Molecular analysis of glomerular diseases in renal biopsies

Summary: The purpose of this study was to determine the pattern of gene expression of type IV collagen alpha chains in several chronic human glomerular diseases using micro dissected glomeruli and assessment of mRNA by competitive polymerase chain reaction (PCR). After showing that the level of a2 type IV collagen mRNA was elevated in sclerotic glomeruli isolated from nephrectomies, we undertook a preliminary cross-sectional study of type IV collagen alpha chain mRNA in renal biopsies in two of the leading causes of glomerulosclerosis: (i) diabetic nephropathy; and (ii) membranous glomerulopathy. We found that glomerular type IV collagen mRNA levels alterations were disease-specific. the relative levels of the individual α-chains of type IV collagen depended on the anatomic site of the glomerular lesions. the α-2IV/α-3IV collagen mRNA ratio was high in diabetes mellitus, but not in membranous glomerulopathy. These data, coupled with that obtained in experimental animals, suggest that a defective basement collagen synthesis is associated with progressive glomerular scarring. If these conclusions are verified in studies of repeat biopsies, the risk of progressive glomerulosclerosis in individual patients could be estimated, leading to the means to assess therapeutic responses.