Vol.6, No 1, 1999 pp. 53 - 58
UC 616.61 
BALKAN ENDEMIC NEPHROPATHY. A REAPRRISAL AFTER FORTY YEARS
Vladisav Stefanović
Institute of Nephrology and Hemodialysis, Faculty of Medicine, Niš,Yugoslavia
e-mail: stefanovic@cent.co.yu
Summary. Balkan endemic nephropathy (BEN) was described in 1957, and this review gives an account of research forty years later. The etiology remains the main unanswered problem in BEN despite broad investigations conducted into the possible role of genetic factors, environmental agents and immune mechanisms.The evidence accumulated so far indicates that BEN is an environmentally-induced disease. A continuous, but cyclic, effect of environmental factors upon kidneys of children from the endemic settlements and endemic families in particular was demonstrated. Weathering of low-rank coals nearby the endemic villages produces water soluble polycyclic aromatic hydrocarbons and aromatic amines, similar to metabolic products of acetaminophen that has a causal relationship with analgesic nephropathy. Many of these compounds are known to be carcinogenic and could also cause urothelial cancer. The similarity of the morphological and clinical pattern of BEN and Chinese herb nephropathy has raised the possibility of a common etiologic agent, aristolochic acid. Genetic studies have landed support for genetic predisposition to BEN.
Kidney morphology in early stages of the disease is peculiar and resembles that of aging with pronounced renal vascular changes. The histopathology is predominantly tubulointerstitial sclerosis without infiltrates. Humoral immune mechanisms do not appear to play a pathogenic role in BEN.
An increased incidence of tumors of renal pelvis and ureter in patients with BEN and in population from endemic settlements has been observed. Recently the frequency of urinary bladder tumors in endemic settlements was also found increased compared with the nonendemic villages and cities. The geographic correlation between BEN and urinary tract tumors supports the speculation that these diseases share a common etiology.
Key words: Balkan endemic nephropathy, urothelial cancer, etiology, prevention
BALKANSKA ENDEMSKA NEFROPATIJA. RAZMATARNJE POSLE ČETRDESET GODINA

Kratak sadržaj. Balkanska endemska nefropatija (BEN) opisana je 1957. godine, a ovaj pregled daje dostignuća četrdesetogodišnjih istraživanja. Etiologija je najvažniji nerešeni problem u BEN, uprkos brojnim ispitivanjima moguće uloge genetskih faktora, faktora sredine i imunih mehanizama. Izneto je dovoljno dokaza da je BEN izazvana faktorima sredine. Pokazano je neprekidno, ciklično delovanje faktora sredine u endemskim naseljima na bubreg dece, posebno one iz endemskih porodica. Ispiranje mladih ugljena (lignita) u okolini endemskih naselja proizvodi u vodi rastvorljive aromatične ugljovodonike i aromatične amine, slične metaboličkim produktima acetaminofena, koji imaju ulogu u nastanku analgezične nefropatije. Mnogi od ovih produkata su kancerogeni i mogu dovesti do raka urotelijuma. Sličnost morfologije i kliničke slike BEN i Nefropatije izazvane kineskim travama, istakla je moguću etiološku ulogu aristolohične kiseline. Genetske studije su dale osnova za genetsku predispoziciju za BEN.
Morfologija bubrega u ranoj fazi BEN je posebna i vrlo slična starenju, sa izraženim renalnim vaskularnim promenama. Histopatološki predominira tubulointersticijska skleroza bez ili sa retkim infiltratima. Izgleda da humoralni imuni mehanizmi ne igraju ulogu u BEN.
U bolesnika sa BEN i stanovnika endemskih naselja nadjena je povećana učestalost tumora pijeluma i uretera. Skoro je opisana i povećana učestalost tumora bešike. Geografska korelacija izmedju BEN i tumora urinarnog trakta sugeriše da ove bolesti mogu da imaju zajedničku etiologiju.
Ključne reči: Balkanska endemska nefropatija, rak urotelijuma, etiologija, prevencija