Trends in Incidence and Prevalence of Balkan Endemic Nephropathy in the Three Most Affected Villages in Serbia Over a 36-Year Period

Abstract

The study was undertaken with the aim to evaluate trends in incidence and prevalence of Balkan endemic nephropathy (BEN) in the villages Šopić, Petka, and Vreoci, Lazarevac municipality, Serbia. Data concerning BEN notifications in the population-based registry of the Special Hospital for Endemic Nephropathy, Lazarevac were used to evaluate BEN incidence rates in the three villages over the period 1973À2008. Population estimates were based on national census data. All age-adjusted incidence rates were standardized to the European standard population and trends were assessed by Poisson regression model and joinpoint analysis. The prevalence of BEN was obtained in cross-sectional studies carried out in the villages Šopić (1971 and 1992), Vreoci (1971and 2002), and Petka (1971 and 2008. The overall agestandardized incidence rates of BEN in the three villages changed over time. The significant 8.6% annual decrease in the first 16 years of the observed period was followed by a slight increase of 4.6% annually in the last two decades. The agestandardized incidence rates changed over time, being the greatest in the years when the field investigations were made. There was an insignificant change in BEN prevalence in Šopić and Vreoci and a significant decrease in prevalence in Petka. During a 36-year period, 367 new cases of BEN were registered in the three endemic villages and the overall agestandardized incidence rate varied over time. As BEN is a slow-progressing and asymptomatic chronic kidney disease, early detection of BEN can only be achieved by field examination.

Balkan Endemic Nephropathy and the Causative Role of Aristolochic Acid

“…21 Similar trends were observed in Serbia. 22,23 An early hallmark of BEN is proximal tubule damage, which is manifested as low-molecular-weight (tubular) proteinuria and enzymuria that are in line with the pathologic findings: good preservation of glomeruli and a gradient of tubular atrophy with severe interstitial fibrosis that decreases in severity from outer-to-inner cortex. Two target tissues were identified in BEN patients: proximal renal tubular cells, leading to interstitial fibrosis and eventually chronic renal failure, and urothelial (transitional) cells, leading to a high prevalence of UTUC.…”

Geographic distribution and risk of upper urothelial carcinomas in Croatia, 2001–2011

“…Conflicting BEN estimates amongst the endemic foci continue to exist [16–23]. This is, in part, due to the adaptation of different sets of diagnostic criteria over the years.…”

“…In Croatia, 14 villages in the southwestern part of Brod-Posavina County, located in the flood plains of the Sava River, are considered endemic for BEN [9, 14]. Recent findings from several studies suggest a decline in BEN incidence [15–19]; however, conflicting results still exist [20–23]. As for UUC incidence, it appears to be declining according to Markovic et al, who reported a decrease in UUCs over a 30-year period when endemic areas for BEN were compared to non-endemic areas in Serbia (57.1-fold in 1969–1988 vs. 11.2-fold in 1989–1998) [15].…”

Endemic nephropathy: A disease that requires further research

“…Posle veoma obimnih studija skrininga početkom sedamdesetih godina prošlog veka, skrining u endemskim selima nije rađen preko dve decenije, a ponovljen je u periodu između 1990. i 2002. godine samo u tri sela u opštini Lazarevac. Tada su otkriveni mnogi novi bolesnici, što je uticalo na stopu incidencije u godinama skrininga (15,16,19). To ukazuje da bez obimnih i redovnih studija skrininga u endemskim naseljima ne mogu pravilno da se procene incidencija i prevalencija EN.…”