Search

Objectives: Cross-sectional evidence has shown that frailty is highly prevalent in patients with chronic kidney disease (CKD). However, there is limited evidence of the longitudinal associations between frailty, genetic predisposition to CKD, and the risk of CKD in the general population. Therefore, this study aimed to examine such associations among participants in the UK Biobank., Study Design: This is a prospective cohort study included 370,965 middle-aged and older adults from the UK Biobank. Physical frailty was assessed using a modified version of the Fried phenotype classification. A weighted genetic risk score was built using 263 variants associated with estimated glomerular filtration rate., Main Outcome Measures: Incident CKD was identified from hospital inpatient records., Results: Over a median follow-up of 12.3 years, we documented a total of 11,121 incident CKD cases. Time-dependent Cox proportional hazards regression models indicated that individuals with frailty (hazard ratio [HR]: 1.94, 95 % confidence interval [CI]: 1.81-2.08) and pre-frailty (HR: 1.27, 95 % CI: 1.22-1.33) had an increased risk of developing CKD, compared with non-frail individuals. No significant interaction between frailty and genetic risk score was observed (P for interaction = 0.41). The highest risk was observed among the individuals with high genetic risk and frailty (HR: 2.31, 95 % CI: 2.00-2.68)., Conclusion: Our results demonstrated that frailty and pre-frailty were associated with increased risk of incident CKD in middle-age and older adults, regardless of genetic risk of CKD. Our study underscores the importance of frailty screening and intervention as a potential strategy to prevent CKD. Future clinical trials are needed to validate our findings., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background : Emerging studies suggest that focusing on the intake of specific types or sources of sugars may yield greater benefits in preventing chronic kidney disease (CKD). Objective : We aimed to investigate the associations between free and non-free sugar intakes and CKD risk as well as the potential sugar type-gut microbiome interactions. Methods : A total of 138 064 participants from the UK Biobank were included in this prospective study. The free and non-free sugar intakes were assessed using repeated web-based 24-hour dietary recalls. A cause-specific competing risk model was used to estimate hazard ratios (HRs) and the corresponding confidence intervals (CIs) of incident CKD, treating deaths before incident CKD as competing events. Results : During a median follow-up of 10.5 years, 2,923 participants (2.1%) developed CKD. The free sugar intake was positively associated with the risk of CKD (HR quartile 4 vs. quartile 1 = 1.32, 95% CI = 1.18, 1.47), with a nonlinear relationship ( P for nonlinearity = 0.01, the risk increased rapidly after free sugars made up 10% of the total energy). The non-free sugar intake was inversely associated with CKD risk (HR quartile 4 vs. quartile 1 = 0.68, 95% CI = 0.60, 0.77), with an L-shaped nonlinear curve ( p for nonlinearity = 0.01, the turning point was at 13.5% of the total energy). We found that the associations between free sugar and non-free sugar intakes and CKD risk were more pronounced in participants with high genetically predicted gut microbial abundance. Furthermore, a significant interaction was observed between the genetically predicted gut microbial abundance and non-free sugar intake ( P for interaction = 0.04). Conclusion : A higher intake of free sugars was associated with an elevated risk of CKD, whereas a higher intake of non-free sugars was associated with a reduced risk of CKD. The impact of free sugar intake and non-free sugar intake may be modified by the gut microbial abundance.