Background: Metabolomics is useful in elucidating the progression of diabetes; however, the follow-up changes in metabolomics among health, diabetes mellitus, and diabetic kidney disease (DKD) have not been reported. This study was aimed to reveal metabolomic signatures in diabetes development and progression. Methods: In this cross-sectional study, we compared healthy (n = 30), type 2 diabetes mellitus (T2DM) (n = 30), and DKD (n = 30) subjects with the goal of identifying gradual altering metabolites. Then, a prospective study was performed in T2DM patients to evaluate these altered metabolites in the onset of DKD. Logistic regression was conducted to predict rapid eGFR decline in T2DM subjects using altered metabolites. The prospective association of metabolites with the risk of developing DKD was examined using logistic regression and restricted cubic spline regression models. Results: In this cross-sectional study, impaired amino acid metabolism was the main metabolic signature in the onset and development of diabetes, which was characterized by increased N-acetylaspartic acid, L-valine, isoleucine, asparagine, betaine, and L-methionine levels in both the T2DM and DKD groups. These candidate metabolites could distinguish the DKD group from the T2DM group. In the follow-up study, higher baseline levels of L-valine and isoleucine were significantly associated with an increased risk of rapid eGFR decline in T2DM patients. Of these, L-valine and isoleucine were independent risk factors for the development of DKD. Notably, nonlinear associations were also observed for higher baseline levels of L-valine and isoleucine, with an increased risk of DKD among patients with T2DM. Conclusion: Amino acid metabolism was disturbed in diabetes, and N-acetylaspartic acid, L-valine, isoleucine, asparagine, betaine, and L-methionine could be biomarkers for the onset and progression of diabetes. Furthermore, high levels of L-valine and isoleucine may be risk factors for DKD development.

Mitochondrial DNA (mtDNA) released into extracellular subsequent to cell injury and death can promote inflammation in patients and animal models. However, the effects of peritoneal dialysate cell-free mtDNA on intraperitoneal inflammation and peritoneal solute transport rate (PSTR) in peritoneal dialysis (PD) patients remain unclear. We select the incident patients who began PD therapy between January 1, 2009, and December 30, 2010. Peritoneal dialysate was collected at the time of peritoneal equilibration test. The cell-free mtDNA, IL-6, IL-17A, TNF-α and IFN-γ were measured. All patients were followed till December 2017. The results were compared with PSTR and patient survival. One hundred and eighty-nine patients were included in the study. The average age was 47.1 ± 13.5 years, 55.6% of the patients were males. The average PSTR was 0.66 ± 0.12, the median dialysate mtDNA levels were 4325 copies/ul. The median concentrations of IL-6, IL-17A, TNF-α and IFN-γ were 25.9, 10.8, 25.8 and 17.9 pg/ml, respectively. We found that dialysate mtDNA was significantly correlated with PSTR (r = 0.461, P < 0.001), IL-6 (r = 0.568, P < 0.001), TNF-α (r = 0.454, P < 0.001) and IFN-γ (r = 0.203, P = 0.005). After adjustment for multiple covariates, dialysate mtDNA levels were independently correlated with IL-6 and PSTR. Dialysate mtDNA levels were not associated with patient survival. We found that dialysate mtDNA levels correlated with the degree of intraperitoneal inflammatory status in PD patients. Peritoneal effluent mtDNA was an independent determinant of PSTR but did not affect patient survival.

The association between adherence to the planetary health diet and chronic kidney disease (CKD) remains under characterized. This study aim to investigate the association of planetary health diet index (PHDI) with the risk of CKD and assess potential effect modification by genetic predisposition. A large, population-based cohort study was conducted using data from UK Biobank. Eligible participants included those without a history of CKD who completed at least one 24 -h dietary recall questionnaire. Three distinct planetary health diet indexes (PHDIs) were used to assess dietary adherence. A polygenic risk score (PRS) for CKD was calculated to evaluate genetic susceptibility. Cox proportional hazards models were used to estimate the associations between the PHDI and the risk of incident CKD. The joint effects of PHDI and genetic susceptibility were further examined. Sensitivity analyses were conducted to evaluate the robustness of the findings. A total of 139,165 participants were included in the primary analysis. Over a median follow-up of 13.3 years, 6,391 incident CKD cases were identified. Compared with participants in the lowest adherence category, the hazard ratios (HRs) of incident CKD for those in highest adherence were 0.827 (95% CI, 0.757-0.904), 0.865 (95% CI, 0.805-0.929), and 0.891 (95% CI, 0.821-0.996) for Stubbendorff PHDI, Colizzi PHDI and Knuppel PHDI, respectively. Participants with highest adherence to planetary health diet and low genetic risk showed the lowest risk of CKD, with HRs of 0.707 (95% CI, 0.600-0.832), 0.682 (95% CI, 0.597-0.778), and 0.770 (95% CI, 0.663-0.893) across the three different PHDIs. These associations remained robust in several sensitivity analyses. Higher adherence to the planetary health diet was associated with lower risk of CKD, and these effects were enhanced by jointing with genetic susceptibility. Promoting this sustainable dietary pattern may play a key strategy for CKD prevention.

Objective: To investigate the association between night shift work and chronic kidney disease (CKD) risk and evaluate the interacting role of genetic susceptibility. Methods: This prospective cohort study included 252,425 participants from the UK Biobank for current night shift analysis and 67,097 for lifetime exposure. Cox proportional hazards models assessed the relationship between various shift patterns and CKD incidence. Formal interaction analyses (additive and multiplicative scales) and sensitivity analyses were conducted. Reporting followed STROBE guidelines. Results: Compared to those who never or rarely worked night shifts, permanent night shift workers had a significantly higher CKD risk (HR 1.19, 95% CI 1.06–1.34). Lifetime analyses revealed significant associations between incident CKD risk and duration, frequency, shift length, and consecutive shifts. Participants with high genetic risk and permanent night shift exposure had the highest CKD risk (HR 2.49, 95% CI 2.07–2.99). Potential interactions between genetic susceptibility and specific night shift patterns were suggested ( P < 0.05). Sensitivity analyses further confirmed the robustness of these associations. Conclusions: Night shift work—particularly permanent schedules and adverse shift patterns—increases the risk of CKD, especially among individuals with high genetic predisposition. Optimizing shift schedules may help reduce CKD incidence.

Chronic kidney disease (CKD) is a major public health issue, and smoking is a key modifiable risk factor. This study aimed to assess the associations of smoking and smoking cessation with incident CKD in later life, as well as the joint effects and interactions with genetic susceptibility. Prospective cohort study. A total of 427,396 UK Biobank participants with available smoking and kidney function data, free of CKD at baseline (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m² and the urine albumin-creatinine ratio ≤30 mg/g), were included in this study. Smoking status, including current smoking, former smoking, and smoking cessation during follow-up, was assessed using repeated touchscreen questionnaires. Incident CKD identified using International Classification of Diseases, 10th Revision, and Office of Population Censuses and Surveys Classification of Interventions and Procedures4 codes from primary care, hospital inpatient, and death registry records, with baseline CKD defined as estimated glomerular filtration rate < 60 mL/min/1.73 m² or albuminuria >30 mg/L. Cox proportional hazards regression models were used to estimate the association between smoking status and incident CKD, with secondary and sensitivity analyses performed to confirm the robustness of the findings. Among 191,774 smokers included in the primary analysis, 13,726 incident cases of CKD were documented over a median follow-up of 13.5 years. Compared with current smokers, quitters had the lowest risk of CKD (HR, 0.69; 95% CI, 0.57-0.84), and former smokers also showed a significantly reduced risk (HR, 0.80; 95% CI, 0.76-0.83) after full adjustment. Potential misclassification of smoking and cessation status, possible under-ascertainment of CKD, residual confounding, and limited generalizability. Smoking cessation was associated with a reduced risk of CKD compared with continued smoking.