myocardial infarction patients

AbstractBackground. There are no data comparing the long-term survival of chronic dialysis patients with that of acute myocardial infarction (AMI) or stroke patients. We obtained outcome data from two community-based registries, one for dialysis patients and one for patients who suffered an AMI or stroke. Methods. Patients were entered into the registries between April 1, 1988, and March 31, 1991, in Okinawa, Japan. Only patients who survived for 28 days after starting dialysis or after the onset of AMI and stroke were studied. A total of 646 chronic dialysis patients, 747 AMI patients, and 3809 stroke patients were followed up until March 1, 1999. Survival rates were compared between the dialysis patients and those suffering AMI or stroke, based on Cox proportional hazard analysis, and relative risk (95% confidence interval [CI]) of death was estimated after adjusting for sex and age at onset. Results. The relative risk (95% CI) of death for AMI and stroke patients was 0.39 (0.33–0.46) and 0.40 (0.36–0.46), respectively, when the death risk of dialysis patients was taken as reference (1.00). The relative risk for patients with cerebral hemorrhage was 0.44 (0.38–0.50), with the value being 0.40 (0.35–0.46) for patients with cerebral infarction, and 0.37 (0.28–0.49) for those with subarachnoid hemorrhage. Conclusions. Survival in dialysis patients is clearly worse than that in AMI and stroke patients. Specific factors leading to the higher mortality rate in dialysis patients remain to be determined.

Improved long-term survival rate of chronic dialysis patients with diabetes mellitus

AbstractBackground. The survival rate of diabetic dialysis patients has been poor. However, it is uncertain whether the survival rate of these patients has been improving. Methods. Using the Okinawa Dialysis Study (OKIDS) registry, in which the records of all chronic dialysis patients in Okinawa, Japan, are filed, we compared the prognosis of dialysis patients with diabetes mellitus (DM) and that of dialysis patients with chronic glomerulonephritis (CGN). Using Cox proportional hazard analysis, we examined the effect of the start year of dialysis on survival after adjusting for confounding variables such as age, sex, and predialysis comorbid conditions. Results. Between 1976 and 1998, a total of 1256 DM patients and 2101 CGN patients started dialysis. In the DM patients who started dialysis between 1976 and 1990, the survival rate was 80.4% at 12 months and 42.1% at 60 months, and among those who started dialysis between 1991 and 1998, the survival rate was 87.9% at 12 months and 55.8% at 60 months. In both disease groups, the relative risk of death was significantly lower in patients who started dialysis between 1991 and 1998 than in those who started dialysis between 1976 and 1990. The adjusted relative risk (95% confidence interval [CI]) was 0.65 (95% CI 0.54–0.77). The relative risk of death of DM to CGN was 2.23 (95% CI, 1.91–2.60) when comparing those treated between 1976 and 1990, and 2.00 (95% CI, 1.62–2.46) when comparing those treated between 1991 and 1998. Conclusions. While the prognosis of diabetic dialysis patients in both categories improved significantly with time, that of DM patients was still worse than that of CGN patients.