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.

Objective To elucidate the clinical characteristics and the outcome of acute renal failure (ARF) in the elderly. Methods Clinical data of 109 elderly patients(≥60 years) with ARF were analysed and compared with that of 175 younger adult ARF patients(18 40 years) in the same period. Results 109 out of 422 patients(25 8%) with ARF were more than 60 years. The mortality rate of ARF in these patients was 58 7%. ARF was induced mainly by prerenal factors (20 2%) and sepsis (15 6%). Complications such as infections (52 3% vs 29 7%), cardiovascular events (64 2% vs 38 3%), respiratory failure (43 1% vs 20 0%) and hyperkalemia (29 4% vs 15 4%) were more prevalent in elderly patient than that in the younger adult ARF patients ( P

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.

The rats were fed on low salt diet for seven days,and then were randomly divided into five groups: control (n=7), CsA treated (n=7), CsA+Verapamil (n=7), CsA+Enalapril (n=7) and CsA+Losartan (n=7).CsA was given by subcutaneous injection (15mg?kg -1?d -1) for four weeks. The apoptosis of tubular and interstitial cells was detected by TUNEL assay. The proliferating cell nuclear antigen and Fas antigen expression were examined by immunohistochemical staining. Apoptosis of tubular and interstitial cells increased in CsA treated rats. CsA+Losartan and CsA+Enalapril treated rats had a statistically significant decrease in apoptosis when compared to CsA treated rats (7.3?1.1 and 6.6?0.8 vs 13.9?1.2 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.

Enhanced expression of adhesion molecules on human endothelial cells of synovial tissue has been demonstrated in patients with dialysis related amyloidosis(DRA).The study was conducted to elucidate the mechanism by which the expression of adhesion molecules on human endothelial cells was up regulated. Human endothelial cells derived from umbilical veins(HUVEC) were coincubated in vitro with native human serum albumin(HSA) or HSA modified with advanced glycation end products(AGE HSA).The expression of adhesion molecule intercellular adhesion molecule 1(ICAM 1),vascular cell adhesion molecule 1(VCAM 1) and E selectin was determined respectively by immunofluorescence staining and flow cytometer analysis.The results showed that ICAM 1 and VCAM 1, but not E selectin,were constitutively expressed on HUVEC. AGE HSA enhanced the expression of ICAM 1, VCAM 1 and E selectin on HUVEC in a time and dose dependent manner. HSA had no effect on the expression of adhesion molecules. The results led to the conclusion that AGE HSA up regulated the expression of adhesion molecules on human endothelial cells and therefore promoted the infiltration of monocytes/macrophages around ? 2 microglobulin amyloid.

Radioactive ligand receptor binding assay was used to study the binding effect of heparin and low molecular weight heparin (LMWH) on the receptor of advanced glycation end products (AGE) on monocyte surface in normal individual and chronic renal failure (CRF) patients undergoing hemodialysis. The results showed that heparin caused a dose dependent inhibition of receptor binding to AGE, however LMWH did not have such inhibitory effects. The results suggest that heparin could interrupt AGE clearance and degradation, and LMWH had not these effects.