A new peritoneal dialysis fluid for Japanese patients: a randomized non-inferiority clinical trial of safety and efficacy.

BACKGROUND: We report here two new peritoneal dialysis fluids (PDFs) for Japan [BLR 250, BLR 350 (Baxter Limited, Japan)]. The PDFs use two-chamber systems, and have bicarbonate and lactate buffer to a total of 35 mmol/L. In separate trials, the new PDFs were compared to two "standard" systems [PD-4, PD-2 (Baxter Limited, Japan)]. The trials aimed to demonstrate non-inferiority of peritoneal creatinine clearance (pCcr), peritoneal urea clearance (pCurea) and ultrafiltration volume (UF), and compare acid-base and electrolyte balance. METHODS: We performed randomized, multicenter, parallel group, controlled, open-label clinical trials in stable continuous ambulatory peritoneal dialysis (CAPD) patients. The primary endpoints were pCcr and UF. The secondary endpoints were serum bicarbonate and peritoneal urea clearance. The active phase was 8 weeks. These trials were performed as non-inferiority studies, with the lower limit of non-inferiority for pCcr and UF set at 3.2 L/week/1.73 m2 and 0.12 L/day, respectively. RESULTS: 108 patients (28 centers) and 103 patients (29 centers) took part in the two trials. Groups were well balanced at baseline. The investigative PDFs were non-inferior to the "standard" ones in terms of primary endpoints, comparable in terms of pCurea, and superior in terms acid-base balance, especially correcting those with over-alkalinization at baseline. CONCLUSIONS: We demonstrated fundamental functionality of two new PDFs and showed superior acid-base balance. Given the propensity of Japanese CAPD patients for alkalosis, it is important to avoid metabolic alkalosis which is associated with increased cardiovascular mortality risk and accelerated vascular calcification. The new PDFs are important progress of CAPD treatment for Japanese patients.

Markers in peritoneal effluent for withdrawal from peritoneal dialysis: multicenter prospective study in Japan.

The most serious problem in peritoneal dialysis (PD) is the risk of final complication by encapsulating peritoneal sclerosis (EPS) because of peritoneal deterioration. Markers useful for the noninvasive evaluation ofperitoneal deterioration are therefore required. In this multicenter prospective study of stable PD patients, we compared the dialysate-to-plasma (D/P) concentration ratios of albumin, immunoglobulin G, and c2-macroglobulin, and effluent levels of interleukin 6 (IL-6) and fibrinogen/fibrin degradation products (FDPs) to clarify the relationship between inflammation, fibrinolysis markers, and permeability to large molecules. At the beginning of the present study, significantly positive correlations were noted between the IL-6 and FDP concentrations and the D/P ratios of albumin and a2-macroglobulin. In addition, a significantly positive correlation was noted between the FDP and IL-6 concentrations. However, the D/P ratio of creatinine obtained by peritoneal equilibration test did not positively correlate with those markers. Moreover, a significantly positive correlation was noted between changes in the effluent concentrations of FDPs and IL-6 and in permeability markers for large molecules. The effluent IL-6 and FDP concentrations reflect a chronic inflammatory state in the peritoneum, which is associated with increased permeability to large molecules. In individual PD patients, careful observation of the clinical course and evaluation of changes in such markers are expected to predict peritoneal deterioration and the development of EPS.

Intima-media thickness of carotid artery predicts cardiovascular mortality in hemodialysis patients.

BACKGROUND: Cardiovascular disease is the leading cause of death in patients with end-stage renal disease (ESRD). Previous studies showed that patients with ESRD had increased intima-media thickness of the carotid artery (CA-IMT). In the present study, we examined whether CA-IMT would predict cardiovascular mortality in patients with ESRD. METHODS: The cohort consisted of 438 patients with ESRD treated with hemodialysis. CA-IMT was measured by high-resolution B-mode ultrasonography. RESULTS: During the follow-up period of 30 months, 82 deaths, including 44 cardiovascular fatal events, occurred. Compared with those with CA-IMT less than 1.0 mm, those with moderately increased CA-IMT (1.0 to 2.0 mm) and those with severely increased CA-IMT (>or=2.0 mm) showed a significantly greater risk for death from cardiovascular causes; odds ratios were 3.17 (95% confidence interval [CI], 1.41 to 7.17; P = 0.005) and 10.20 (95% CI, 3.67 to 28.3; P < 0.0001), respectively, in a multivariate Cox analysis including age, sex, duration of hemodialysis therapy, presence of diabetes mellitus, blood pressure, body mass index, and high-density lipoprotein and non-high-density lipoprotein cholesterol levels as covariates. Conversely, CA-IMT was not significantly associated with noncardiovascular mortality. CONCLUSION: These results indicate that increased CA-IMT is an independent predictor of cardiovascular mortality in the hemodialysis population.

Body fat mass in hemodialysis patients.

BACKGROUND: Changes in body fat mass in a large number of hemodialysis patients is unknown. METHODS: Body fat mass and lean body mass were measured by dual x-ray absorptiometry (DXA) in 561 patients with hemodialysis duration less than 180 months (62.3 +/- 11.5 years old; mean +/- SD). RESULTS: Fat mass tended to increase during the first 3 years of hemodialysis, and it tended to decrease thereafter. Between hemodialysis duration and the fat mass index, there was a significant positive correlation within the first 36-month period of hemodialysis (r = 0.124; P < 0.05; n = 245), and a significant negative correlation during the period of 36 to 180 months. (r = -0.192; P < 0.001; n = 316). There was no tendency of change in the lean body mass index. CONCLUSION: Considering the results together with the authors previous prospective study results, which show significant fat mass increase in the first year of hemodialysis, the present cross-sectional study may suggest that fat mass gradually increases in the first 3 years and decreases thereafter. Fat mass is suggested to be a nutritional parameter in hemodialysis patients.

Clinical usefulness of the serum N-terminal propeptide of type I collagen as a marker of bone formation in hemodialysis patients.

BACKGROUND: An intact collagen I amino-terminal propeptide (PINP) assay has been developed as a useful assay for bone formation. The present study was performed to investigate the clinical usefulness of serum PINP as a bone-formation marker in hemodialysis (HD) patients. METHODS: PINP and other bone-formation markers, ie, bone alkaline phosphatase (BAP) and intact osteocalcin (OC), were determined in serum samples collected from 209 HD patients. RESULTS: Serum PINP levels, in contrast to serum BAP and OC levels, did not change significantly during a single HD session (P = 0.069; n = 14). There were significant positive correlations between serum PINP and BAP (r = 0.723; P < 0.001) and OC values (r = 0.739; P < 0.001), as well as intact parathyroid hormone (r = 0.652; P < 0.001) and bone-resorption marker values: deoxypyridinoline (DPD; r = 0.823; P < 0.001), pyridinoline (PYD; r = 0.735; P < 0.001), and beta-crosslaps (r = 0.705; P < 0.001). Serum PINP values correlated significantly more strongly than serum BAP values with all bone-resorption markers. Serum PINP values significantly correlated negatively with annual changes in bone mineral density (BMD) in the distal third of the radius (r = -0.286; P < 0.001). When subjects were divided into tertiles according to degree of bone loss, subjects with greater bone loss had significantly greater serum PINP, BAP, and OC levels, although PINP and OC provided greater discrimination than BAP. PINP-PYD and PINP-DPD ratios, indices of osteoblast function not confounded by enhanced bone resorption, significantly positively correlated with annual BMD changes in the distal third of the radius (PINP-PYD ratio, P = 0.008; PINP-DPD, P = 0.015). CONCLUSION: Serum PINP may provide a better marker of osteoblast function in HD patients and thus be clinically useful for predicting radius bone loss.

[Sibling cases of nephritis resembling membranoproliferative glomerulonephritis].

We have experienced rare cases of membranoproliferative glomerulonephritis (MPGN)-like nephritis, which was seen in siblings. Both the brothers had asymptomatic hematuria and proteinuria at an age before 10, 7 and 4 years old, respectively. Renal biopsy revealed proliferative glomerulonephritis, resembling MPGN type III. The family history showed that their father and grandfather suffered from end-stage renal disease, suggesting that MPGN seen in the present sibling cases is hereditary. A review of the literature revealed that familial MPGN is rare, that most of the cases have urinary abnormalities at an age of less than 10 years, and that male preponderance is seen in familial MPGN.

Impaired secretion of parathyroid hormone, but not refractoriness of osteoblast, is a major mechanism of low bone turnover in hemodialyzed patients with diabetes mellitus.

Diabetic bone disease is characterized by low bone turnover resulting from either impaired secretion of parathyroid hormone (PTH) or refractoriness of osteoblasts to PTH. The present study was performed to elucidate which factor contributes more to the reduction in bone turnover by comparison between 64 hemodialyzed patients with diabetes mellitus and 106 hemodialyzed patients without diabetes mellitus. Only men were enrolled to avoid the influence of the menstrual cycle on bone metabolism. Serum intact PTH (iPTH) levels were significantly lower in hemodialyzed patients with diabetes than those without diabetes, although no significant difference existed in age, duration of hemodialysis therapy, or serum calcium or phosphate levels. Of the biochemical markers measured, serum intact osteocalcin (iOC) and deoxypyridinoline levels were significantly lower in patients with diabetes, although serum bone-specific alkaline phosphatase (BAP) and pyridinoline levels did not differ significantly between the two groups of patients. When patients were restricted to those with serum iPTH levels greater than 180 pg/mL, this parameter correlated significantly in a positive manner with both serum iOC and BAP levels and negatively with bone mineral density at distal radius 1/3. Regression slopes between iPTH levels and these parameters were not significantly different between the two groups of patients, indicating the absence of refractoriness of bone to PTH in patients with diabetes. In conclusion, our findings suggest that impaired PTH secretion, but not refractoriness of osteoblasts to PTH, may be responsible for the low bone turnover in hemodialyzed patients with diabetes.

Increasing body fat mass in the first year of hemodialysis.

Nutritional status affects well-being and survival in patients who are undergoing hemodialysis. It was examined how maintenance hemodialysis altered body fat mass. In 72 patients with chronic renal failure (age, 62 +/- 12 yr; 42 men, 30 women), body fat was measured by dual x-ray absorptiometry 1 mo after initiation of maintenance hemodialysis and approximately 1 yr later (mean +/- SD, 11 +/- 2 mo). The second measurement showed significantly greater body fat mass than the first (11.38 +/- 3.84 versus 10.09 +/- 4.12 kg; P < 0.0001). After calculation of the change in body fat mass per month, no significant differences were evident in relation to gender or to presence of diabetes. Changes in body fat mass per month correlated negatively with baseline serum albumin concentration (r = -0.449, P < 0.0001) and baseline body fat mass (r = -0.423, P < 0.001). These factors independently influenced the change according to multiple regression analysis (R(2) = 0.323, P < 0.0001). In conclusion, body fat mass increases significantly in the first year of maintenance hemodialysis, especially in patients with poor nutritional status. More general, dual x-ray absorptiometry assessment of body fat mass was found to be useful for evaluating the nutritional status of hemodialysis patients.