Morphological changes in the tubulointerstitial compartment in primary glomerulopathies

The renal interstitium structurally supports the functional renal units and is involved in almost all renal functions. The degree of renal disfunction strongly correlates to the changes in the tubulointerstitial compartment present in almost all types of glomerular diseases. A phenomenon arising in such an environment is epithelial-mesenchymal transition, i.e. a change of the cell;s epithelial phenotype into a mesenchymal one. Histochemical, immunohistochemical and morphometric analyses were made of 50 renal biopsies with primary glomerulopathies, as well as light-microscopy analyses of semi-thin sections embedded in epoxy resin. Double immunohistochemical stainings with pairs of epithelial and mesenchymal antibodies were also done. The results were analyzed and correlated with the clinical data of the renal function of the patients. The immunohistochemical analyses of the atrophic tubular epithelial cells showed a loss of expression of Cytokeratin and E-cadherin, an enhanced expression of HLA-DRalpha, and a de novo expression of Vimentin and alphaSMA as markers for epithelial-mesenchymal transition. The double immunohistochemical stainings with Cytokeratin/Vimentin and Cytokeratin/alphaSMA showed a simultaneous expression of these antigens in atrophic tubular cells. Their proliferative index was mildly enhanced. Interstitial fibrosis was present in 98% of the analysed biopsies. The analyses show correlations among all the changes in the tubulointerstitial compartment as well as the concentration of creatinine in the serum as a parameter of renal function. The study emphasizes the usefulness of the implementation of histomorphometrical and immunohistochemical techniques as well as ultrastructural and molecular analyses in the process of nephropathological diagnosis.