Photo Credit: Rasi Bhadramani

The following is a summary of “Genetically predicted frailty index and risk of chronic kidney disease” published in the September 2024 issue of Nephrology by Chen et al.

Previous research has shown a connection between frailty and chronic kidney disease (CKD), but whether frailty directly causes CKD remains unclear. This study aims to explore if there is a causal relationship between the frailty index and CKD.

Researchers conducted a retrospective study to determine if the frailty index is causally linked to CKD using genome-wide association study (GWAS) data. 

They obtained GWAS data for frailty and CKD from the FinnGen R5 dataset, with a total sample size of 216,743 (3,902 cases, 212,841 controls). A two-sample Mendelian randomization (MR) analysis used inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. Multivariable MR analysis (MVMR) was also done to adjust for confounders. 

The results showed that 14 single nucleotide polymorphisms (SNPs) were identified as suitable instrumental variables. The IVW method found a causal link between frailty index and CKD (beta = 1.270, 95% CI: 0.608 to 1.931, P<0.001). MR-Egger also showed a causal association (beta=3.612; 95% CI: 0.805 to 6.419, P=0.027), and pleiotropy was unlikely to bias the results (intercept= -0.053; P=0.119). The weighted median approach (beta = 1.148, 95% CI: 0.278 to 2.019; P=0.011) and the weighted mode method (beta = 2.194; 95% CI: 0.598 to 3.790; P=0.018) supported the causal link. Cochran’s Q test and funnel plot suggested no directional pleiotropy. The MVMR analysis confirmed the causal association even after adjusting for factors like body-mass index, inflammatory bowel disease, waist-hip ratio, and C-reactive protein. 

Investigators concluded that frailty is causally linked to CKD based on genetic evidence. This finding strengthens the understanding of how frailty might contribute to CKD from a genetic perspective.

Source: nature.com/articles/s41598-024-71881-7