The serum vaspin levels are reduced in Japanese chronic hemodialysis patients.

BACKGROUND: Visceral adipose tissue-derived serine proteinase inhibitor (vaspin) is an adipokine identified in genetically obese rats that correlates with insulin resistance and obesity in humans. Recently, we found that 7% of the Japanese population with the minor allele sequence (A) of rs77060950 exhibit higher levels of serum vaspin. We therefore evaluated the serum vaspin levels in Japanese chronic hemodialysis patients. METHODS: Healthy Japanese control volunteers (control; n = 95, 49.9 ± 6.91 years) and Japanese patients undergoing hemodialysis therapy (HD; n = 138, 51.4 ± 10.5 years) were enrolled in this study, and serum samples were subjected to the human vaspin RIA system. RESULTS: The measurement of the serum vaspin levels demonstrated that a fraction of control subjects (n = 5) and HD patients (n = 11) exhibited much higher levels (> 10 ng/ml; Vaspin High group), while the rest of the population exhibited lower levels (< 3 ng/ml; Vaspin Low group). By comparing the patients in the Vaspin Low group, the serum vaspin levels were found to be significantly higher in the control subjects (0.87 ± 0.24 ng/ml) than in the HD patients (0.32 ± 0.15 ng/ml) (p < 0.0001). In the stepwise regression analyses, the serum creatinine and triglyceride levels were found to be independently and significantly associated with the vaspin concentrations in all subjects. CONCLUSIONS: The creatinine levels are negatively correlated with the serum vaspin levels and were significantly reduced in the Japanese HD patients in the Vaspin Low group.

Effects of icodextrin peritoneal dialysis solution on the peritoneal membrane in the STZ-induced diabetic rat model with partial nephrectomy.

BACKGROUND: Application of icodextrin-based peritoneal dialysis fluid (PDF) provides a potential benefit in patients with diabetes and end-stage renal failure treated with continuous ambulatory peritoneal dialysis (CAPD) because of better ultrafiltration capacity and avoidance of direct glucose exposure. We examined the effect of glucose and icodextrin-based PDF on histological alterations of peritoneal membranes. METHODS: Thirty-two male Wistar rats were divided into four groups: control Wistar rats with non-treated (n = 8), streptozotocin (STZ)-induced diabetic rats with 5/6 kidney ablation (n = 8), STZ-induced diabetic rats with 5/6 kidney ablation injected with a standard lactate-buffered 4.25% glucose-based PDF (Dianeal; n = 8) and STZ-induced diabetic rats with 5/6 kidney ablation injected with 7.5% icodextrin-based PDF (Extraneal; n = 8). Intraperitoneal injection was performed once daily with an instillation volume of 20 ml per injection during 8 weeks. RESULTS: Chronic high-glucose-based PDF exposure resulted in increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression, accumulation of advanced glycation end-products (AGEs), and up-regulation of the receptor for AGE (RAGE), which were ameliorated in the icodextrin-based PDF group. The peritoneal damages, such as neoangiogenesis and submesothelial fibrosis, were significantly reduced in icodextrin-based PDF compared to high-glucose-based PDF. CONCLUSIONS: Long-term in vivo exposure to high glucose-based PDF promotes the fibrosing process of peritoneal membranes. Icodextrin-based PDF may be helpful in slowing the PDF-induced deterioration of peritoneal function and prolonging the use of peritoneal dialysis in patients with diabetes.

Beta-blocker prescription and outcomes in hemodialysis patients from the Japan Dialysis Outcomes and Practice Patterns Study.

BACKGROUND/AIMS: Given the clear benefits of mortality reduction observed for most beta-blockers in clinical trials, they are relatively underused in hemodialysis patients. Since the outcomes associated with the use of beta-blockers are not fully known, we investigated their effect on mortality among a cohort of hemodialysis patients. METHODS: Data were analyzed from the Dialysis Outcomes and Practice Patterns Study phase II for 2,286 randomly selected patients on hemodialysis in Japan. Treatment with beta-blockers was the major predictor variable. The main outcome measure was all-cause mortality. Cox regression analysis was used to assess an association between treatment with beta-blockers and the risk of death. RESULTS: 247 patients (11.9%) were administered beta-blockers and 1,828 patients (88.1%) were not. Whereas patients treated with beta-blockers had a higher prevalence of hypertension and coronary heart disease, Kaplan-Meier analysis revealed that all-cause mortality rates were significantly (p < 0.007) decreased in patients treated with beta-blockers compared to those without. In multivariable, fully adjusted models, treatment with beta-blockers was also independently associated with reduced all-cause mortality (hazard ratio = 0.48; p = 0.02). CONCLUSION: This study indicated a possible association between the use of beta-blockers and reduced risk of mortality in hemodialysis patients. These results should be confirmed in further randomized controlled trials.

A case of immunotactoid glomerulopathy exhibiting nephrotic syndrome successfully treated with corticosteroids and antihypertensive therapy.

We report a case of immunotactoid glomerulopathy (ITG) with cerebral hemorrhage and hypocomplementemia, with successful therapeutic outcome following the corticosteroids and antihypertensive treatment. A 70-year-old man presented with facial edema in October 2006. One day prior to his referral, he experienced speech disturbance, headache, and vomiting, and on the next day he was referred to our hospital. The laboratory examination revealed massive proteinuria (11.3 g/day) and hematuria. The total serum hemolytic complement (CH50) was decreased to 23 U/ml and C4 component was decreased to 7.5 mg/dl, whereas C3 component remained within normal limits (82 mg/dl). Brain computed tomography scan showed high-density lesions in the left parieto-occipital area suggesting subcortical cerebral hemorrhage. Renal biopsy revealed diffuse subendothelial PAS-positive depositions. Immunofluorescence studies revealed intensive deposition of IgG, IgA, C3, C1q, Fibrinogen, and kappa light chain with granular pattern in the capillary and mesangial area. Electron microscopic examination revealed regularly arranged microtubular deposits, appearing as 21-33 nm in diameter. Based on these findings, this patient was diagnosed as ITG complicated with cerebral hemorrhage and hypocomplementemia. He received oral prednisolone (30 mg/day), resulting in reduction of proteinuria, improvement of hypocomplementemia, and prevention of renal functional deterioration. This case demonstrates that accurate diagnosis of ITG may result in successful therapeutic outcome.

Procollagen C-proteinase enhancer-1 (PCPE-1) interacts with beta2-microglobulin (beta2-m) and may help initiate beta2-m amyloid fibril formation in connective tissues.

Dialysis related amyloidosis (DRA) is a progressive and serious complication in patients under long-term hemodialysis and mainly leads to osteo-articular diseases. Although beta(2)-microglobulin (beta2-m) is the major structural component of beta2-m amyloid fibrils, the initiation of amyloid formation is not clearly understood. Here, we have identified procollagen C-proteinase enhancer-1 (PCPE-1) as a new interacting protein with beta2-m by screening a human synovium cDNA library. The interaction of beta2-m with full-length PCPE-1 was confirmed by immunoprecipitation, solid-phase binding and pull-down assays. By yeast two-hybrid analysis and pull-down assay, beta2-m appeared to interact with PCPE-1 via the NTR (netrin-like) domain and not via the CUB (C1r/C1s, Uegf and BMP-1) domain region. In synovial tissues derived from hemodialysis patients with DRA, beta2-m co-localized and formed a complex with PCPE-1. beta2-m did not alter the basal activity of bone morphogenetic protein-1/procollagen C-proteinase (BMP-1/PCP) nor BMP-1/PCP activity enhanced by PCPE-1. PCPE-1 did not stimulate beta2-m amyloid fibril formation from monomeric beta2-m in vitro under acidic and neutral conditions as revealed by thioflavin T fluorescence spectroscopy and electron microscopy. Since PCPE-1 is abundantly expressed in connective tissues rich in type I collagen, it may be involved in the initial accumulation of beta2-m in selected tissues such as tendon, synovium and bone. Furthermore, since such preferential deposition of beta2-m may be linked to subsequent beta2-m amyloid fibril formation, the disruption of the interaction between beta2-m and PCPE-1 may prevent beta2-m amyloid fibril formation and therefore PCPE-1 could be a new target for the treatment of DRA.

Increased susceptibility to oxidant-mediated tissue injury and peritoneal fibrosis in acatalasemic mice.

BACKGROUND: Peritoneal fibrosis is a major complication leading to the loss of peritoneal function in patients undergoing peritoneal dialysis. However, the effect of catalase depletion on peritoneal fibrosis has not yet been investigated. METHODS: The impact of catalase deficiency on progressive peritoneal fibrosis has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 14 days. RESULTS: The CG injections resulted in a thicker peritoneal membrane, reflecting peritoneal fibrosis with accumulation of interstitial type I collagen, peritoneal deposition of lipid peroxidation products (4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal), and an elevated level of 8-hydroxy-2'-deoxyguanosine in peritoneal fluid in both mouse groups on day 14. The extent of these changes, however, was significantly higher in acatalasemic mice than in wild-type mice. The level of catalase activity remained low in the acatalasemic peritoneum without the compensatory upregulation of glutathione peroxidase, but with an insufficient upregulation of superoxide dismutase activity in CG-injected mice. CONCLUSIONS: Acatalasemia, therefore, exacerbates oxidant tissue injury and induces the peritoneum to develop irreversible fibrosis which is the most important complication of peritoneal dialysis. This study suggests that catalase plays a crucial role in the defense against oxidant-mediated peritoneal injury in a mouse peritoneal fibrosis model.

Glycated albumin levels predict long-term survival in diabetic patients undergoing haemodialysis.

AIM: Glycated albumin (GA) is recognized as a reliable marker for monitoring glycemic control particularly in patients with end-stage renal disease (ESRD). Here, we investigated the impact of GA levels on long-term survival in diabetic patients with ESRD. METHODS: We enrolled ESRD patients with diabetic nephropathy into our single-centre prospective follow-up study (n = 98, 66 men and 32 women; age 68.2 12.3 years) with a mean follow-up period of 47.7 months. All patients had started haemodialysis between December 1992 and November 2003. They were categorized into two groups according to their GA levels at the initiation of haemodialysis; GA < 29% (low-GA group; n = 54) and GA 29% (high-GA group; n = 44). RESULTS: Between low-GA and high-GA groups, there were no significant differences in various clinical parameters except GA and HbA1c levels. The cumulative survival rate of low-GA group was significantly higher than that of high-GA group (P = 0.034, log-rank test). After adjustment for age, sex, total cholesterol, C-reactive protein and albumin, high-GA was a significant predictor of survival (hazard ratio 1.042 per 1.0% increment of GA, 95% CI 1.014-1.070, P < 0.05), but not in the case with HbA1c. Cox proportional hazard model demonstrated that high-GA group was a significant predictor for cardiovascular death (hazard ratio 2.971 (1.064-8.298), P = 0.038). CONCLUSION: We conclude that poor glycemic control (GA 29%) before starting haemodialysis is associated with increased cardiovascular morbidity and shortened survival in diabetic patients with ESRD.

Antithyroid drug-associated MPO-ANCA-positive tubulointerstitial nephritis in a type 2 diabetes patient: a case report.

A 54-year-old man diagnosed with type 2 diabetes and hyperthyroidism was prescribed propylthiouracil (PTU) after the patient developed hepatic dysfunction on thiamazole. At 50 mg/day of PTU, he was stable with thyroid-stimulating hormone receptor and thyrotropic antibody titers remaining stable. After four years of taking PTU, he was referred to the Department of Nephrology due to a rapid increase in his serum creatinine (Cr) level. He showed impaired renal function (Cr 2.26 mg/dL; estimated glomerular filtration rate (eGFR), 25 mL/min). In addition, urinary ß2-microglobulin (ß2 MG) was increased to 71,980 µg/L and was positive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) (33.9 U/mL). Gallium scintigraphy demonstrated a remarkable accumulation in both kidneys. The patient was diagnosed with tubulointerstitial nephritis based on a renal biopsy, the results of which suggested that it might have been induced by PTU. He was treated with prednisolone (PSL) at 30 mg/day. As a result, within two weeks, Cr, eGFR, and urinary ß2 MG levels were progressively improved to 1.72 mg/dL, 34 mL/min, and 22,020 µg/L, respectively. Therefore, we tapered off the PSL with a dose of 5 mg/day after approximately one year. There have been no exacerbated renal function parameters. Although there are many reports on patients developing MPO-ANCA-positive crescentic glomerulonephritis after the administration of PTU, we report on a relatively rare case in which interstitial nephritis occurred after the administration of PTU.

Perturbation of autocrine/paracrine loops of burst-forming units of erythroid-derived cells in rHuEPO-hyporesponsive hemodialysis patients.

BACKGROUND: Quantitative or qualitative abnormalities of erythroid progenitors in patients with chronic renal failure (CRF) could be the major factor for recombinant human erythropoietin (rHuEPO) hyporesponsiveness and severe anemia in hemodialysis (HD) patients receiving rHuEPO therapy. METHODS: Purified 1 x 10(4) circulating CD34+ cells isolated from rHuEPO-hyporesponsive HD patients (EPO-H; n = 10), rHuEPO-responsive non-HD patients with CRF (EPO-R; n = 8), nonanemic HD patients without rHuEPO therapy (EPO-W/O; n = 10), and healthy volunteer controls (CON; n = 10) were subjected to a methylcellulose culture system supplemented with rHuEPO, recombinant human interleukin-3 (IL-3), recombinant human stem cell factor (SCF), and recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) for 14 days. RESULTS: The average number of burst-forming units of erythroids (BFU-Es) was significantly less in the EPO-H group compared with the CON and EPO-W/O groups. Furthermore, colony size also was significantly smaller in the EPO-H group. Total RNAs were extracted from approximately 100 colonies/patient and subjected to complementary DNA expression array studies of 268 growth factors, cytokines, chemokines, and their receptors. A characteristic cluster upregulated in the EPO-R and EPO-W/O groups and downregulated in the EPO-H group was identified that contained various cytokines and growth factors, including IL-6, GM-CSF, vascular endothelial growth factor B, IL-9, IL-3, leukemia inhibitory factor, and interferon alpha-2, and such receptors as thrombopoietin receptor, IL-9 receptor, and colony-stimulating factor 1 receptor. CONCLUSION: These data suggest that the cross-talk network or autocrine/paracrine regulatory loop is critically impaired in BFU-E-derived cells in EPO-H patients, and investigation of these cluster genes would facilitate the development of novel therapeutic strategies for such patients.

Intravenous vitamin D therapy reduces PTH-(1-84)/large C fragments ratio in chronic hemodialysis patients.

BACKGROUND: Renal osteodystrophy is one of the major complications in patients with chronic renal failure. Large C-PTH fragments are secreted from the parathyroid glands and exert antagonistic actions against PTH-(1-84). The PTH-(1-84)/large C-PTH fragments ratio reflects both biosynthesis and processing of PTH; however the alteration of the ratio under vitamin D therapy has not been investigated. METHODS: Seventeen hemodialysis patients with intact PTH levels of >300 pg/ml were enrolled. Calcitriol or maxacalcitol were administered intravenously for 78 weeks. Intact PTH, PTH-(1-84), and the PTH-(1-84)/large C-PTH fragments ratio were measured at 0, 13, 26, 52 and 78 weeks. RESULTS: Intact PTH and PTH-(1-84) levels, which were 492.0 +/- 115.7 and 303.4 +/- 105.4 pg/ml, respectively, at baseline, significantly decreased at the end of the study to 268.9 +/- 121.9 (p < 0.0001) and 190.7 +/- 106.9 pg/ml (p = 0.0008), respectively. In contrast, large C-PTH fragments, which were 152.7 +/- 53.5 pg/ml at baseline, did not significantly change at 78 weeks (144.5 +/- 72.2 pg/ml, p = 0.7612). Consequently, the PTH-(1-84)/large C-PTH fragments ratio was significantly reduced from 2.25 +/- 1.31 to 1.47 +/- 0.89 (p = 0.0004). CONCLUSION: The PTH-(1-84)/large C-PTH fragments ratio reflects the change of PTH biosynthesis, processing and secretion from the parathyroid glands, and it may be a beneficial marker to evaluate the overall biological PTH action and predict bone turnover status in hemodialysis patients under intravenous vitamin D therapy.

Long-term effect of cinacalcet hydrochloride on abdominal aortic calcification in patients on hemodialysis with secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is one of the common complications in dialysis patients, and is associated with increased risk of vascular calcification. The effects of cinacalcet hydrochloride treatment on bone and mineral metabolism have been previously reported, but the benefit of cinacalcet on vascular calcification remains uncertain. The aim of this study was to evaluate the impact of cinacalcet on abdominal aortic calcification in dialysis patients. SUBJECTS AND METHODS: Patients were on maintenance hemodialysis with insufficiently controlled SHPT (intact parathyroid hormone [PTH] >180 pg/mL) by conventional therapies. All subjects were initially administered 25 mg cinacalcet daily, with concomitant use of calcitriol analogs. Abdominal aortic calcification was annually evaluated by calculating aortic calcification area index (ACAI) using multidetector computed tomography (MDCT), from 12 months before to 36 months after the initiation of cinacalcet therapy. RESULTS: Twenty-three patients were analyzed in this study. The mean age was 59.0±8.7 years, 34.8% were women, and the mean dialysis duration was 163.0±76.0 months. After administration of cinacalcet, serum levels of intact PTH, phosphorus, and calcium significantly decreased, and mean Ca × P values significantly decreased from 67.4±7.9 mg(2)/dL(2) to 52±7.7 mg(2)/dL(2). Although the ACAI value did not decrease during the observation period, the increase in ACAI between 24 months and 36 months after cinacalcet administration was significantly suppressed. CONCLUSION: Long-term administration of cinacalcet was associated with reduced progression of abdominal aortic calcification, and achieving appropriate calcium and phosphorus levels may reduce the rates of cardiovascular events and mortality in patients on hemodialysis.

Randomized controlled open-label trial of vitamin E-bonded polysulfone dialyzer and erythropoiesis-stimulating agent response.

BACKGROUND AND OBJECTIVES: A 1-year multicenter prospective randomized controlled study was conducted on the effects of vitamin E-bonded polysulfone dialyzers on erythropoiesis-stimulating agent response in hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Major inclusion criteria were use of high-flux polysulfone dialyzers with 50-70 ml/min ß2-microglobulin clearance over 3 months, transferrin saturation over 20%, same erythropoiesis-stimulating agent for over 3 months, and hemoglobin at 10-12 g/dl. Hemodialysis patients were placed in four interventional groups: two hemoglobin ranges (10.0-10.9 or 11.0-11.9 g/dl) and two dialyzers. Patients were randomly assigned by central registration to a vitamin E-bonded polysulfone dialyzers or polysulfone control group. Primary end point was relative erythropoiesis resistance index at baseline between groups at 12 months. Erythropoiesis resistance index was defined as total weekly erythropoiesis-stimulating agent dose divided by hemoglobin. RESULTS: There were no statistically significant differences in age or sex. There was no significant difference in relative erythropoiesis resistance index between vitamin E-bonded polysulfone dialyzers and control groups at 12 months (vitamin E-bonded polysulfone dialyzers: 1.1, control: 1.3). The vitamin E-bonded polysulfone dialyzers group showed better relative erythropoiesis resistance index than the control group at 11.0-11.9 g/dl hemoglobin (vitamin E-bonded polysulfone dialyzers: 1.0, control: 1.4 at 12 months, significant difference) but no difference at 10.0-10.9 g/dl hemoglobin. CONCLUSIONS: The overall relative erythropoiesis resistance index showed no difference between the vitamin E-bonded polysulfone dialyzers and control groups, although the change in relative erythropoiesis resistance index differed according to hemoglobin level.

The therapeutic potential of synthetic human atrial natriuretic peptide in nephrotic syndrome: a randomized controlled trial.

BACKGROUND: In nephrotic syndrome, the combination of furosemide and albumin infusion is a standard regimen to treat systemic edema. The efficacy of synthetic human atrial natriuretic peptide (hANP) for nephrotic syndrome to ameliorate the systemic edema and retain renal functions has not been fully demonstrated. TRIAL DESIGN: We conducted a prospective, randomized, controlled, open-label clinical trial. Patients were randomly assigned by a stratified biased coin design. METHODS: A total of 12 patients with nephrotic syndrome between the ages of 20 to 79 years were enrolled and randomly assigned to either the conventional (CON) group treated with furosemide and albumin, and hANP group, in which carperitide was administered in addition to the conventional therapies. The primary end points were: (1) the differences in serum creatinine levels, and (2) the reduction of total dosage of furosemide and albumin by the treatments of hANP. Secondary end points were body weight, systolic blood pressure, heart rate, serum protein, albumin, and urinary protein excretion. RESULTS: A total of 13 patients were enrolled, and one patient was excluded due to severe pneumonia. In both hANP (n = 7) and CON (n = 5) groups, body weight was reduced after 2-week treatments. Serum creatinine levels at follow-up significantly increased compared with baseline. The increase in serum creatinine levels (Δ serum creatinine) was smaller in the hANP group compared with the CON group (P = 0.31). The serum uric acid, serum urea nitrogen, and urinary protein excretion were reduced in the hANP group, and increased in the CON group, though these differences were not statistically significant. The usage of hANP significantly reduced the total dosage of furosemide (P < 0.05) during the treatment periods. No adverse effects were observed. CONCLUSIONS: The concomitant use of synthetic hANP with conventional therapies is beneficial for reducing the dosage of loop diuretics, and the elevation of serum creatinine and uric acid may be avoided.

Effluent free radicals are associated with residual renal function and predict technique failure in peritoneal dialysis patients.

OBJECTIVE: Residual renal function (RRF) is associated with low oxidative stress in peritoneal dialysis (PD). In the present study, we investigated the relationship between the impact of oxidative stress on RRF and patient outcomes during PD. METHODS: Levels of free radicals (FRs) in effluent from the overnight dwell in 45 outpatients were determined by electron spin resonance spectrometry. The FR levels, clinical parameters, and the level of 8-hydroxy-2'-deoxyguanosine were evaluated at study start. The effects of effluent FR level on technique and patient survival were analyzed in a prospective cohort followed for 24 months. RESULTS: Levels of effluent FRs showed significant negative correlations with daily urine volume and residual renal Kt/V, and positive correlations with plasma ß(2)-microglobulin and effluent 8-hydroxy-2'-deoxyguanosine. A highly significant difference in technique survival (p < 0.05), but not patient survival, was observed for patients grouped by effluent FR quartile. The effluent FR level was independently associated with technique failure after adjusting for patient age, history of cardiovascular disease, and presence of diabetes mellitus (p < 0.001). The level of effluent FRs was associated with death-censored technique failure in both univariate (p < 0.001) and multivariate (p < 0.01) hazard models. Compared with patients remaining on PD, those withdrawn from the modality had significantly higher levels of effluent FRs (p < 0.005). CONCLUSIONS: Elevated effluent FRs are associated with RRF and technique failure in stable PD patients. These findings highlight the importance of oxidative stress as an unfavorable prognostic factor in PD and emphasize that steps should be taken to minimize oxidative stress in these patients.

Icodextrin increases technique survival rate in peritoneal dialysis patients with diabetic nephropathy by improving body fluid management: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: There are still controversies whether peritoneal dialysis (PD) with icodextrin preserves residual renal and peritoneal membrane functions in patients with diabetes. However, there are no randomized controlled and long-term clinical trials in newly started PD patients with diabetic nephropathy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Forty-one patients with diabetic nephropathy with ESRD were enrolled and randomly assigned to the glucose group (GLU) treated with 8 L of 1.5% or 2.5% glucose or an icodextrin group (ICO) treated with 1.5 or 2.0 L of 7.5% icodextrin-containing solutions. Technique failure, body fluid management, glucose and lipid metabolism, and residual renal and peritoneal functions and were evaluated over 2 years. RESULTS: The technique survival rate was 71.4% in ICO and 45.0% in GLU, with most of the technique failure due to volume overload. ICO showed significantly better cumulative technique survival. Net ultrafiltration volume was significantly higher in ICO throughout the study period. There were no beneficial effects of icodextrin on hemoglobin A1c, glycoalbumin, and lipid profile at 24 months. Urine volume and residual renal function declined faster in ICO, but there were no significant differences between the two groups. For peritoneal function, no differences were observed in dialysis-to-plasma creatinine ratios during the observation. CONCLUSIONS: In PD therapy for diabetic nephropathy, the use of icodextrin-containing solutions has a beneficial effect on technique survival, but there are no apparent benefits or disadvantages in residual renal and peritoneal functions compared with conventional PD with glucose solution.

Long-term use of vitamin E-coated polysulfone membrane reduces oxidative stress markers in haemodialysis patients.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and an independent predictor of overall mortality and cardiovascular outcome in haemodialysis (HD) patients. In the present study, we compared the effects of a vitamin E-coated polysulfone membrane (PSE) and a non-vitamin E-coated polysulfone membrane (PS) on oxidative stress markers such as ADMA. METHODS: Thirty-one HD patients were enrolled to this investigation. They were allocated into two groups: in the PSE group (n = 16), PSE was used for 6 months, followed by PS for an additional 12 months; in the PS group (n = 15), PS was used for the entire observation period. Plasma ADMA, oxidized low density lipoprotein (Ox-LDL) and malondialdehyde LDL (MDA-LDL) levels were measured at baseline, 3, 6, 12 and 18 months. Plasma ADMA in peritoneal dialysis (PD) patients and in healthy individuals was also measured. RESULTS: Predialysis concentrations of ADMA (0.72+/- 0.13 nmol/ml) were significantly higher in the HD group than in both PD patients (0.63+/-0.10 nmol/ml, P<0.01) and healthy individuals (0.44+/-0.01 nmol/ml, P<0.0001). Treatment with PSE for 6 months significantly reduced predialysis levels of ADMA (0.54+/-0.09 nmol/ml) compared with baseline (0.74+/-0.12 nmol/ml; P<0.01). Predialysis levels of Ox-LDL and MDA-LDL after 6 months therapy with PSE were also significantly lower than baseline values. Treatment with PS subsequent to treatment with PSE again increased ADMA, Ox-LDL and MDA-LDL back to baseline levels. In the PS group, ADMA, Ox-LDL and MDA-LDL levels remained unchanged during the entire treatment period of 18 months. CONCLUSIONS: We confirmed that use of PSE reduced ADMA that had accumulated in HD patients. This finding indicates that PSE exerts anti-oxidant activity. A randomized controlled study will be required to determine whether PSE prevents cardiovascular diseases and other dialysis-related complications by reducing oxidative stress.

Elevated serum interleukin-18 levels might reflect the high risk of hospitalization in patients on peritoneal dialysis.

BACKGROUND: Interleukin (IL)-18 is a potent pro-inflammatory cytokine and plays a central role in atherosclerotic plaque rupture and accelerates atherosclerosis. AIM: The aim of this study was to determine serum IL-18 levels in patients on peritoneal dialysis (PD) and to assess their relationship with hospitalization. METHODS: Forty-three PD patients and 20 healthy individuals were enrolled in this study. We investigated the relationship of the serum concentrations of IL-18 and other well-established atherosclerotic markers, such as asymmetric dimethylarginine (ADMA). Hospitalization data from over a 18-month period were prospectively obtained on all 43 PD patients. Classic factors were entered into a Cox regression model to predict first hospitalization. RESULTS: The serum levels of IL-18 in patients on PD were significantly higher than those of healthy individuals (228.5 +/- 140.3 pg/mL vs 154.8 +/- 44.7 pg/mL, P < 0.05, respectively). Furthermore, serum IL-18 levels showed a positive correlation with duration of PD, serum beta2 microglobulin and serum ADMA levels. Mean serum levels of IL-18 were significantly higher among patients who had experienced at least one hospitalization than those who had not (279.9 +/- 164.3 vs 158.5 +/- 43.9 pg/mL, P = 0.0426). Furthermore, the relative risk for first hospitalization for each increase in IL-18 (pg/mL) levels was associated with a 1.182 (95% confidence interval, 1.012-1.364; P = 0.0071) increase in the risk for future hospitalization events. CONCLUSION: The present study suggests the elevated serum IL-18 levels might increase the risk for future hospitalization in patients on PD.

Plasma neuropeptide Y concentrations in patients on hemodialysis.

BACKGROUND: Neuropeptide Y (NPY) is a 36-amino-acid peptide that was originally isolated from the porcine brain. NPY, in contrast to leptin, is one of the most potent appetite stimulants. In some previous studies, NPY was found to be correlated with mean blood pressure (MBP) and fluid volume in patients on hemodialysis (HD), contributing to volume-induced hypertension. However, it is still unclear which NPY-sensitive neuronal pathways are responsible for the various changes seen in response to central NPY administration. In this study we analyzed the correlation of circulating levels of NPY with parameters of nutritional conditions, and we investigated the relationships between NPY concentrations and clinical markers of fluid volume in patients on HD. We also evaluated the effects of high-flux dialysis membranes on plasma NPY levels as compared with those of low-flux membrane. METHODS: Plasma NPY concentrations in patients on regular HD were measured using commercially available radioimmunoassay (RIA) kits. We examined the relationship between plasma NPY concentration and other clinical indices in patients on HD. RESULTS: Plasma NPY concentrations were inversely correlated with the serum urea nitrogen levels (r = -0.32) as well as protein catabolic rate (PCR) (r = -0.28). Plasma NPY was also correlated with the increase in body weight between HD sessions (r = 0.29). On the other hand, plasma NPY concentrations were not correlated with MBP, atrial natriuretic peptide (ANP), or adrenomedullin (AM). The reduction rate of plasma NPY with a high-flux dialysis membrane was significantly higher than that with a low-flux dialysis membrane. CONCLUSIONS: The secretion of NPY may be enhanced in a poor state of nourishment and stress induced by fluid volume overload in patients on HD, and plasma NPY is removed by a high-flux dialyzer.

Serum levels of soluble CD26 and CD30 in patients on hemodialysis.

BACKGROUND/AIMS: Various abnormalities of the immune system have been demonstrated in patients on hemodialysis (HD). We hypothesize that the imbalance between type 1 helper T (Th1) cells and type 2 helper T (Th2) cells in patients on HD contributes to these abnormalities. Furthermore, we investigate the relationship between the Th1/Th2 imbalance and HD duration. METHODS: We measured the serum levels of soluble CD26 (sCD26) and soluble CD30 (sCD30) in 47 patients on HD and in 13 patients with chronic renal failure not on HD and analyzed the effect of HD duration on the serum levels of sCD26 and sCD30. RESULTS: The serum level of sCD26 in the HD group was significantly lower than that in the control group. On the other hand, the serum levels of sCD30 in the HD group and in the CRF group were significantly higher than in the control group. In the short-term HD group (<1 year), the serum levels of sCD26 were lower and the sCD30 levels higher than those in middle-term HD group (1-10 years). CONCLUSIONS: In the HD group, the Th1/Th2 balance may shift towards Th2 dominance. It is possible that this imbalance contributes to the abnormality of the immune system in HD patients.

The critical role of SRC homology domain 2-containing tyrosine phosphatase-1 in recombinant human erythropoietin hyporesponsive anemia in chronic hemodialysis patients.

The molecular mechanism of anemia that is hyporesponsive to recombinant human erythropoietin (rHuEPO) in hemodialysis patients without underlying causative factors has not been investigated fully in hematopoietic stem cell system. Circulating CD34+ cells (1 x 10(4)) were isolated from rHuEPO hyporesponsive hemodialysis patients (EPO-H; n = 9), patients who were responsive to rHuEPO (EPO-R; n = 9), and healthy control subjects (n = 9). The patients with known causes of EPO hyporesponsiveness were eliminated from the current study. The cells were cultured in STEM PRO 34 liquid medium, supplemented with rHuEPO, IL-3, stem cell factor, and granulocyte-macrophage colony stimulating factor for 7 d and then transferred to a semisolid methylcellulose culture medium for performing burst forming unit-erythroid (BFU-E) colony assay. Expression of src homology domain 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 5 (p-STAT5) was assessed with Western blot analysis. In EPO-H patients, SHP-1 antisense or scrambled S-oligos were included in the culture medium, and its effects were evaluated. The number of circulating CD34+ cells was not statistically different among the three groups, and their proliferation rates were similar for 7 d in culture. However, BFU-E colonies were significantly decreased in EPO-H patients compared with EPO-R and control groups. The mRNA and protein expression of SHP-1 and p-SHP-1 was significantly increased, whereas that of p-STAT5 was reduced in EPO-H patients. The inclusion of SHP-1 antisense S-oligo in culture suppressed SHP-1 protein expression associated with p-STAT5 upregulation, increase in p-STAT5-regulated genes, and partial recovery of BFU-E colonies. In EPO-H hemodialysis patients, the EPO signaling pathway is attenuated as a result of dephosphorylation of STAT5 via upregulation of SHP-1 phosphatase activity, and SHP-1 may be a novel target molecule to sensitize EPO action in these patients.