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(1)H NMR spectroscopy of urine has been applied to exploring metabolomic differences between people diagnosed with Balkan endemic nephropathy (BEN), and treated by haemodialysis, and those without overt renal disease in Romania and Bulgaria. Convenience sampling was made from patients receiving haemodialysis in hospital and healthy controls in their village. Principal component analysis clustered healthy controls from both countries together. Bulgarian BEN patients clustered separately from controls, though in the same space. However, Romanian BEN patients not only also clustered away from controls but also clustered separately from the BEN patients in Bulgaria. Notably, the urinary metabolomic data of two people sampled as Romanian controls clustered within the Romanian BEN group. One of these had been suspected of incipient symptoms of BEN at the time of selection as a 'healthy' control. This implies, at first sight, that metabolomic analysis can be predictive of impending morbidity before conventional criteria can diagnose BEN. Separate clustering of BEN patients from Romania and Bulgaria could indicate difference in aetiology of this particular silent renal atrophy in different geographic foci across the Balkans.

Balkan Endemic nephropathy (BEN) is a tubulointerstitial disease of unknown etiology signaled in a limited geographical area. In the neighbourhood of endemic villages are coal deposits from the Pliocene, that contain toxic substances that by mobilizing groundwater can leach in water sources used by the inhabitants. In the present paper the possible impact of the coal from Pliocene on people that worked many years in mines in the endemic County Mehedinti, Romania, and who lived in this area are analysed. The risk of toxicity of coal was theoretically increased in miners because they consumed frequently water from mine springs that came from coal layers, while at home water from wells could have been contaminated by toxic substances from coal. It has been found that only 5 of the 96 patients with BEN were under dialysis program in 2008. Also out of 34 former miners only 3 had GFR < 60 ml/min/1.73 sqm, and only one with creatinine of 3 mg/dl had GFR < 30 ml/min/1.73 sqm. The mean GFR in the 34 miners was: 94.13 +/- 26.58 ml/min/1.73 sqm. We analysed GFR and proteinuria in persons from the endemic zone from 2 types of villages: some with mining activity presently (Husnicioara) others where presently there are no mining activities (Hinova, Bistrita, Livezile). We also analysed comparatively 2 non-endemic localities near the endemic focus: Drobeta Turnu Severin (without mining activity) and Motru with mining activity where different coal deposits are (non-Pliocene). Data were provided from the family doctors databases. The GFR was lower in the inhabitants from the endemic villages Bistrita and Hinova than in the investigated inhabitants from the non-endemic town Drobeta Turnu Severin (p = 0.008 and p = 0.0004 respectively). Inhabitants from the endemic village Husnicioara (Pliocene coal mine still functioning) had a higher GFR than inhabitants from Drobeta Turnu Severin and higher than inhabitants from the endemic village Livezile (mine closed 10 years ago): p = 0.0055 and p = 0.001 respectively, but a lower than the investigated inhabitants from the non-endemic town Motru (where a non-Pliocene coal mine is functioning): p < 0.001. Proteinuria was present in 8.03% of the inhabitants from the endemic village Bistrita and in 7.4% of the inhabitants from the endemic village Hinova. In the non-endemic town Drobeta Turnu Severin, proteinuria was present in 7.08% of the investigated inhabitants. Proteinuria was present in 0.78% of the investigated inhabitants of the non-endemic town Motru (where a non-Pliocene coal mine is functioning) and 2.5% of the inhabitants of the endemic village Husnicioara (Pliocene coal mine still functioning). Our paper does not show any relationship between exposure to Pliocene coal and the etiology of BEN.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephritis seen primarily in countries in the Balkan Peninsula. The disease, which was first described in Romania 50 years ago, often manifests as a form of chronic nephritis that is also associated with upper urothelial cancers (UUC). This review summarizes the observations and studies performed in Romania regarding this disease during the last 50 years with particular emphasis on Mehedinti county. The paper analyzes current data on the epidemiology of the disease in this area, specifically in relation to the observations made in dialysis centers in the same area. It also discusses the diagnostic criteria of patients with BEN stemming from collaborations between specialists working in other countries affected by the disease. Moreover, the paper analyzes the main etiological factors suspected to play a role in BEN: aristolochic acid (the disease has many similarities to aristolochic nephropathy caused by Chinese herbs), mycotoxins, toxic substances from pliocene lignite, genetic factors, and viruses. Studies performed by Romanian authors are presented briefly in comparison to studies performed by other authors. Finally, given that BEN is an important health problem in the region, the relationship between BEN and UUC is further analyzed.

Balkan endemic nephropathy (BEN) is a disease found in Romania and neighboring countries in the Balkan area. In Romania, BEN is most prevalent in Mehedinti County, located in the South of Romania near the Danube River. The etiology of the disease is as yet unknown. One of the current hypotheses concerning BEN etiology is an involvement of aristolochic acid (AA). BEN bears many similarities to aristolochic nephropathy, which is developed due to the use of Chinese herbs as therapeutic remedies in slimming diets. This paper analyzes the involvement of therapeutic remedies based on AA in the BEN found in Mehedinti County, where these herbs have been traditionally used. The presence of AA in the plasma of BEN patients as well as of other subjects, including healthy relatives of these patients and other persons from the BEN-affected area, has been analyzed. No AA was detected in the plasma of the studied subjects. This proves the absence, at the current time, of an AA contribution in the analyzed subjects. Therapeutic remedies based on AA have been used in the BEN-affected area. We were not able to reveal direct relationships between these remedies and either the development of BEN in dialyzed patients or the development of urinary-tract tumors in dialyzed patients with urothelial tumors. Therapeutic remedies based on Aristolochiaclematitis may play a stimulating role in BEN with regard to its development and the development of urinary-tract tumors. There may be a relationship between BEN and cumulative previous exposure to low doses of AA due to the consumption of contaminated foodstuffs, which could add to any contributions by therapeutic remedies.