Comparative (1)H NMR metabolomic urinalysis of people diagnosed with Balkan endemic nephropathy, and healthy subjects, in Romania and Bulgaria: a pilot study

Toxins (Basel). 2011 Jul;3(7):815-33. doi: 10.3390/toxins3070815. Epub 2011 Jul 4.


(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.

Keywords: Balkan nephropathy; aristolochic acid; haemodialysis; metabolomics; ochratoxin A; urinalysis.

MeSH terms

  • Aged
  • Balkan Nephropathy / epidemiology*
  • Balkan Nephropathy / urine*
  • Biomarkers / urine
  • Bulgaria / epidemiology
  • Case-Control Studies
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Metabolomics / methods*
  • Middle Aged
  • Multivariate Analysis
  • Pilot Projects
  • Romania / epidemiology
  • Urinalysis / methods*
  • Urinary Tract / physiopathology


  • Biomarkers