Damage to Kidney in Balkan Endemic Nephropathy: Initial Lesion, Target Structures and Pathomorphogenesis

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease of unknown etiology. Not only the etiology of the disease but even the initial lesion, target nephron structure and morphogenesis remain unresolved. We have previously performed quantitative morphometric analysis on kidney biopsy specimens of patients in different stages of BEN (without renal failure, with initial and advanced renal failure). In the initial stage of the disease, when glomerular filtration rate is normal, the increase of cortical interstitium and a reduction of glomerular volume are demonstrated. A significant reduction of the tubular epithelium volume density is characteristic of the advanced stage. The number of renal interstitial capillaries per 0.1 mm, and the lenght density expressed per mm, both significantly decreased in BEN patients with normal kidney function (p<0.01) and with renal failure (p<0.001). We have also investigated the immunolocalization of laminin, cytokeratin and vimentin in the kidney of patients in different stages of BEN. In the early stages of BEN a marked overexpression of laminin in renal interstitial capillaries was observed with a moderately increased expression in tubules. Later stages were characterized by intensive expression of laminin in atrophic tubules, much more in proximal than in distal ones. The coexpression of vimentin and cytokeratin in proximal tubular cells was also demonstrated. Evidence is presented that renal vascular changes occur early in BEN. A significant role of tubular injury in the pathogenesis of BEN was supported by the finding of vimentin and cytokeratin coexpression in the tubular epithelial cells. Interstitial sclerosis could result from the overproduction of extracellular matrix by injured proximal tubular epithelium and interstitial capillary endothelial cells. The changes described, particularly those taking place at the level of interstitium, bear the key responsability for the BEN progression.