Identification of Metabolite Markers Associated with Kidney Function.

Background: Chronic kidney disease (CKD) is a global public health problem. Identifying new biomarkers that can be used to calculate the glomerular filtration rate (GFR) would greatly improve the diagnosis and understanding of CKD at the molecular level. A metabolomics study of blood samples derived from patients with widely divergent glomerular filtration rates could potentially discover small molecule metabolites associated with varying kidney function. Methods: Using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), serum was analyzed from 53 participants with a spectrum of measured GFR (by iohexol plasma clearance) ranging from normal to severe renal insufficiency. An untargeted metabolomics assay (N » 214) was conducted at the Calibra-Metabolon Joint Laboratory. Results: From a large number of metabolomics-derived metabolites, the top 30 metabolites correlated to increasing renal insufficiency according to mGFR were selected by the random forest method. Significant differences in metabolite profiles with increasing stages of CKD were observed. Combining candidate lists from six other unique statistical analyses, six novel, potential metabolites that were reproducibly strongly associated with mGFR were selected, including erythronate, gulonate, C-glycosyltryptophan, N-acetylserine, N6-carbamoylthreonyladenosine, and pseudouridine. In addition, hydroxyasparagine were strongly associated with mGFR and CKD, which were unique to this study. Conclusions: Global metabolite profiling of serum yielded potentially valuable biomarkers of different stages of CKD. Additionally, these potential biomarkers might provide insight into the underlying pathophysiologic processes that contribute to the progression of CKD as well as improve GFR estimation.

An in vitro study of the antioxidant activities and effect on human DNA of the Chinese herbal decoction 'Liu Wei Di Huang'.

A Chinese medicinal formulation, 'Liu Wei Di Huang', and its individual components have been tested for the genoprotective effect on human DNA by the comet assay. Results showed no DNA protection contributed by this prescription. However, the aqueous extracts of individual herbs, namely Cortex Moutan and Rhizoma Dioscoreae, were able to decrease by 10-15% the DNA stand break from hydrogen peroxide-mediated oxidative stress. This provides insight to further evaluate the interaction among herbs and the search for the active ingredient responsible for the DNA protective effect.