Hajime Uehara

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.

Epidemiologic Analysis of Diabetic Patients on Chronic Dialysis

We retrospectively surveyed all of the available medical records of 404 (191 females and 213 males) chronic dialysis patients, of whom 16 (4%) had insulin-dependent diabetes mellitus (IDDM) and 388 (96%) non-insulin-dependent diabetes mellitus (NIDDM). The patients were among 2,214 dialysis patients in Okinawa, Japan, of whom 443 were diabetic. The patients entered a large population-based dialysis registry. The mean duration from the diagnosis of diabetes mellitus (DM) to dialysis was 181.6 months in the IDDM patients and 150.4 months in the NIDDM patients. The NIDDM patients were classified into four subgroups according to their status when DM was first suspected. The duration from the diagnosis of DM until the onset of dialysis treatment was significantly shorter than in any other subgroup or in the IDDM subgroup with major vascular disease (131.9 months). Otherwise, the course of renal disease in NIDDM patients was similar to that in IDDM individuals. Most of our dialysis patients with DM had NIDDM. In most of the NIDDM patients, the diagnosis had been delayed for several years for unknown reason. However, if diagnosed early, NIDDM shows a clinical time course until dialysis similar to that of IDDM. Whether NIDDM patients contract chronic renal disease at an equal incidence to that of IDDM patients and the fraction of all diabetic patients accepted for chronic dialysis remain to be determined.

Effect of renal diseases and comorbid conditions on survival in chronic dialysis patients

International and geographical differences in the survival rates of chronic dialysis patients can be explained by differences in primary renal disease, in the acceptance rate of elderly patients, and in predialysis comorbid conditions. Several studies have shown the effects of these factors on survival. However, in most studies, a large number of patients may leave for renal transplantation or transfer to other centers, so that precise analysis becomes impossible. Although the number of patients in our registry is not so large (n = 1,982), we have few such problems and were able to examine the effects of the above-mentioned factors on patient survival using the Cox proportional hazard model. Hazard ratios (HR) and 95% confidence intervals were 0.739 and 0.366-1.491 in patients with polycystic kidney disease (n = 38), 2.669 and 1.513-4.708 in patients with systemic lupus erythematosus (n = 39), 1.245 and 0.935-1.660 in patients with nephrosclerosis (n = 122), 1.815 and 1.447-2.229 in patients with diabetes mellitus (n = 374), and 1.595 and 1.201-2.117, respectively, in patients with other renal diseases (n = 146) when the HR in patients with chronic glomerulonephritis (n = 1,263) was taken as 1.00. HR and 95% confidence intervals were 1.222 and 1.016-1.470 in patients with one comorbid condition (n = 217) and 1.494 and 1.033-2.160, respectively, in patients with two comorbid conditions (n = 24) when the HR of patients with no predialysis comorbid conditions (n = 1,741) was taken as 1.00. Our data demonstrate the effects of renal diseases and number of predialysis comorbid conditions on the survival in chronic dialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of ATLV and HIV among Hemodialysis Patients in Japan

Human immunodeficiency virus (HIV) and adult T cell leukemia virus (ATLV) can both be transmitted through blood transfusions and blood products. HIV infections are up to the present time uncommon in Japan while the southwestern area of Japan is endemic for ATLV. This study examines the prevalence of HIV and ATLV among Japanese hemodialysis patients who may be at increased risk of viral exposure because they sometimes receive multiple blood transfusions. 1066 patients were examined including 66 from Okinawa--a highly endemic area for ATLV. 7 of the 1066 patients tested positive for HIV using an enzyme immunoassay but none were confirmed by Western Blot analysis. 30 patients tested positive for ATLV by both immunoassay and Western blot analysis. ATLV rates among hemodialysis patients were significantly higher than rates among local blood donor populations. HIV infections are currently not as serious in Japan among hemodialysis patients as ATLV infections. The prevalence of ATLV infections among these patients was related 1st to blood transfusions 2nd to prevalence in the local population and 3rd to migration from endemic areas. If blood bank screening begun in 1986 is successful the probability of these infections being transmitted by blood transfusions will be greatly reduced.

Prevalence of HTLV-1 Antibodies in Hemodialysis Patients in Japan

The southwestern region of Japan is known as a very high endemic area of human T-cell lymphotropic virus type 1 (HTLV-1), the etiologic agent for adult T-cell leukemia (ATL) and probable causative agent for tropical spastic paraparesis and its Japanese version, HTLV-1-associated myelopathy (HAM). Hemodialysis (HD) patients seem to be at high risk for HTLV-1 infection even in other regions of Japan because they sometimes receive multiple blood transfusions. We examined antibody against ATL-associated antigen (ATLA-Ab) in 1,132 HD patients, including 1,066 patients in nonendemic areas (Chubu and Tokyo) and 66 in a highly endemic area (Okinawa). The HD patients in Okinawa showed the highest prevalence, 21.2% (14/66), while those in the Chubu area showed the lowest, 1.1% (10/846), and those in the Tokyo area an intermediate value, 2.7% (6/220). The prevalence of HD patients in each area was significantly higher than that of local blood donors, reflecting an increased prevalence roughly corresponding to the respective endemic rate. The average prevalence of ATLA-Ab among the HD patients was 2.7% (30/1,132), which was similar to that of HBs antigen (3.2%). In the nonendemic areas, 15 of 16 patients with ATLA-Ab had a history of blood transfusions, showing a significant correlation to the presence of ATLA-Ab (P less than 0.01), although four had family histories related to the endemic area. The relative risk of the presence of ATLA-Ab for HD patients with a history of blood transfusions was calculated as 10.3. In the endemic area of Okinawa, the relationship to blood transfusion was not so close, probably masked by the high background prevalence.

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.