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.

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.

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.

Analysis of drug prescription in chronic haemodialysis patients.

BACKGROUND: Information concerning medication use in Asian haemodialysis patients is sparse. We surveyed prescribed medications and examined the relation between the number of medications and mortality and clinical characteristics in chronic haemodialysis patients, in Okinawa, Japan. METHODS: We conducted a cross-sectional multicentre survey in August 1999 and patients were observed during 13 months of follow up. RESULTS: The clinical demographics of 850 chronic haemodialysis patients in seven dialysis units were obtained. Compared with the mean number of medications prescribed in ambulatory patients treated in general practice reported from Ministry of Health and Welfare of Japan (2.7 (n=20 716)), the mean number medications in haemodialysis patients was larger (7.2 (n=850)). The three most prescribed drug types in haemodialysis patients were those related to calcium and phosphate metabolism (88%), antihypertensive agents (71%), and erythropoietin (60%). Among the 850 patients, 38 died during the 13-month follow-up period. The number of medications was positively associated with mortality after adjusting for age, sex, and other clinical factors: the hazard ratio was 1.14 (95% confidence interval 1.03-1.26, P=0.007). A multiple linear regression analysis using the number of medications as a dependent factor and sex and other clinical characteristics as independent factors revealed that male sex (P=0.04), diabetes mellitus (P<0.0001), and duplication of drugs (P<0.0001) were positively correlated with the number of medications. CONCLUSIONS: Multiple drug use was observed in haemodialysis patients. The number of prescribed drugs was a significant predictor of short-term mortality. Male sex, diabetes mellitus, and duplication of drugs were correlated with increases in the number of medications.

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.

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.

End-stage renal disease associated with familial Mediterranean fever.

A 39-year-old man had been suffering from periodic fever since childhood. He was started on hemodialysis due to secondary amyloidosis on December 2000. The patient was believed to have Familial Mediterranean fever (FMF) because of recurrent fever with peritonitis, arthritis and inflammatory changes and secondary amyloidosis in his kidneys, heart and colon. No other family member had recurrent fever. IL-6, TNF, and dopamine beta-hydroxylase were not increased in the febril phase. The patient was homozygous for the M6941 mutation. We report the first Japanese case of FMF associated with amyloidosis and confirmed by a gene mutation.

A patient with adult-onset type II citrullinemia on long-term hemodialysis: reversal of clinical symptoms and brain MRI findings.

A 40-year-old woman was referred for several episodes of coma lasting from 2 hours to 2 days. She had been on maintenance hemodialysis for polycystic kidney disease for 9 months. Laboratory findings showed high serum levels of ammonia and citrulline, and a diagnosis of adult-onset type II citrullinemia was made. Multiple areas of focal brain edema were shown by magnetic resonance imaging. The clinical manifestations of coma and abnormal behavior were resolved with intensified dialysis (ie, four 5-hour sessions per week with glycerol and continuous ambulatory peritoneal dialysis). No abnormal shadow was present on follow-up magnetic resonance imaging. Such intensified dialysis therapy may be effective for adult-onset type II citrullinemia and may be applicable even in patients who do not have end-stage renal disease if liver transplant is not an option.