chondroitin-sulfates and Nephrotic-Syndrome

Lymphocytes are involved in the physiopathologic mechanism of idiopathic nephrotic syndrome (INS). We have recently demonstrated that plasma from patients with INS decreases human glomerular epithelial cell (GEC) glycosaminoglycans (GAGs), particularly heparan sulfates (HS) in vitro. In this study we investigate the effect of peripheral blood lymphocytes (PBL) from INS patients on glomerular cell GAG and HS.. Human GECs were cultured with total peripheral blood mononuclear cells (PBMCs), PBL, and monocytes from patients and controls. The amounts of GAG and HS were assessed using a cationic membrane after metabolic labeling.. In coculture with GECs, mononuclear cells from controls decreased total epithelial cell GAG (-30% with PBMC, P < 0.05; -25% with PBL, P < 0.02; -19% with monocytes, P < 0.05). Particularly HSs were decreased (-36% with PBMC, P < 0.05; -27% with PBL, P < 0.02; and -19% with monocytes, P < 0.05). When GECs were in coculture with PBL from INS patients, the decrease in GAG and HS was significantly greater in comparison to control PBL (-10%, P < 0.02; -10%, P < 0.02, respectively, for GAG and HS). Moreover, supernatants of stimulated PBMCs from patients decreased also GAG and HS in comparison with controls (-13%, P < 0.02; -15%, P < 0.02, respectively, for GAG and HS).. These data provide direct evidence that PBLs from INS patients are able to decrease GEC HS as previously shown with plasma from patients. This might be instrumental in the onset of albuminuria.

Topics: Cells, Cultured; Child; Chondroitin Sulfates; Glycosaminoglycans; Heparitin Sulfate; Humans; Kidney Glomerulus; Lymphocytes; Monocytes; Nephrotic Syndrome; Polymers; Reference Values

Danaparoid sodium is an antithrombin composed of 3 glycosaminoglycans: heparan sulfate, dermatan sulfate and chondroitin sulfate. Similar to heparin, danaparoid operates by activating antithrombin 3, but does not contain heparin or heparin fragments, and is therefore antigenically distinct. Danaparoid has been advocated as a safe and effective anticoagulant for heparin-associated thrombocytopenia. However, there is little experience in its use as a substitute for heparin in hemodialysis. We report 2 men, aged 82 and 73 years, respectively, who developed thrombocytopenia while undergoing hemodialysis with heparin, and who subsequently underwent successful dialysis with danaparoid. There was a rise in platelet levels in both while receiving danaparoid, and dialysis was completed without hemorrhagic or thrombotic complications. Danaparoid is a safe and effective substitute for heparin, and may be used as an anticoagulant in hemodialysis.

Topics: Aged; Aged, 80 and over; Antithrombin III; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Male; Nephrotic Syndrome; Platelet Aggregation; Renal Dialysis; Thrombocytopenia

To evaluate the specificity of a raised heparan sulphate (HS) excretion previously reported in four children with congenital nephrotic syndrome (CNS), we measured the urinary excretion of HS and chondroitin sulphate (CS) in seven children with Finnish-type congenital nephrotic syndrome (CNSF), seven with diffuse mesangial sclerosis (DMS), nine with focal segmental glomerulosclerosis (FSGS), 14 with steroid-sensitive nephrotic syndrome of whom eight had a biopsy confirming minimal change histology (SSNS), and 17 controls. The urine HS/CS ratio in normal children had a median of 0.36 (observed range 0.21 to 0.68) and was independent of age. HS/CS ratio was significantly greater than controls in CNSF (median 0.80, range 0.43 to 1.28), DMS (median 0.81, range 0.49 to 1.13) and FSGS children (median 0.66, range 0.38 to 1.6), but was not in SSNS (median 0.44, range 0.28 to 0.70). There was a positive correlation between the HS/CS ratio and urine albumin excretion. High HS/CS ratios are not diagnostic of a particular histological variety of CNS.

Topics: Albuminuria; Child; Child, Preschool; Chondroitin Sulfates; Creatinine; Female; Glomerulosclerosis, Focal Segmental; Glycosaminoglycans; Heparitin Sulfate; Humans; Infant; Male; Nephrosis, Lipoid; Nephrotic Syndrome; Steroids

Topics: Child; Chondroitin Sulfates; Diabetes Mellitus; Glomerulonephritis; Glycosaminoglycans; Heparitin Sulfate; Humans; Mucopolysaccharidoses; Nephritis, Hereditary; Nephrotic Syndrome; Proteinuria

Previously we found that alpha 2-acid glycoprotein fraction from urine of patients with the nephrotic syndrome stimulated the lipoprotein lipase reaction in vivo and in vitro. The activator was separated from the alpha 1-acid glycoprotein and identified as a glycosaminoglycan. The studies reported here were undertaken to characterize and quantify the glycosaminoglycans contained in urine of patients with the nephrotic syndrome and to compare these to the glycosaminoglycans in urine of the control subjects. We found that free low molecular weight glycosaminoglycans, heparan sulfate and chondroitin 4-sulfate, are excreted in both patients with the nephrotic syndrome and controls however, patients with the nephrotic syndrome excreted much less of both glycosaminoglycans. The free form of heparan sulfate was found to be the activator which stimulated the lipoprotein lipase reaction in vitro in the presence of apolipoprotein CII. In addition, the urine from patients with the nephrotic syndrome contained a protein-glycosaminoglycan complex which was absent in control urine. Glycosaminoglycans in the complex could be released by papain digestion or by trichloroacetic acid. Our evidence indicates that this glycosaminoglycans fraction is a law charge form of chondroitin sulfate.

Topics: Chondroitin Sulfates; Enzyme Activation; Glycosaminoglycans; Heparitin Sulfate; Humans; Lipoprotein Lipase; Molecular Weight; Nephrotic Syndrome