The pathogenesis of dialysis related amyloidosis, which occurs preferentially in osteo articular tissues, is still incom pletely understood. Although recent histological studies have shown the accumulation of monocytes/macrophages around amyloid deposits, the factor(s) causing their infiltration and pathological involvement have yet to be fully elucidated. The present studies demonstrate that ? 2 microglobulin (? 2 m), the major constituent protein in amyloid fibrils, can be modified in situ by advanced glycation end products (AGE) through binding to AGE modified collagen. AGE ? 2 m attracts monocytes via direct chemotaxis and through regulation of synoviocyte derived chemokine. AGE modified ? 2 m significantly delays spontaneous apoptosis of human monocytes via a pathway mediated by the receptor for AGE (RAGE), processes which may increase the accumulation of inflammatory monocytes. In addition to recruit monocytes, AGE ? 2 m stimulates macrophages to release IL 1?, TNF ? and IL 6.These proinflammatory cytokines upregulate the expression of adhesion molecules such as ICAM 1 and VCAM 1 by synovial cells and induce the release of synoviocyte derived collagenase which may contribute to the degradation of matrix. These AGE ? 2 m induced perturbation of monocytes and cellular inflammatory reactions eventually result in osteo articular tissue damage and destruction seen in DRA.

Infection is a common, serious and costly complication in patients with chronic renal failure (CRF) and has been the major cause of high mortality in these patients. Increased evidences suggest that prophylaxis can significantly decrease the prevalence of infections in CRF patients, such as tuberculosis, S. aureus infection and hepatitis virus induced liver diseases. It remains an important issue for clinical nephrologists to investigate and to provide strategies for prevention and treatment of various infections in CRF patients.

To elucidate the role of reactive carbonyl compounds in the pathogenesis of vascular complication in patients with chronic renal failure or diabetes. Vascular endothelial cells (VECs) were isolated from human umbilical vein and cultured with 3-deoxyglucosone (3-DG) or methylglyoxal(MGO) in vitro. Expression of ICAM-1 and VCAM-1 on the surface of VECs was detected by flow cytometer. The results showed that up-regulation of expression of ICAM-1 and VCAM-1 was observed when either 3-DG or MGO was added into the cultures, which was inhibited by a carbonyl compounds scavanger, aminoguanidine. These data suggested that accumulation of reactive carbonyl compounds in patients with chronic renal failure or diabetes might be involved in the mechanism of arteriosclerosis.

Objective: Enhanced expression of adhesion molecules on synovial tissu e has been demonstrated in patients with dialysis-related amyloidosis (DRA). T he study was conducted to elucidate the mechanisms by which the expression of adh esion molecules on synovial cells was up-regulated.Methods: Human type-B synov ial cells were cultured in vitro with β2-microglobulin modified with adva nced glycation end products (AGE-β2m) , native β2-microglobulin (β2 m) , tumor necrosis factor-α（TNF-α）and interleukin -1β（ IL-1β）. The expression of intercellular adhesion molecule-1(ICAM-1), vasc ular cell adhesion molecule-1(VCAM-1), and E-selectin was examined by immunofluor esc enct staining and flow cytometer analysis. Results:ICAM-1 and VCAM-1, but not E -selectin, were constitutively expressed on human type-B synovial cells. TNF -α a nd IL-1β enhanced the expression of ICAM-1 and VCAM-1 in a dose- and time - depen dent manner. Neither of these cytokines appeared to induce the expression of E - selectin. Both β2m and AGE-β2m had no direct effect on the expression of the a dhesion molecules.Conclusion: Elevated level of IL-1β and TNF-α in the synov ial tissue may up-regulate the expression of adhesion molecules on synovial cel ls and therefore promote local monocytes infiltration.

To observe changes in oxidative stress and effects of dialysis on patients with end stage renal disease (ESRD), vitamin E, GSH, malondialdehyde (MDA) levels in plasma and carbonyl contents of plasma proteins, and blood glutathione peroxidase (GPx) activity were assayed in healthy individuals, chronic renal failure (CRF) patients before dialysis, and after hemodialysis (HD) or peritoneal dialysis (PD). As compare with healthy control, plasma levels of vitamin E and GPx activity of CRF patients were lower, whereas plasma contents of both MDA and carbonyl content of plasma proteins were increased significantly ( P

Objective The study was performed to determined the significance and safety of liver biopsies in these patients as a pre-transplantation screening test. Methods From January 1999 to August 2002, seventy-four renal transplant recipients with hepatitis B or C virus infection were received the percutaneous liver biopsy. The severity of liver inflammation(G) and fibrosis(S) were evaluated by semi-quantity technique. The patients whose liver histological diagnosis was G 0-2 S 0-2 received renal transplantation(n=31). Patients with hepatitis B or C virus infection who received renal transplantation in the period of January 1995 to December 1998 were selected as historic controls. Normal level of serum transaminase was considered as a indication for the received renal transplantation during this period. The incidence of liver dysfunction after transplantation was compared between the two groups. Results It showed among thirty-one patients received renal transplantation from 1999-2002, only 1 patient (3.2%) developed liver failure after transplantation. However, among 60 patients of historic control, 17 (23.8%) suffered from liver dysfunction (P

Objective To investigate the effect of vitamin E supplementation on oxidative stress in hemodialysis patients. Methods Fifty-six uremic patients undergoing hemodialysis (HD) were involved in this self-controlled study. The patients were observed for one month to evaluate the status of oxidative stress and then divided into two groups randomly. Group A patients (n=28) received 200mg/d of vitamin E and Group B patients (n=28) were treated with 400mg/d of vitamin E. Vitamin E was supplied for one month in both groups. The serum levels of advanced oxidation protein products (AOPP), malondialdehyde (MDA), vitamin E and activity of glutathione peroxidase (GSHPx) were measured at the initial and the end of vitamin E supplementation respectively. Results Serum levels of AOPP and MDA were significantly higher in HD patients compared with healthy controls (n=56, P

Objective A close relationship between atherosclerosis and plasma levels of advanced oxidation protein products (AOPP) has been demonstrated in patients with chronic renal failure. The present study was performed to investigate the effect of AOPP on human endothelial cells. Methods Human umbilical vein endothelial cell line ECV304 was incubated with different concentrations of AOPP-BSA, which prepared by combining BSA with HOCl at different molar ratios. Cell viability was measured by MTT assay. Intracellular production of reactive oxygen species (ROS) was evaluated kinetically using VICTOR Wallac 1420 mutilabel counter. Results AOPP-BSA decreased endothelial cell viability, which was dependent on the molar ratio of BSA/HOCl and the concentration of AOPP-BSA. AOPP-BSA also enhanced the intracellular ROS production in ECV304. AOPP-induced ROS production was correlated with the molar ratio of BSA/HOCl and the concentration of AOPP-BSA. Pretreatment of cells with a small molecular glutathione peroxidase mimic (ebselen) reduced AOPP-induced ROS production by 53% with preservation of cell viability. Conclusion AOPP decreased endothelial cell viability via induction of oxidative stress.

Objective To investigate the cellular receptor pathway and the intracellular signaling of advanced glycation end products(AGE)-induced inflammatory reaction in monocytes. Methods Human peripheral monocytes were isolated from healthy volunteers. Cells were incubated with AGE modified by the addition of human serum albumin (AGE-HSA) either with pretreatment or no pretreatment of anti-AGE receptor (RAGE) IgG, NADPH oxidase inhibitor (apocynin)or a specific inhibitor of p38(SB 203580). The levels of interleukin-1?(IL-1?)and tumor necrosis factor-?(TNF-?) in the supernatants were assayed with enzyme-linked immunoadsorbent assay (ELISA). Reactive oxygen species (ROS) production was determined by MCLA chemiluminescence. Nuclear factor-?B translocation was assayed by immunochemical staining with anti-NF-?B/p65 and electrophoretic mobility shift assay(EMSA). Results AGE-HSA was found to induce activation of NF-?B, increase levels of IL-1? and TNF-? in the supernatants, and enhance production of ROS by monocytes. Pre-treatment of cells with anti-RAGE IgG or apocynin inhibited AGE-HSA to induce NF-?B translocation and IL-1? or TNF-? production. AGE stimulated ROS production could also be blocked by pre-treatment of cultured cells with anti-RAGE IgG or apocynin. Pre-treatment of cultured cells with SB 203580 inhibited both NF-?B activation and cytokines production, but showed no significant effect the cells to produce ROS. Conclusion AGE-HSA could induce IL-1? and TNF-? release as well as ROS production in human monocytes via a pathway mediated by RAGE. Activation of NADPH oxidase may be the upstream of the intracellular pathway. AGE-induced cytokines production was p38 pathway-dependent.

Objective To evaluate the relationship between NK cytotoxicity and anemia in uremia. Methods The effect of rHuEPO on natural killer (NK) cell cytotoxic activity was studied in 12 hemodialysis(HD) patients. Results The levels of hemoglobin (Hb) and NK cell activity were significantly lower in HID patients than that in healthy controls. After two months of the treatment with rHuEPO, the levels of Hb in these patients rose significantly with a parallel rise in NK cell activity. NK cell activity was not increased when they were incubated with rHuEOP but was increased with red blcxxl cells. Conclusion Improved NK cell cytotoxicity in HD patients after treatment with rHuEPO was achieved through the rise in R15C rather than through rHuEPO itself.