The significance of apoptosis for early diagnosis of Balkan nephropathy

Balkan nephropathy—a toxic nephropathyBalkan nephropathy is a non-destructive, low inflam-matory, progressive tubulointerstitial disease. It fre-quently and exclusively occurs in inhabitants ofsome rural areas along tributaries of large rivers inex Yugoslavia, Bulgaria and Romania. Focal changesof kidney parenchyma are characterized by atrophyand segmental disappearance of tubuli with consid-erable (acellular) interstitial fibrosis contrasting withrelatively preserved glomeruli. The renal insufficiencyaggravates gradually, 5–30% of these patients fromdifferent districts had to undergo regular haemo-dialysis w1x. Severe anaemia with insufficient synthesisof erythropoietin is more pronounced as that seen inother kidney diseases w2x. The other disease affectingthe population of endemic regions is (upper) urothelialcancer, occurring with a 100 times greater incidencethan in the general population w3x. In spite of scientificefforts, the aetiology of Balkan nephropathy andassociated urothelial carcinomas have not been fullyunderstood.Two almost regular microscopical findings in kidneytissue obtained by biopsy in the initial phase of Balkannephropathy may help to elucidate the nature of theselesions. These are discrete foci of tubular atrophyanduor mild vascular lesions of intertubular capillariesand afferent arterioles w4x. These lesions apparently leadto capillarosclerosis and arteriolar hyalinosis in dis-tinct areas of the parenchyma with tubular atrophy,starting from the superficial part of the cortex. Basedon the observation that the kidneys in Balkan neph-ropathy show similarities with other numerous toxicnephropathies (due to analgesic abuse, mycotoxinsochratoxin A, aristolochic acid, cyclosporine A), atoxic aetiology of Balkan nephropathy is plausible,numerous factors are likely to act synergistically in thetubuli. Toxic agents or their metabolites directly affectthe vasculature and tubuli w1x while resulting ischaemiamay assist in the development of focal tubular lesionsw2x. Mycotoxin ochratoxin A highly contaminates foodin several investigated endemic villages w5x. OchratoxinA is a nephrotoxin with carcinogenic potential w6x.