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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: Both residual renal function and blood pressure (BP) control contribute to patient survival in patients receiving continuous ambulatory peritoneal dialysis (CAPD). It is unknown whether antihypertensive drugs affect residual renal function in addition to BP reduction. Methods: We examined the effects of an angiotensin II receptor blocker, valsartan, on residual renal function and total clearance (renal and peritoneal) in 34 Japanese CAPD patients from 3 months to 2 years after the start of dialysis therapy. Patients were randomly assigned to valsartan (n = 18; age, 63.5 ± 3.7 years; 11 men, 7 women) or a control group (n = 16; age, 63.5 ± 3.3 years; 10 men, 6 women). Conventional antihypertensive treatment was continued in all patients to achieve the target BP in both groups of 130/80 mm Hg or less, measured at home. Results: BP reduction was similar in the valsartan and control groups. Valsartan significantly slowed the progressive decline in both residual renal function (3.2 ± 0.3 to 4.3 ± 0.7 mL/min/1.73 m 2 ) and total clearance (42.1 ± 3.2 to 48.3 ± 4.8 L/wk/1.73 m 2 ) by dialysis in CAPD patients compared with controls (5.9 ± 0.5 to 2.8 ± 0.4 mL/min/1.73 m 2 ; 47.1 ± 4.8 to 31.4 ± 5.2 L/wk/1.73 m 2 ). Conclusion: This study shows that in patients with hypertension starting CAPD therapy, valsartan slows the decline in residual renal function and contributes to maintenance of weekly creatinine clearance and Kt/V (fraction per dialysis), which are the major factors contributing to the mortality and morbidity of CAPD patients. This effect appears to be mostly a result of maintaining residual renal function.

A number of patients with multiple organ failure (MOF) regardless of accompanying acute renal failure have been treated with continuous hemodiafiltration (CHDF). However, despite its high cost, the costs/benefits of CHDF for MOF patients still need to be evaluated. Although many scoring systems were established to predict the outcome of MOF, their predictive powers were not estimated in MOF patients undergoing CHDF. Therefore, using 52 Japanese patients with MOF treated with CHDF for more than 1 week, we estimated the predictive powers of multiple organ dysfunction (MOD) scores and acute physiology and chronic health evaluation (APACHE) III scores, retrospectively. The patients were divided into 2 groups according to outcome at Day 28 after the initiation of CHDF. In both scoring systems, the median values at Day 0 were not significantly different between the survival (n = 19) and the nonsurvival (n = 33) groups. In contrast, at Day 3, the median values of MOD scores was 4 (0-14) in the survival group and 9 (1-12) in the nonsurvival group (p = 0.0035). The median value of APACHE III scores were 37 (19-97) and 87 (16-150) at Day 3, respectively (p < 0.0001). In the survival group, APACHE III scores significantly decreased from the median value of 64 (32-89) to 37 (p = 0.0269), and in the nonsurvival group, it increased significantly from the median value of 70 (29-103) to 87 (p = 0.0116). In contrast, no significant changes were observed in the MOD scores. In conclusion, the MOD score and the APACHE III score systems had less power to predict the outcome of MOF patients undergoing CHDF at Day 0. However, rescoring at Day 3 of each index was much more powerful to accurately predict the outcome of such patients.

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.

The purpose of this study is to retrospectively analyze the clinical characteristics of patients with diabetes mellitus who started dialysis therapy. First, we reviewed 120 cases of end-stage renal failure due to diabetic nephropathy who started dialysis therapy in 1996 and 1997. Presenting features were as follows: men, 62.5%; mean age at starting dialysis, 57 +/- 1 year; and mean serum creatinine level, 7.3 +/- 0.2 mg/dl. To find any clinical characteristics in the population, we divided patients into three groups according to age, as follows: Young age group (40 years old: 12 patients), Senior age group (65 years: 32 patients) and Middle age group: 76 patients (40 and65 years). The Young age group, (mean age: 36 +/- 1 years) had lower serum creatinine levels (6.1 +/- 0.4 mg/dl) (p0.05) and greater cardio-thoracic ratio (61.1 +/- 1.3%) (p0.05), obtained from the chest X-ray film, than the other two groups. There were no significant differences between the Middle age group (59 +/- 1 year) and the Senior age group (72 +/- 1 year) in the levels of serum creatinine and cardio-thoracic ratio. To further analyze the clinical characteristics, the other 113 patients in 1998 and 1999 who were matched with the Middle age group in the former study, were retrospectively analyzed. The mean age was 61 +/- 2 years, and the proportion of men was 54% (62/113). The percentage of changes in body weights were as follows: 9.5 +/- 2.8% (p0.05) from teens to 20s and 19.2 +/- 3.2% (p0.05) from teens to 30s in men. The percentage of changes in body weight in women were as follows: 9.6 +/- 2.1% (p0.05) from teens to 30s and 18.6 +/- 2.4% (p0.05) from teens to 40s. The age at the start of dialysis therapy was 54 +/- 2 years old in men and 59 +/- 3 years in women. There was a significant difference (p0.05) between men and women. In summary, the study suggests that young patients with diabetic nephropathy received dialysis therapy because of hypervolemic symptoms compared to older patients, and that renal deterioration progressed more rapidly in male subjects than in female subjects with diabetic nephropathy. These differences should be borne in mind in clinical practice.

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).

Continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) both have advantages in the treatment of patients with renal failure. In CAPD, solute removal is sometimes insufficient in patients who have a relatively large muscle mass that produces high levels of creatinine. To compensate for this deficiency, frequent exchanges and large dialysate volumes are required. We previously reported that once-weekly HD helps CAPD patients who experience insufficient solute removal. In the present study, we followed, for more than 3 years, 9 CAPD patients who underwent additional weekly HD. Add-on HD therapy significantly increased the subjects' weekly peritoneal creatinine clearance to 45 +/- 3 L (mean +/- standard deviation); these values rose to more than 60 L over the course of the study. Our findings suggest that the combined use of CAPD and HD improves solute clearance in CAPD patients who are insufficiently dialyzed.

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.

The influence that the mode of dialysis has on the prognosis of patients with renal disease is controversial. The controversy arises at least in part because of the heterogeneity of patient populations, who may be receiving either continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD). In the absence of randomized trials, epidemiologic investigations present the best method for studying the problem. To determine the influence of the mode of dialysis on prognosis and on the cardiovascular system, erythropoiesis, and calcium metabolism, we selected 36 patients undergoing CAPD and 36 patients undergoing HD for a 3-year follow-up study. Patients were matched for age, sex, and cause of renal disease. Among the HD patients, 8 deaths occurred from congestive heart failure, 1 death from cerebrovascular accident, and 2 deaths from severe infection. In the HD group, the average age was 63 +/- 3 years. Among the CAPD patients, 6 were transferred to HD because of recurrent peritonitis or elevation of serum creatinine. Patients on CAPD had lower blood pressures, and patients on HD had lower total cholesterol levels. Other parameters were not significantly different between the two groups, including dose of erythropoietin and calcium supplements administered. Our study provides evidence that clinical outcome in renal failure may depend to some extent on the mode of dialysis. Our results suggest that blood pressure level and serum cholesterol should be taken into account for patients treated with either CAPD or HD. Blood pressure and cholesterol level are both likely to be important contributors to mortality and morbidity in renal patients.

We successfully used argon plasma coagulation (APC) to treat two cases of dialysis patients with hemorrhagic gastric angiodysplasia. Gastric angiodysplasia is recognized as an important cause of gastrointestinal bleeding. Angiodysplastic lesion confined to the gastric antrum was first described in 1953 and named gastric antral vascular ectasia (GAVE). The condition is characterized as submucosal capillary dilatation and fibromuscular hyperplasia. The typical finding of GAVE is the so-called watermelon stomach, attributable to vasodilatation. In case 1, a 69-year-old man was introduced continuous ambulatory peritoneal dialysis (CAPD) in July 1997 because of chronic renal failure due to nephrosclerosis. He was hospitalized for severe anemia in December 1997. Gastrointestinal fiberscopy (GIF) showed oozing in the antrum, and gastritis and esophagitis with sliding hernia. Famotidine was started and recombinant human erythropoietin (rHuEPO) was used for anemia. However, the severe anemia did not improve. The patient was hospitalized again for severe anemia and hematemesis. Another GIF showed typical watermelon stomach, which corresponded with GAVE. An APC was performed without complications. Three months later, the anemia was improved, and the dose of rHuEPO was reduced. In case 2, a 57-year-old woman was introduced to hemodialysis in 1998 for uremia due to nephrosclerosis. In October 2000, she was hospitalized for rHuEPO-resistant anemia. A GIF showed oozing in the antrum with diffuse vasodilation in the antrum; GAVE was diagnosed. An APC was carried out without complications. Three months later, anemia was improved. Recently, gastric angiodysplasia was reported to be an important complication in dialysis patients and was recognized as an important cause of rHuEPO-resistant anemia. Argon plasma coagulation is an effective treatment for gastric angiodysplasia in patients on dialysis.

In the present study, we investigated longitudinal changes in peritoneal function, as calculated by the personal dialysis capacity (PDC) test, after patient withdrawal from 17 years of continuous ambulatory peritoneal dialysis (CAPD). In July 1982, a 42-year-old female was started on CAPD because of chronic renal failure. She performed CAPD without any trouble for 17 years. In July 1999, hemodialysis was introduced because of ultrafiltration failure. The CAPD catheter remained in place, and the patient subsequently performed intra-abdominal lavage, using a standard peritoneal dialysis (PD) solution, for 3 years. A PDC test was performed every 6 months before and after withdrawal from CAPD. In July 1999, the PDC test indicated a membrane area of 59,748 cm/1.73 m2, absorption of 2.72 mL/min/1.73 m2, plasma loss of 0.049 mL/min/1.73 m2, and ultrafiltration volume (UFV) of -666 mL/24 h. The dialysate-to-plasma ratio (D/P) of creatinine after 4 hours was 0.96. An abdominal computed tomography (CT) scan showed calcification of the peritoneum. In March 2000, the PDC showed an area of 44,929 cm/1.73 m2, absorption of 1.43 mL/min/1.73 m2, plasma loss of 0.092 mL/min/1.73 m2, and alpha UFV of 213 mL/24 h. In August 2000 (1 year after CAPD withdrawal), the area was 38,492 cm/1.73 m2; the absorption, 1.74 mL/min/1.73 m2; the plasma loss, 0.053 mL/min/1.73 m2; and the UFV, 348 mL/24 h. Long-term intra-abdominal lavage induced a gradual reduction in membrane area, which returned to the normal range (19,028 cm/1.73 m2) after 3 years. Ultrafiltration volume showed a gradual increase and reached its peak level (403 mL/24 h) in July 2002. After 3 years, the D/P creatinine was 0.82. However, an abdominal CT scan showed no change in the calcification of the peritoneum. From those data, we conclude that, in long-term CAPD patients, intra-abdominal lavage can induce improvement in peritoneal function, but not in calcification of the peritoneum.

We investigated whether a selective angiotensin II receptor blocker (ARB) would have a regressive effect on left ventricular hypertrophy (LVH) in patients on continuous ambulatory peritoneal dialysis (CAPD). In a double-blind study, 24 CAPD patients with LVH [left ventricular mass index (LVMi)110 g/m2 for women and LVMi137 g/m2 for men] were randomized to 12 months' administration of either the ARB valsartan (n = 14) or a placebo (n = 10). The target blood pressure (BP) was 140/90 mmHg or lower in both groups. The following parameters were measured before and at the end of the study: aortic and large-artery compliance and arterial wave reflections [pulse wave velocity (PWV) and augmentation index (AI) application tonometry] and cardiac echocardiography. Periodically recorded were body weight, BP (mercury sphygmomanometer), serum creatinine, electrolytes, complete blood cell counts, urine volume, drainage volume, and weekly creatinine clearance. Two-way analysis of variance for repeated measurements was used for statistical analysis. Systolic and diastolic BP were both reduced in patients treated with ARB. The LVMi was significantly reduced in patients treated with ARB (to 121 +/- 4 from 145 +/- 5) but not in those receiving placebo (to 137 +/- 3 from 152 +/- 3, p0.05). The decrease in LVMi was associated with a reduction in PWV and AI. In CAPD patients with LVH, ARB reduced LVMi in association with alterations in arterial hemodynamics.

Background. No satisfactory treatment exists for IgA nephropathy (IgAN), especially in patients with severe histologic damage. Several trials using steroids combined with other therapies such as warfarin have demonstrated unremarkable results. We investigated the renoprotective effects of warfarin and steroids in IgAN patients with crescent formation. Methods. Fifteen Japanese patients with IgAN were followed for up to 3 years. Crescent formation was recognized in over half of their glomeruli from renal biopsy specimens. Treatments consisted of either 0.5 mg/kg per day of prednisolone, or warfarin monotherapy. Blood pressure was controlled with long-acting calcium channel blockers and alpha-beta blockers. Serum creatinine and urinary protein excretion were evaluated at least every 2 months for 36 months. Results. Ten of the 15 patients completed the study. The serum creatinine levels had increased in both groups by 3 years, but significantly more so in the group treated with warfarin. However, they were not significantly different between the two groups as measured at the beginning and end of the study. Blood pressure for all patients in the study was maintained below 130/85 mmHg. Excluded from the study were 5 patients who experienced either peptic ulcers (n = 2, steroid group) or bleeding problems (n = 3, warfarin group). Conclusions. These results suggest that corticosteroid therapy may assist in preventing deterioration of renal function in patients with IgAN accompanied by crescent formation. However, further study would be required to decide its usefulness.

Systemic capillary leak syndrome (SCLS) is characterized by recurrent hypovolemic shock attributable to increased systemic capillary leakage. A 46-year-old man was admitted to our hospital because of recurrent episodes of generalized edema with hypovolemic shock. Blood laboratory data revealed severe hypoproteinemia with a small monoclonal IgG-kappa protein. These findings suggested strongly the diagnosis of SCLS. A regimen with steroid pulse therapy was tried; however, intravascular overloading accompanied by the recruitment of the initially extravasated fluids resulted in acute pulmonary edema. Intensive care and careful monitoring of fluid volume are required in SCLS.

The objective of this study was to analyze retrospectively the efficacy of polymyxin-B immobilized fiber (PMX-F) alone and in combination with continuous venovenous hemofiltration (CHF) on the prognosis of critically ill patients with sepsis using a retrospective chart review in a university hospital in Japan. A cohort of 246 patients meeting the criteria of sepsis, septic shock, or both, according to the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/ACCM) Consensus Conference, were examined in this study. From these patients, 48 were selected who were found to have definitive causative bacteria and whose primary diseases were clearly identified. According to the charts, two major primary diseases were identified: one related to cardiovascular disease and the other to gastrointestinal disease. Other diseases were excluded from this study because of the small numbers of patients in categories such as malignant, hematological, genitourinary, and other diseases. Furthermore, patients who had levels of serum creatinine above 2.0 mg/dl were excluded. The prevalence of diabetes mellitus (up to 63%) was very high in both groups. There were no significant differences between the two groups in age or the Apache II scores at the start of hemoperfusion treatment; however, the gender ratio varied: 72% of the cardiovascular group were male, compared to 46% of the gastrointestinal group. The causative bacteria were markedly different between the two groups. For half of the gastrointestinal group the causative bacterium was Escherichia coli, while for half of the cardiovascular group the causative bacterium was Pseudomonas aeruginosa. The survival rate differed significantly between the two groups. The patients in the cardiovascular group survived longer than those in the gastrointestinal group. Moreover, for the patients with cardiovascular disease, there was no significant difference in the survival rate between treatment with PMX-F alone and with PMX-F and CHF in combination. In contrast, for the patients with gastrointestinal disease, there was a significant difference between treatment with PMX-F alone and with PMX-F and CHF in combination. When a patient with sepsis or septic shock is treated with hemoperfusion, the decision as to whether PMX-F should be given alone or in combination with CHF might be determined on the basis of the primary disease of the patient.

The aim of this study was first, to evaluate the effects of continuous hemodiafiltration (CHDF) alone or combined with CHDF and polymyxin-B immobilized fiber (PMX) on survival rates of patients with sepsis and acute renal failure, and second, to evaluate the changes in plasma levels of inflammatory cytokines before and after treatment with CHDF and PMX and CHDF alone in these patients. Forty-eight patients with septic shock and acute renal failure were enrolled in this study. The survival rate of all patients at 28 days was 25% for those with CHDF and 75% for those with PMX and CHDF treatment. Combination treatment produced a significant reduction of plasma levels of endotoxin and interleukin-6 compared to the basal values and to the treatment with CHDF alone. From these data, it is suggested that the combined therapy with PMX and CHDF is effective in improvement of survival rate of patients with septic shock and acute renal failure.