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.

The aim of this study was to investigate the effect of patients isolation,paying careful attention to hygienic measure and strict sterilization on prevention of hepatitis C infection in hemodialysis(HD) unit. Patients in our HD unit from May 1994 to May 1998 were isolated and strict sterilization of dialysis apparatuses were performed, while patients from April 1990 to April 1994 were not isolated. The rate of HCV infection in these two groups of patients were 18 20% and 26 72%, respectively ( P

The study was performed to investigate the prevalence of nasal carriage of Staphylococcus aureus (NCSA) in patients with chronic renal failure(CRF) and its relationship with incidence of bacteremia in patients on hemodialysis(HD). The preventive effect of external application of mupirocin ointment on HD patients with venous catheters was also observed. Nasal swabs were taken from 114 CRF patients hospitalized from Nov. 2000 to April 2002. Samples from 42 patients in CCU with normal renal function and 48 staffs working in HD centre were also analyzed. External application of mupirocin ointment near the exit sites of catheters was performed as prophylaxis in HD patients with venous catheters. The prevalence of SA bacteremia was compared with that of the historical control group from Jan.1999 to Oct.2000. The results showed that the prevalence of NCSA in CRF patients was 14% (16/114). Nasal swab cultures were all negative in CCU patients, as well as staffs working in the HD centre. The mean frequency of SA bacteremia in HD patients with NCSA was 0 12/catheter month, compared to 0 in HD patients with no NCSA( P

The purpose of this study was to explore the incidence of tuberculosis (TB) in chronic renal failure (CRF) patients with or without renal replacement therapy and to evaluate the effect of chemoprophylaxis on incidence of active TB. A total of 3360 CRF patients from April 1989 to Sept. 2002 were enrolled in this study. Chemoprophylaxis for TB was given to the patients with increased serum anti PPD IgG levels from Jan. 1995 to Sept. 2002. The prevalence of active TB during this period was compared with that of the historical control group from April 1989 to Dec. 1998 (without prophylaxis). The results showed that the overall incidence of active TB in all patients was 2 4% (82/3360). Extrapulmonary TB was the most common feature (75 6%) with the major infective sites in pleura (20 7%) and lymph node (17 7%). There were 58 5% patients with active TB showing increased serum and/or serous exudate anti PPD IgG levels and 24 2% patients showing positive TB bacillus DNA (PCR). The total incidences of TB (1 76%) and disseminated TB (2 3%) in the chemoprophylaxis group were significantly lower than those in the non chemoprophylaxis group (4 1% and 7 5%, respectively, P

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.

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.

Objective To test the hypothesis that attachment of synovial cell to &?2-microglobulin modified with advanced glycation end products (ACE-?2m) would affect cell adhesion, spreading and proliferation.Methods Normal human synovial cells (type B cells) were isolated and plated in culture dishes coated with AGE-?2m or with normal extracellular matrix proteins (EMP). Adhesion was analyzed by counting the isotope-labelled cells. Spreading was tested using a light microscope and proliferation determined by 3H-TdR incorporation and counting the number of cells. Results Synovial cells adhered less effectively to AGE-?2m, ?2m and AGE-collagen than to the normal EMP (collagen and fibronectin). Cells interacting with AGE-?2m, ?2m or AGE-collagen also demonstrated less extensive spreading throughout the examined time intervals (60-120 minutes after plating), and decreased 3H-TdR incorporation and cell numbers after 72 hours of plating when compared to cells interacting with normal EMP. Conchusion AGE-?2m in amyloid may alter synovial cell behavior in situ in ways which cods contribute to the development of dialysis-related amyloidodsis(DRA).

Objective To determine the expression of advanced glycation end products(AGE) binding proteins on human joint synovial cells for elucidating the pathobiological effects of ?2m modified with AGE(AGE-?2m) on joint resident cells. Methods Type A and type B synovial cells were isolated and cultured in vitro. The expression of AGE receptor 1 (ACE-R1 ), AGE receptor 2 (AGE-R2), AGE receptor 3 (AGE-R3) and 35 KD receptor for AGE(RAGE) on synoviocytes were detected by immunofluorescent staining using specific antibodies and flow cytometric analyses. mRNA of AGE receptors was examined by RT-PCR techniques.-Results RAGE and AGE-R3, but not AGE-R1 and AGE-R2, were constitutively expressed on the membrane surface of both type A and type B synovial cells. These two types of synovial cell also expressed mRNA of RAGE and AGE-R3. Conclusion Human joint synovial cells express specific AGE binding proteins, RAGE and AGE-R3, suggesting that these cells may be involved in AGE metabolism and might be the target of the biological effects of AGEs in dialysis-related amyloidosis.