Implications of tubulo-interstitial epithelial and mesenchymal relation in chronic kidney disease.

INTRODUCTION: Several studies have shown the prognostic value of markers detecting interstitial infiltration, epithelial-mesenchymal transition (EMT) and tubulo-interstitial damage in chronic kidney disease evolution. Aim of our investigation was to further evaluate the pathological correlation of such parameters in a population with chronic kidney disease in early stages. MATERIALS, METHODS AND RESULTS: In a population of 16 patients, with a prior diagnosis of chronic kidney disease in early stages, that underwent a biopsy procedure for clinical indication, there were evaluated the expression in kidney tissue of mesenchymal, epithelial and proliferation markers. Material remaining after routine light microscopy and immunofluorescence was stained for mesenchymal markers such as vimentin, epithelial markers such as cytokeratin and E-cadherin. Quantitative evaluation was conducted by electronic image analysis on consecutive low power fields, avoiding glomeruli, and estimated as percentage of the total area. The clinical and biochemical characteristics evaluated during the hospitalization period showed the prevalence of multiple cardiovascular risk factors such as: arterial hypertension (68%), abnormal blood lipid levels (32%), obesity (27%), diabetes (19%). The histopathological characteristics of chronic kidney dysfunction was related with higher expression of mesenchymal markers (p<0.001) and a decrease expression of epithelial markers (p=0.003). CONCLUSIONS: The interrelation of epithelial and mesenchymal tubulo-interstitial markers was demonstrated even in early stages of chronic kidney dysfunction.

Immunoexpression of alpha-SMA and CD68 in native kidney biopsies.

INTRODUCTION: The role for inflammation and fibrosis as predictive histopathological markers for renal function has been discussed in several studies. Aim of our investigation was to evaluate the clinico-pathological correlation of myofibroblasts expression as markers for initial development of fibrotic processes and macrophagic infiltration in a population with impaired renal function, in order to better understand their value in diagnostic biopsies. MATERIALS, METHODS AND RESULTS: We evaluated 20 consecutive native kidney biopsies performed for diagnostic purposes. Material remaining after routine light microscopy and immunofluorescence, was stained for α-SMA as myofibroblast marker and CD68 as macrophage infiltration marker. Quantitative evaluation was conducted by electronic image analysis on consecutive low power fields, avoiding glomeruli, and estimated as percentage of the total area or as number of positive cells/field for macrophage infiltration. The renal biopsies were also evaluated for histological characteristics such as percentual area of inflammation infiltration and fibrosis. Clinical and laboratory data were recorded at biopsy moment and followed-up on a period of 17 ± 11 months after the renal biopsy. Interstitial α-SMA immunoexpression proved to be related with interstitial fibrosis (r=-0.47, p<0.001) and macrophage infiltration (r=0.21, p=0.03). Higher immunoexpression of α-SMA was related with renal function assessed by creatinine level at biopsy moment (r=0.32, p=0.002). CONCLUSIONS: In this study, detection of myofibroblast infiltration using α-smooth-muscle actin (α-SMA) proved to be a good marker in describing the initial phases of interstitial fibrosis development in early stages of chronic kidney dysfunction.