Contemporary Approach to Balkan Endemic Nephropathy
DOI:
https://doi.org/10.5644/Radovi.364Keywords:
Balkan endemic nephropathy, epidemiology, pathogenesis, etiology, ochratoxin A, arislolochic acid, polycyclic aromatic hydrocarbons, molecular biologyAbstract
Balkan endemic nephropathy (BEN) is a progressive disease with insidious course inevitably leading to terminal uremia. Histology reveals focal tubular atrophy, focal non-destructive, hypocellular interstitial sclerosis, focal segmental and global glomerulosclerosis of collapsed type and intimal hyalinosis of arterioli and interlobular arteries. Association of upper urothelial tumors (LJUT) with BEN is striking. It seems that the most likely underlying pathological mechanism is the slow intoxication in genetically predisposed subjects. Hypothetical agents act upon tubular epithelial and endothelial cells. It exerts pathological effects via interfering with metabolism and through direct genotoxicity thereby disturbing cell cycle and initiating apoptosis that appears to be the underlying mechanism of atrophic changes. Target cells express the genes that are normally inactive and subsequently produce cytokines and complement thereby transforming into proinflammatory cells. Affected cells seem to undergo trans differentiation, i.e. expression of mesenchymal markers with subsequent production of collagen as extracellular matrix that triggers sclerosis. The mechanism of malignant alteration seems to be the same and agent to induce it also seems to be the BEN-inducing agent. Regarding etiology, epidemiological studies have revealed elevated concentrations of many putative nephrotoxins in BEN area, but their particular concentrations still do not reach the toxic ones. Nevertheless, it seems reasonable to keep insisting on pathogenesis of known models of toxic nephropathies, especially in the light of recent advances in molecular biology. Ochratoxin A (OTA), aristolochic acid (AA) and polycyclic aromatic hydrocarbons (PAH) represent such models. Further research will help us understand them better, understand their toxic metabolites that are supposed to contribute to development of the disease as well as to better understand other concomitant and synergistic factors from endemic areas that might participate in that development.
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