Predictors of Survival in Chronic Hemodialysis Patients: A 10-Year Longitudinal Follow-Up Analysis.

BACKGROUND: Risk factors of mortality in chronic hemodialysis patients have not yet been sufficiently evaluated. In particular, chronological transits and interactions of the impact of risk factors have rarely been described. METHODS: This study is a post hoc analysis of the participants in the Olme-sartan Clinical Trial in Okinawan Patients under OKIDS (OCTOPUS) study conducted between June 2006 and June 2011. We additionally followed up on the prognosis of the participants until July 31, 2018. Standardized univariable and multivariable Cox regression analyses were used to evaluate the influences of the participants' baseline characteristics on all-cause mortality. We also evaluated chronological changes in the impacts of risk factors, interactions among predictors, and the influence of missing values using sensitivity analyses. RESULTS: Of the 469 original trial participants, 461 participants were evaluated. The median time of follow-up was 10.2 years. A total of 211 (45.8%) participants were deceased. The leading causes of death were infection (n = 72, 34.1%) and cardiovascular disease (n = 66, 31.3%). Univariate and multivariate Cox regression analyses revealed that the impact of diabetes mellitus, history of coronary intervention, and hypoalbuminemia were significant risk factors for mortality during the whole follow-up period. During the early follow-up period (≤3 years), standardized univariate Cox regression analyses revealed that history of amputation (hazard ratio [HR] = 4.61, p < 0.001), lower dry weight, higher cardiothoracic ratio, and lower potassium levels were statistically significant risks. In those who survived for longer than 3 years, a history of stroke (HR = 1.73, p = 0.006), higher systolic blood pressure, lower serum sodium levels, and higher levels of hemoglobin, and serum phosphate were significant risks. We also observed a stable interaction between the impacts of serum phosphate and albumin on all-cause mortality. CONCLUSION: In chronic hemodialysis patients, targets to improve the short-term prognosis and long-term prognosis are not equivalent. Hyperphosphatemia was a significant risk factor for the all-cause mortality among patients with normal serum albumin levels but not among patients with compromised albumin levels.

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).

Elevated resting heart rate is an independent predictor of all-cause death and cardiovascular events in Japanese ambulatory hemodialysis patients.

BACKGROUND: Elevated heart rate (HR) is an independent risk factor for all-cause death or cardiovascular events in non-hemodialysis subjects; however, the clinical significance of elevated HR in hemodialysis patients is not well studied. METHODS: We prospectively evaluated the relationship between HR and adverse outcome in a total of 229 ambulatory hemodialysis patients (57 % men; mean age 62.2 years) recruited from two dialysis clinics in 2009. Mean (SD) HR of this cohort was 74.1 (11.0) beats per minute (bpm). RESULTS: Receiver operating characteristic curves identified an HR cut-off level of ≥80 bpm for increased adverse outcome. After a mean follow-up of 525 days (range 7-760 days) a total of 30 primary endpoints (21 all-cause deaths, 4 acute coronary syndromes and 8 strokes) and 38 secondary endpoints (30 primary endpoints, 8 congestive heart failures, and 5 other cardiovascular events) were detected. Cox regression analysis revealed that HR >80 bpm was not an independent predictor of primary endpoints [hazard ratio 1.81, 95 % confidence interval (CI) 0.79-4.11, p = NS], but of secondary endpoints (hazard ratio 2.01, 95 % CI 1.01-4.22, p < 0.05) after adjusting for age, sex, hemodialysis duration, and cardiovascular risks. CONCLUSIONS: Elevated HR is an independent predictor of all-cause death and cardiovascular events in Japanese ambulatory hemodialysis patients.

Olmesartan clinical trial in Okinawan patients under OKIDS (OCTOPUS) study: design and methods.

BACKGROUND: Guidelines for treatment of hypertension are not available for chronic hemodialysis (HD) population, despite the high mortality rate due to cardiovascular disease (CVD). Survival is much better among hypertensive patients than normal to hypotensive patients. Target levels of blood pressure and the class of antihypertensive drugs have not been examined in prospective studies. METHODS: We designed a prospective randomized controlled study among hypertensive HD patients in Okinawa (Okinawa Dialysis Study, OKIDS). The outcomes will be compared between two treatment regimens, such as (1) renin-angiotensin system (RAS) inhibitor Olmesartan and others, and (2) antihypertensive drugs without RAS inhibitors, in a parallel fashion. The title of the study is Olmesartan Clinical Trial in Okinawan Patients under OKIDS (OCTOPUS). Outcomes are any cause of death and CVD in 3 years in a total of 462 patients. Subjects are age 20-79 years and ambulatory on thrice weekly HD treatment. Eligible patients have resistant hypertension: pre-HD session blood pressure 140/90 mmHg and over for more than 1 month regardless with the use of antihypertensive drugs. Patients treated with RAS drugs are eligible if they continue to be hypertensive for more than 1 month after switching to non-RAS antihypertensive drugs. CONCLUSION: This study provides evidence for the target levels of blood pressure at a pre-HD session and the impact of RAS inhibitors. We also evaluate the usefulness of home blood pressure monitoring in HD patients.

Significance of coronary artery calcification score (CACS) for the detection of coronary artery disease (CAD) in chronic dialysis patients.

BACKGROUND: Coronary artery disease (CAD) is a principal cause of death in patients with end-stage renal disease (ESRD). The coronary artery calcification score (CACS), determined by electron-beam computed tomography (EBCT), is useful for the detection of CAD in non-ESRD patients. There are few reports on the usefulness of EBCT for the detection of CAD, however, in ESRD patients. We examined the relation between CACS and CAD in ESRD patients. METHODS: Coronary angiography (CAG) was used to diagnose CAD in patients with significant coronary artery stenosis (>or=50%). We examined 76 ESRD patients on chronic dialysis therapy from 1997 to 2005, of which 51 are men, 25 are women, mean (S.D.) age of 57.9 (12.1) years and mean (S.D.) HD duration of 7.7 (6.6) years. There were 50 (35 men, 15 women) patients with CAD and 26 (16 men, 10 women) without CAD. RESULTS: The median CACS was 1290 in all patients, 1689 in the CAD group and 527 in the non-CAD group; the mean (S.D.) CACS was 1833 (2003) in all patients, 2338 (2209) in the CAD group and 861 (991) in the non-CAD group. CACS was significantly higher in the CAD group than in the non-CAD group. The CACS cutoff values for predicting CAD were calculated at intervals of 100. At the cutoff values of >or=100, >or=500, >or=1000, >or=2000, and >or=3000, the sensitivity was 98%, 90%, 68%, 42%, and 32% and the specificity was 35%, 50%, 69%, 85%, and 96%, respectively. CONCLUSIONS: EBCT is not adequate for screening asymptomatic ESRD patients. Because EBCT is less invasive than CAG, further study is necessary to determine whether CAG should be performed in all high-risk ESRD patients on chronic dialysis.

Outcome study of renal biopsy patients in Okinawa, Japan.

Here we report a community-based epidemiologic study of patients who received renal biopsy in Okinawa, Japan between 1967 and 1994. The total number of cases was 2832 (1395 men and 1437 women), and the mean (SD) age at biopsy was 30.0 (10.0) years (range 1.0 to 88.0 years). The most common clinical indications for renal biopsy were proteinuria/hematuria (46.7%), nephrotic syndrome (21.2%), acute glomerulonephritis (10.1%), and systemic lupus erythematosus (7.5%). Patients who received renal biopsy between 1985 and 1994 (N= 1480) were much less likely to have acute glomerulonephritis than patients treated between 1967 and 1984 (N= 1352); the rates of proteinuria/hematuria, renal failure, and diabetes mellitus were slightly higher in the later period. Okinawa patients who began dialysis between 1971 and 2000 (N= 5246) were also studied. Among them, a total of 468 patients (260 men and 208 women) began dialysis after renal biopsy. The cumulative incidence of end-stage renal disease (ESRD) among these patients was 17% in 17 years. Half of these patients developed ESRD in the 5.8 years after renal biopsy. Among the dialysis patients, the biopsy rate was 12.6% in chronic glomerulonephritis, 1.7% in diabetes mellitus, 2.6% in nephrosclerosis, and 52.1% in systemic lupus erythematosus. The diagnoses of primary renal diseases were primarily made clinically. The survival rate after starting dialysis therapy was slightly better in those with than in those without renal biopsy but this finding was not statistically significant (adjusted hazards ratio 0.855, 95% CI 0.711-1.028, P= 0.095). The clinical significance of renal biopsy, other than its provision of histologic evidence, remains to be shown.