Progression of glomerular diseases

The nature and slope of progression of glomerular diseases is the subject of considerable discussion. The use of renal biopsies has been accompanied by considerable improvement in the classification of glomerular disease. However, the clinical and histological tools available to assess prognosis in individual patients lack accuracy, especially in slowly progressive glomerular diseases such as diabetes mellitus. The development of molecular biology tools provides a new approach to the analysis of glomerulosclerosis. The accumulation of extracellular matrix in the glomerulus results from an exaggerated synthesis of collagens and other molecules forming the basement membranes, and is accompanied by an increase in the corresponding mRNAs. The measure of local glomerular gene activation can therefore provide a dynamic view of glomerular scarring. Utilizing a method combining microdissection of the glomeruli, reverse transcription in situ and a competitive polymerase-chain-reaction assay we were able to measure minute amounts of mRNAs in single mouse and human glomeruli. Both in mouse models and in human glomerulosclerosis we found upregulation of basement membrane collagen genes in the glomeruli. The increase appeared to be parallel to the slope of progression of glomerulosclerosis in experimental animals. This new approach may therefore provide a quantitative and sensitive method to define the propensity to sclerosis in human disease.