Endemic nephropathy is a chronic tubulointerstitial disease with a latent onset and slow progression to end-stage renal disease. It affects both men and women living in certain endemic rural areas located around the tributaries of the Danube in Romania, Bulgaria, Croatia, Bosnia and Herzegovina, Kosovo and Serbia. It is estimated that almost one hundred thousand people are at risk of developing the disease, while there are currently more than twenty-five thousand patients, and the prevalence is about 2-5 %. The natural course of the disease is characterized by a long incubation period, nonspecific and difficult to recognize clinical signs and symptoms, and a high incidence of the development of a malignant tumor of the transitional epithelium of the upper part of the urinary tract with a frequency of up to 50 %. The highlighted feature includes a family pattern in conjointed households in which several members of the same household who are not necessarily related by blood can develop the disease. Over the years, a large number of potential etiological factors have been proposed, most of which have been disproved. The main environmental cause of nephropathy and urothelial carcinoma is chronic poisoning with aristolochic acid, which is found in the seeds of the birthwort plant (Aristolochia clematitis L.). Specific biomarkers used to assess exposure to carcinogenic and nephrotoxic aristocholic acid are aristolactam DNA adducts detected in kidney tissue and urinary tract cancers. They also induce specific mutations in the p53 tumor suppressor gene that will further affect the stages of carcinogenesis. The genetic predisposition of vulnerable individuals has a secondary role as an endogenous etiological factor. Today, there are simple measures to control and reduce the growth of birthwort with the aim of preventing or eliminating aristolochic acid contamination.