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Background Cardiovascular disease is the leading cause of mortality in patients with kidney failure treated with hemodialysis (HD). Although angiotensin receptor blockers (ARBs) reduce cardiovascular disease (CVD) events in patients with diabetes and chronic kidney disease, their effect in patients with kidney failure on HD therapy is not known. Study Design Open-labeled randomized trial. Setting & Participants Patients aged 30 to 80 years receiving HD 2 to 3 times weekly for 1 to 5 years at 5 university-affiliated dialysis centers. Interventions Treatment with ARBs (valsartan, candesartan, and losartan) versus without ARBs after stratification by sex, age, systolic blood pressure, and diabetes. Outcomes The primary end point is the development of fatal and nonfatal CVD events, defined as the composite of CVD death, myocardial infarction, stroke, congestive heart failure, coronary artery bypass grafting, or percutaneous coronary intervention. The secondary end point is all-cause death. Results 366 subjects initially were randomly assigned to an ARB or no ARB (control), but after a run-in phase, 180 were retained in each group. Mean age was 60 years, 59% were men, 51% had diabetes, and mean predialysis systolic blood pressure was 154 mm Hg. There were 93 fatal or nonfatal CVD events (52%); 34 (19%) in the ARB group and 59 (33%) in the non-ARB group. After adjustment for age, sex, diabetes, systolic blood pressure, and center, treatment with an ARB was independently associated with reduced fatal and nonfatal CVD events (hazard ratio, 0.51; 95% confidence interval, 0.33 to 0.79; P = 0.002). There were 63 deaths (35%); 25 (14%) in the ARB group and 38 (21%) in the non-ARB group. After adjustment, all-cause mortality differed between the 2 groups (hazard ratio, 0.64; 95% confidence interval, 0.39 to 1.06; P = 0.1). Limitations Because of the small sample size of this trial, the large effect may be a spurious finding. Use of an open-label design and 3 different agents in the ARB group might have influenced results. Conclusion Use of an ARB may be effective in reducing nonfatal CVD events in patients undergoing long-term HD. A larger study is required to confirm these results.

Background: Cardiovascular diseases constitute major causes of death in patients with chronic kidney diseases. An increase in arterial stiffness predicts the presence of cardiovascular diseases; however, non-invasive arterial stiffness parameters such as pulse wave velocity are confounded by blood pressure.Methods: A new arterial stiffness parameter β for the arterial tree, cardio-ankle vascular index (CAVI), was measured. To examine the usefulness of CAVI to screen for the presence of cardiovascular diseases, cross-sectional studies were performed on 68 patients undergoing chronic hemodialysis.Results: Stepwise regression analysis indicated that CAVI significantly correlated to age (β=0.05, p

Evidence suggests that the effectiveness of angiotensin-converting enzyme (ACE) inhibition diminishes with time, resulting in increasing angiotensin II levels, the action of which can be inhibited by the addition of an angiotensin receptor blocker (ARB). In the present study, the renal protective effects of ACE inhibitors and ARBs were compared over a five-year period in a prospective, randomized, open-blind study in 68 nondiabetic Japanese patients with elevated serum creatinine levels.Japanese patients with renal insufficiency were randomly assigned to receive either an ACE inhibitor (benazepril 1.25 to 5 mg daily or trandolapril 0.5 to 4 mg daily) or ARB (candesartan 2 to 8 mg daily or losartan 25 to 100 mg daily) at the Kidney Disease Center at Saitama Medical School Hospital. The primary study endpoint was a change in glomerular filtration rate (GFR) between the baseline value and the last available value obtained during the five-year treatment period, as estimated by the Cockcraft-Gault equation. Secondary endpoints included the annual changes in GFR, serum creatinine level, urinary protein excretion, and blood pressure, as well as the rate of development of endstage renal disease.There were no significant differences in the primary endpoint between the two groups. However, after 4 years, the decline in GFR in patients treated with ARBs was significantly greater than that seen in patients treated with an ACE inhibitor (p0.05). Furthermore, the rate of introduction of dialysis therapy was also significantly greater in the ARB-treated patients (52.7% in ACE inhibitor and 81.2% in ARB group at year 5. p0.01).While our data suggested that ARB, like ACE, treatment might slow the progression of renal dysfunction, it also pointed to the necessity to be alerted to the progression to endstage renal disease with longterm medication.

In the past, hyperparathyroidism was not generally a major problem in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). However, in conjunction with disturbances in serum phosphate, Ca, and CaxP product, hyperparathyroidism has become a serious problem in the cardiovascular diseases of patients with end-stage renal disease-even patients undergoing CAPD. We retrospectively evaluated the first 5 years on CAPD for 17 patients who started and continued dialysis between April 1995 and September 2003. Of these 17 patients, 3 underwent parathyroidectomy. During their clinical course, all of the patients experienced a decline in residual renal function (RRF) that was significantly negatively correlated with their levels of serum Ca and intact parathyroid hormone. Based on these findings, we suggest that RRF is an important factor for the regulation of Ca-P metabolism in patients on CAPD.

Many patients undergoing continuous ambulatory peritoneal dialysis (CAPD) receive antihypertensive agents, including calcium antagonists, which produce reflex tachycardia through activation of the sympathetic nervous system. Azelnidipine, a newly developed calcium antagonist, has unique characteristics in that it causes less reflex stimulation of the sympathetic nervous system. In the present study, we used a crossover method to compare the effects of amlodipine (5-10 mg daily) and azelnidipine (8-16 mg daily) on drain volume and weekly creatinine clearance in 9 CAPD patients (3 women, 6 men; mean age: 64 +/- 5 years; mean duration of CAPD: 1.8 +/- 0.6 years). Each calcium antagonist was administered for 3 months and then switched for the other. As compared with amlodipine, azelnidipine increased drain volume by 13% +/- 2% (p0.05) and weekly creatinine clearance by 12% +/- 2% (p0.05). At the same time, we observed no significant differences in blood pressure and urine volume. The increases in drain volume produced by azelnidipine resulted from less activation of the sympathetic nervous system. We therefore suggest that activation of the sympathetic nervous system induced by calcium antagonists may be important in the regulation of drain volume in CAPD patients.

Although the use of continuous ambulatory peritoneal dialysis (CAPD) to treat refractory heart failure is not new, in combination with current medical treatment it improves patients'symptoms as well as their cardiac function. We started 16 patients (13 men with a mean age of 66.3 +/- 2.8 years, and 3 women with a mean age of 72 +/- 4.2 years) on CAPD. All patients were symptomatic with congestive heart failure. Mean left ventricular ejection fraction (LVEF) before the start of CAPD was 31% +/- 3%. Introduction to CAPD was associated with a significant improvement in LVEF (to 44% +/- 6%, p0.05) and in blood pressure control at 1 year. Also at 1 year, 87% of patients were classified as New York Heart Association grade I or II (maximum possible grade is grade III). These results suggest that CAPD is a treatment of choice for patients suffering from a combination of congestive heart failure and chronic renal insufficiency.

Peritonitis is a serious complication in patients on peritoneal dialysis. We examined the efficacy of MTV therapy [first 7 days: meropenem 0.5 g intravenously (IV) twice daily, plus tobramycin 15 mg intraperitoneally (IP) in every dialysis bag; next 7 days: meropenem 0.5 g IV twice daily, plus vancomycin 8 mg/kg IP in every bag after a 1-g loading dose] on peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), comparing it with the treatment previously recommended by the International Society for Peritoneal Dialysis (combination of first-generation cephalosporins and aminoglycosides). We treated 36 CAPD peritonitis episodes with MTV therapy. Outcome measures were primary response rate at day 14 and relapse rate within 28 days after the start of antibiotic therapy. The primary response rate was 34/36 (94.4%). No patients treated with MTV therapy required catheter removal. We observed no serious side effects in these patients. We conclude that MTV therapy may be an even better choice of treatment for peritonitis in patients on CAPD than was the previous empirical treatment (combination of first-generation cephalosporin and aminoglycosides).

The major cause of death in patients on peritoneal dialysis (PD) is vascular complications, including congestive heart failure, cerebrovascular disease, and myocardial infarction. To clarify the risk factors for vascular complications in patients on PD, we investigated the clinical course of PD in patients with and without cardiovascular and cerebrovascular complications. From among 327 end-stage renal disease (ESRD) patients initiated onto PD from April 1995 to March 2005 in the Kidney and Dialysis Center, Saitama Medical School, 8 developed de novo cardiovascular and cerebrovascular complications (CVD group--mean age: 58.3 +/- 4.9 years; 5 men, 3 women). We compared data pertaining to body weight, blood pressure, blood chemistry, and cardiothoracic ratio (CTR) between the CVD group and an age- and sex-matched control group (n = 8; mean age: 57.5 +/- 4.0 years). At baseline, we observed no significant differences of body weight, blood pressure, CTR, hemoglobin, total cholesterol, triglycerides, HbA1c, or serum albumin between the CVD group and the control group. In the CVD group, 1 month before the onset of CVD, serum albumin was significantly lower than in the control group (2.9 +/- 0.2 g/dL vs. 3.8 +/- 0.1 g/dL, p = 0.0029). Body weight in the CVD group was significantly lower than in the control group (56.8 +/- 2.8 kg vs. 63.0 +/- 2.9 kg, p = 0.0086). No significant differences were observed in blood pressure, CTR, hemoglobin, total cholesterol, triglycerides, or HbA1c between the groups. A decrease in serum albumin after commencement of dialysis is an important risk factor for, and a strong predictor of vascular complications in patients on PD. To help prevent vascular complications, it is important to monitor and manage serum albumin in patients on PD.