Exploration of Apoptosis in Histopathologies of Balkan Endemic Nephropathies with Both Urothelial Tumour and Atrophied Kidney

Abstract

There seems yet no satisfactory explanation for the mysterious endemic renal disease, known as Balkan endemic nephropathy (BEN), seen across rural parts of several Balkan countries in the last century although some have claimed aristolochic acid as the etiologic agent. Nearly half of the BEN patients develop urothelial cancers and unilateral nephrectomy may be temporary life-extending measure for some cases. Recent access to some tissues of archived Serbian unilateral nephrectomy specimens during the past century enabled description of unique tumour immuno-profiles. We also evaluated the role of apoptosis using a modern TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. We found clear evidence of apoptosis in regions of several tumour specimens and adjacent healthy kidney tissues. These observations suggest a prominent role of apoptosis in the pathogenesis of BEN and the associated urothelial cancers and point to the need for systematic evaluation of apoptosis in other archived tissues from BEN patients. Here, we also present evidence of apoptosis in kidney sections of male rats treated with ochratoxin A. These observations suggest a prominent role of apoptosis in the pathogenesis of BEN and the associated urothelial cancers and point to the need for systematic evaluation of apoptosis in other archived tissues from BEN patients. Here, we also present evidence of apoptosis in kidney sections of male rats treated with ochratoxin A. Fungal metabolites such as ochratoxin A and alkaloids from the Aristolochia plants are nephrotoxic in both animals and humans, and experimental animal models could be helpful in understanding the pathophysiology of kidney disease and tumorigenesis in humans exposed to such agents.