Kidney Week

Abstract: TH-PO999

Effects of Body Mass Index on Rapid Kidney Function Decline: A Two-Sample Mendelian Randomization Study

Session Information

• CKD: Epidemiology, Risk Factors, and Prevention - 1
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Hu, Haofei, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China

Haofei Hu, MD

• Ye, Zhiming, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China

Zhiming Ye

Background

Observational studies have reported an association between body mass index (BMI) and a decline in renal function, but the causal relationship between BMI and renal function decline has not been established. The objective of the study was to use the two-sample Mendelian randomization (MR) approach to evaluate the causal impact of BMI on rapid renal function decline.

Methods

We obtained the instrumental variables for BMI from a meta-analysis of genome-wide association studies (GWAS) that included approximately 700,000 individuals of European descent. To obtain summary statistics data for rapid renal function decline, we used data from a previously published meta-analysis of GWAS that included over 270,000 individuals. Two criteria were used to determine the rapid renal function decline: a decline of 3 mL/min/1.73m²/year or more in estimated glomerular filtration rate (eGFR) ("Rapid3"), and a drop of 25% or more in eGFR and an eGFR below 60 mL/min/1.73m² at follow-up among individuals with eGFR of 60 mL/min/1.73m² or more at baseline (“CKDi25). We employed several filtering steps to select robust genetic instruments associated with BMI. Our primary analysis utilized the inverse variance weighted (IVW) method, with additional MR methods including weighted median, MR-Egger, and MR Pleiotropy RESidual Sum and Outlier test.

Results

We utilized a set of 491 single nucleotide polymorphisms (SNPs) as instrumental variables in this MR study. Our findings showed that genetically predicted higher BMI was significantly associated with an elevated risk of rapid renal function decline, as determined by the IVW method for CKDi25 [OR = 1.33, 95% CI = 1.22-1.44, P = 1.54 × 10^-11] and Rapid3 [OR = 1.15, 95% CI = 1.09-1.22, P = 7.99 × 10⁻⁷]. The results of both the MR Egger regression analysis and the weighted median method were consistent with the primary analysis. In addition, the effect estimate remained stable even after eliminating SNPs that were connected to confounding factors, and the "Leave-one-out" analysis validated the consistency of our findings. Notably, the absence of heterogeneity and directional pleiotropy was suggested by our results.

Conclusion

The results of the MR analysis suggest that there may be a causal relationship between BMI and a higher risk of renal function decline.

Funding

• Other NIH Support