No abstract

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 ¼ 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.

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.

Creatinine eGFRcr(ASR) [current] 62 (48-75) 79 (73-86) 74 (68-80) eGFRcr(AS) [new] 60 (46-73) 73 (65-80) 69 (62-75) Cystatin C eGFRcys(AS) [current] 77 (65-87) 87 (81-93) 84 (79-89) Creatinine-cystatin C eGFRcr-cys(ASR) [current] 71 (58-83) 87 (81-93) 82 (76-88) eGFRcr-cys(AS) [new] 65 (52-77) 84 (78-90) 79 (73-85) Percent agreement (95% CI) within 20% of the mGFR, P 20 -% Creatinine eGFRcr(ASR) [current] 40 (27-54) 61 (53-69) 55 (48-62) eGFRcr(AS) [new] 35 (23-48) 53 (45-62) 48 (41-55) Cystatin C eGFRcys(AS) [current] 56 (42-69) 73 (65-80) 68 (61-75) Creatinine-cystatin C eGFRcr-cys(ASR) [current] 52 (38-65) 70 (63-78) 65 (58-72) eGFRcr-cys(AS) [new] 52 (38-65) 68 (61-76) 64 (57-71) Correct classification Percent agreement (95% CI) between the mGFR and eGFR categories -% Creatinine eGFRcr(ASR) [current] 60 (46-73) 70 (62-78) 67 (60-74) eGFRcr(AS) [new] 52 (37-65) 64 (56-73) 61 (54-68) Cystatin C eGFRcys(AS) [current] 65 (52-79) 73 (66-81) 71 (65-78) Creatinine-cystatin C eGFRcr-cys(ASR) [current] 67 (54-79) 74 (66-81) 72 (66-78) eGFRcr-cys(AS) [new] 62 (48-73) 75 (67-81) 71 (64-78) Abbreviations: eGFR, estimated glomerular filtration rate; mGFR, measured glomerular filtration rate. a The performance of each equation in estimating the GFR was evaluated in terms of bias, precision and accuracy, according to the methods described by Inker et al. (2012) 2 and Inker et al. (2021) 4 . b The values indicating the best two equations were italicized and made bold.c Accuracy was calculated as the RMSE relative to the mGFR, the percentage of estimates that differed from the mGFR by less than 30% (P 30 ), and the percentage that differed by less than 20% (P 20 ).