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.

Objective Malnutrition is widespread among patients undergoing hemodialysis and is linked to high morbidity and mortality rates. We evaluated the nutritional status and malnutrition markers in patients undergoing hemodialysis in Macao. Methods We performed a cross-sectional analysis of 360 patients in a hemodialysis center. The modified quantitative subjective global assessment (MQSGA), anthropometric indices and related biochemical test data were used to evaluate nutritional status. Results The sample's mean age was 63.47 ± 13.95 years. There were 210 well-nourished (58.3%), 139 mild-to-moderately malnourished (38.6%) and 11 severely malnourished (3.1%) patients. Older patients had a higher incidence of severe malnutrition, but there were no significant differences between diabetic and non-diabetic patients. Mid-arm circumference (MAC); mid-arm muscle circumference; body mass index; triceps skin fold thickness; serum albumin, creatinine and urea; and hemoglobin were all valid for assessing nutritional status. MAC and the serum albumin and creatinine concentrations significantly negatively correlated with MQSGA. Conclusions Malnutrition is commonplace in patients undergoing hemodialysis in Macao, but their nutritional status is not affected by diabetes. Serum creatinine, serum albumin and MAC, and especially pre-dialysis creatinine concentration, represent effective, readily available, and easily remembered screening measures of nutritional status for patients undergoing maintenance dialysis.

Background: With the development of chronic kidney disease (CKD), there are various changes in metabolites. However, the effect of these metabolites on the etiology, progression and prognosis of CKD remains unclear.Objective: We aimed to identify significant metabolic pathways in CKD progression by screening metabolites through metabolic profiling, thus identifying potential targets for CKD treatment.Methods: Clinical data were collected from 145 CKD participants. GFR (mGFR) was measured by the iohexol method and participants were divided into four groups according to their mGFR. Untargeted metabolomics analysis was performed via UPLC-MS/MSUPLC–MSMS/MS assays. Metabolomic data were analyzed by MetaboAnalyst 5.0, one-way ANOVA, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) to identify differential metabolites for further analysis. The open database sources of MBRole2.0, including KEGG and HMDB, were used to identify significant metabolic pathways in CKD progression.Results: Four metabolic pathways were classified as important in CKD progression, among which the most significant was caffeine metabolism. A total of 12 differential metabolites were enriched in caffeine metabolism, four of which decreased with the deterioration of the CKD stage, and two of which increased with the deterioration of the CKD stage. Of the four decreased metabolites, the most important was caffeine.Conclusion: Caffeine metabolism appears to be the most important pathway in the progression of CKD as identified by metabolic profiling. Caffeine is the most important metabolite that decreases with the deterioration of the CKD stage.

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 ).

The effect of trace solvent bisphenol A (BPA) in polyether sulfone hollow fiber membrane Enttex™-16LF (E60) (produced by 3 M) low-throughput dialyzer was tested in this study. Animal experiments were conducted to evaluate its genotoxicity, carcinogenicity, and teratogenicity upon chronic exposure. The dialyzer was operated at 200 mL/min and 400 mL/min and coupled with LC-20AT liquid chromatography to detect BPA, which showed that the BPA content was less than 5 μg/kg/d at both flow rates. In animal experiments, the tolerable intake (T.I.) was calculated to be 0.5 μg/kg/d. With hemodialysis three times per week, the average patient weight was calculated at 70 kg, and the average daily BPA exposure was 0.0306 μg/kg/d. The risk of residual BPA was within the acceptable limit with polyether sulfone membrane Enttex™-16LF (E60) hollow fiber dialyzer from 3 M, without inducing risk for disability, teratogenicity, or genotoxicity.