heparitin-sulfate and Nephrosis--Lipoid

We measured the concentrations of urine glycosaminoglycans (GAG) by the modified dimethylmethylene blue method and the concentration of urine heparan sulfate (HS) by enzyme-linked immunosorbent assay (ELISA) in patients with various glomerular diseases. The GAG/creatinine(Crea) ratios in patients with IgA nephropathy (mean +/- SD, 0.31 +/- 0.056) and membranous nephropathy (0.41 +/- 0.115) were significantly greater than in healthy controls (0.18 +/- 0.045). Urine GAG/Crea ratios in minimal change nephrotic patients increased during remission (0.38 +/- 0.102) and decreased to normal values during the nephrotic stage (0.25 +/- 0.088). In contrast, urine HS/Crea ratios in patients with minimal change nephrotic syndrome decreased during remission (0.0069 +/- 0.0029) and increased markedly during the nephrotic period (0.047 +/- 0.0007 versus controls 0.0158 +/- 0.0046). Serial measurement in three minimal change nephrotic patients showed the similar change for the HS/Crea ratio and urine albumin excretion in the course of steroid therapy. The loss of HS from the glomerular basement membrane (GBM) may therefore be related to the pathogenesis of increased albumin excretion and measurement of urine HS excretion may be helpful for studying metabolism in renal disease, especially in patients with minimal change lesions.

Topics: Adult; Enzyme-Linked Immunosorbent Assay; Female; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glycosaminoglycans; Heparitin Sulfate; Humans; Male; Methylene Blue; Nephrosis, Lipoid; Spectrophotometry; Urinalysis

We examined the effects of methylprednisolone (MPSL) on type IV collagen, laminin and heparan sulfate proteoglycan (HSPG) mRNA levels in the renal glomeruli and medulla of puromycin aminonucleoside (PAN) nephrosis. mRNA levels encoding for type IV collagen and laminin increased markedly, whereas those for HSPG decreased significantly in glomeruli of PAN nephrosis. Administration of MPSL partially ameliorated the abnormal gene expression for basement membrane components. Furthermore, we showed that medullary mRNA levels for all these basement membrane components decreased with age in PAN nephrosis with or without MPSL treatment, suggesting that neither PAN nor MPSL has any effect on basement membrane component mRNA levels in the renal medulla. In contrast, mRNA levels for the interstitial collagens including alpha 1 (I) and alpha 1 (III) chains in glomeruli showed little change with or without MPSL treatment, whereas those in medulla increased significantly in PAN nephrosis when compared with the control. MPSL ameliorated the abnormal gene expression of alpha 1 (I) and alpha 1 (III) collagen in renal medulla. These results indicate that PAN affects both glomerular mRNA encoding for basement membrane components and medullary mRNA encoding for interstitial collagens, and that MPSL has marked effects on the amelioration of abnormal gene expression in both glomeruli and medulla of PAN nephrosis.

Topics: Animals; Collagen; Extracellular Matrix Proteins; Gene Expression; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Kidney Glomerulus; Kidney Medulla; Laminin; Male; Methylprednisolone; Nephrosis, Lipoid; Proteoglycans; Puromycin Aminonucleoside; Rats; Rats, Inbred Strains; RNA, Messenger

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