Kiyoyuki Tokuyama

Impact of the initial levels of laboratory variables on survival in chronic dialysis patients

Besides the age at start of dialysis and the presence of diabetes mellitus, serum albumin has been shown to be a significant predictor of survival in prevalent dialysis patients. However, this was not evaluated in incipient dialysis patients. The initial biochemical variables were retrieved for a large dialysis population (N = 1,982) who were started on chronic dialysis in Okinawa, Japan from 1971 to 1990. Biochemical data that included blood urea nitrogen, serum creatinine, serum electrolytes (sodium, potassium, calcium, and phosphate), total cholesterol, triglyceride, total protein, serum albumin, and hematocrit obtained just before the first dialysis session were available for 1,491 (75.2%) patients. Six hundred sixty-four (43.2%) patients died by the end of 1993. Cox proportional analysis adjusted for sex, age, year of start of dialysis, presence of diabetes mellitus, and the laboratory variables was performed to examine the significance of the initial biochemical data on survival. The risk ratio was 0.577 (P = 0.0025) in serum albumin, 1.291 (P = 0.0138) in serum potassium, and 0.966 (P = 0.0202) in serum sodium. The study results support the notion that nutritional status is important for survival in chronic dialysis patients. Causes of hypoalbuminemia, hyperkalemia, and hyponatremia should be evaluated carefully at initiation of dialysis.

Effects of angiotensin receptor blockade (ARB) on mortality and cardiovascular outcomes in patients with long-term haemodialysis: a randomized controlled trial

BACKGROUND Hypertension is a major risk factor for death and cardiovascular disease (CVD) in patients undergoing chronic haemodialysis (HD), but there is uncertainty surrounding the effects of blood pressure (BP) lowering on this high-risk patient group. METHODS In a multicenter, prospective, randomized, open-label, blinded-endpoint trial, 469 patients with chronic HD and elevated BP (140-199/90-99 mmHg) were assigned to receive the angiotensin receptor blockade (ARB) olmesartan (at a dose of 10-40 mg daily; n = 235) or another treatment that does not include angiotensin receptor blockers and angiotensin-converting enzyme (ACE) inhibitors (n = 234). The primary outcomes were the following: (i) composite of death, nonfatal stroke, nonfatal myocardial infarction and coronary revascularization and (ii) all-cause death. RESULTS During a mean follow-up of 3.5 years, the mean BP was 0.9/0.0 mmHg lower in the olmesartan group than in the control group (not significant). A total of 68 patients (28.9%) in the olmesartan group and 67 patients (28.6%) in the control group had subsequent primary composite endpoints [hazard ratio (HR) in the olmesartan group 1.00, 95% confidence interval (CI) 0.71-1.40, P = 0.99]. All-cause deaths occurred in 38 patients (16.2%) in the olmesartan group and 39 (16.7%) in the control group (HR, 0.97; 95% CI, 0.62-1.52, P = 0.91). Olmesartan did not alter the risks of serious adverse events. CONCLUSIONS BP-lowering treatment with an ARB did not significantly lower the risks of major cardiovascular events or death among patients with hypertension on chronic HD. (Cochrane Renal Group Prospective Trial Register number CRG010600030).

Increased Risk of Cardiovascular Disease with Erythropoietin in Chronic Dialysis Patients

Recombinant human erythropoietin is widely used in chronic dialysis patients. However, the long-term effect, especially on the incidence of cardiovascular disease, has not been critically evaluated. We observed the annual incidence of stroke and acute myocardial infarction from April 1988 through March 1993 in Okinawa, Japan. Until April 1990, erythropoietin was not generally used. Therefore, we have two periods: pre-erythropoietin, April 1988 through March 1990, and post-erythropoietin, April 1990 through March 1993. Two thousand one hundred and sixteen patients (1,219 males and 897 females) were on chronic dialysis during the study period by March 31, 1993. Every case of stroke and acute myocardial infarction during the study period was registered. The odds ratio was calculated using the data of the general population in each sex and age class obtained in the same area. A total of 86 cases of stroke and 15 cases of acute myocardial infarction were registered during the study period. The annual incidence, per 1,000 patient-years, of stroke was 12.5 (1988), 10.5 (1989), 12.7 (1990), 14.0 (1991), and 17.5 (1992). The incidence of stroke was increased in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.22 and 95% confidence interval (95% CI 1.06-1.41, p < 0.01). The annual incidence of acute myocardial infarction was 1.0 (1988), 1.8 (1989), 0.8 (1990), 2.9 (1991) and 4.7 (1992). The incidence of acute myocardial infarction was increased significantly in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.87 (95% CI 1.66-2.10, p < 0.01). The odds ratio of stroke to the general population was 4.25 (95% CI 3.10-5.82) in the pre-erythropoietin and 4.58 (95% CI 2.14-9.80) in the post-erythropoietin period. In acute myocardial infarction, it was 2.98 (95% CI 2.84-3.12) and 3.81 (95% CI 3.18-4.56). The odds ratio of acute myocardial infarction was significantly increased (p < 0.01). The introduction of erythropoietin was associated with an increased risk of cardiovascular disease, especially acute myocardial infarction. Erythropoietin may unmask the sclerotic lesion in chronic dialysis patients.

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.