Vol. 9, No 1, 2002 pp. 82 - 87
UC 616.61-004 616.611 616.612 
PATHOLOGY OF BALKAN ENDEMIC NEPHROPATHY –
A CORRELATION WITH ESTABLISHED KIDNEY DISEASE ENTITIES
Dušan Ferluga1, Asta Hvala1, Senaid Trnačević2, Ahmet Halilbašić2, Mato Vukelić3, Josip Čeović4, Alenka Vizjak1
1Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
2Department of Nephrology and Dialysis, University Medical Center, University of Tuzla, Tuzla, Bosnia and Herzegovina
3Department of Pathology, Dr Josip Benčević General Hospital, Slavonski Brod, Croatia
4Dr Josip Benčević General Hospital, Slavonski Brod, Croatia
Summary. The aim of the paper was to summarize the results of autopsy studies of end-stage Balkan endemic nephropathy (BEN), to compare the results of our biopsy studies of earlier stages with those of other research groups and to discuss the issue of the most up-to-date hypothesis about the pathogenesis of this still enigmatic disease. Our experiences have been based on light microscopic examination of 12 end-stage autopsy cases, 4 nephrectomies from patients from endemic areas with urothelial upper urinary tract tumors and a systematic study by light, immunofluorescence and electron microscopy techniques of strictly selected kidney biopsies from 50 patients with earlier stages of BEN. End-stage pathology is characterized by extremely small sized, smoothly surfaced contracted kidneys, showing a peculiar cortical histotopography of sclerosing atrophy and frequent association with urothelial upper urinary tract tumors. Characteristically pronounced condensation of sclerosing atrophy of all nephron compartments, particularly tubulo-interstitial, in the outer subcapsular cortex is similar to that of Chinese herbs nephropathy and vascular nephrosclerosis. Multifocal chronic inactive sclerosing non-specific lesions regularly found in the kidneys of earlier stages of BEN may suggest accelerated ageing triggered by long-lasting low-dose exposure to an unknown environmental nephrotoxic and mutagenic agent similar to ochratoxin A and aristolochic acid. Significantly less extensive but not infrequent additional biopsy findings, sharing similarities with the histopathology of chronic cyclosporine nephrotoxicity, indicate endothelial cells of small intrarenal blood vessels to be an important target in the pathogenesis of BEN.
Key words: Balkan endemic nephropathy, pathology, electron microscopy, etiopathogenesis