#5932 BALKAN ENDEMIC NEPHROPATHY AND MALIGNANT TUMOR OF THE UPPER TRACT UROTELIUM: AFTER 45 YEARS
Authors: Glogovac Stevan , Tasic Danijela , Apostolovic Branislav , Dimitrijevic Zorica , Stojanovic Miomir , Petrovic Milan , Sterovic Srdjan , Paunovic Karolina , Prokopovic Miomir , Mitic Branka , Dinic Ljubomir , Mladenovic Slavoljub , Skakic Aleksandar , Bašić Dragoslav 
Published: June 2023

Abstract

Background and Aims
Balkan endemic nephropathy (BEN) is a chronic progressive tubulointerstitial kidney disease of unknown etiopathogenesis described more than 65 years ago. One of the general importance of the disease is the association with malignant tumors of the upper urothelium (MUUT). Epidemiological monitoring of BEN and MUUT plays a particularly important role. In the works published so far, there is a large discrepancy in the results of epidemiological works in relation to the researchers, the period and the region of observation. The aim of this paper was to examine the occurrence of MUUT in endemic settlements for BEN and the ratio of tumor frequency in endemic and non-endemic settlements of the Jablanica district.

Method
The observed research period is from 1978 to 2022. During the study of the frequency of MUUT (malignant tumors of the upper urothelium), the operative material of the urological service of the Leskovac General Hospital was used. The patients were divided according to their place of residence from individual settlements in the Jablanica district, and data from the Nephrology Clinic of the Urgent Clinical Center of Niš were used to classify the settlements: A-endemic settlements of patients with BEN (Balkan endemic nephropathy); B-hypoendemic settlements; C-non-endemic urban and D-non-endemic rural settlements. Some of the analyzes in this work were carried out so that groups A, B are unique endemic and C, D are non-endemic settlements. Data on the total number of inhabitants of the Jablanica district were obtained based on official data from the population census in 1981, 1991, 2002, 2011 and 2022. The incidence rate was calculated per 100,000 inhabitants. For practical reasons, the observed period is divided into the first (1978-2002) and the second (2003-2022).

Results
In the period from 1978 to 2022, 106 MUUT (55 men and 51 women) were registered in the Jablanica district, and the PGSI was 0.924. In endemic settlements (A) there were 14, hypoendemic (B) 10, non-endemic urban (C) 25 and in non-endemic rural (D) 57 MUUT. In the first observation period, the PGSI in Jablanica district was 1.3, and in the second, 0.53. In endemic settlements (A) in the first period, the frequency of MUUT was 9.1 times higher than in the second (17.56/1.93), while in hypoendemic ones (B) the frequency was 3.2 times higher in the first compared to the second observation period (5.06/1.58). In the last five years of observation (2018-2022), not a single MUUT was registered in the Jablanica district, and in the endemic settlements (A.B) only three tumors were registered in the last 25 years. In the observed period, the linear trend in endemic settlements (A) was in a statistically significant decline (y = - 0.0276+55.691; r2 = 0.2128), while in the first period (1978-2002) it was in a statistically weak decline (y = - 0.0054+ 0.59; r2 = 0.0031) and in the second period (2003-2022) it is not valid because only one tumor was registered. In the observed period, the linear trend of BEN incidence was in a statistically significant decrease (y = - 0.164x +6.0669; r2 = 0.788).

Conclusion
The high frequency of MUUT in endemic settlements for BEN in the first period of observation, perhaps indicates a common nephropathogenic and carcinogenic etiological factor, and therefore the more correct name of the disease may be Balkan nephrouropathy. In the observed period, we have a large discrepancy in results compared to the observation periods, and one of the main reasons is the drastic decrease of patients with BEN in endemic settlements, and the reasons should be sought in the lower toxicity of the causative agent, better water supply, better health awareness of patients, health and construction prevention and not having marriage between at-risk patients. Is BEN disappearing?