O40 TELOMERE LENGTH AS A BIOMARKER FOR KIDNEY HEALTH: EVIDENCE FROM A MENDELIAN RANDOMISATION STUDY

Background and Objective: Chronic kidney disease (CKD) is a significant public health challenge, often progressing undetected until advanced stages. Early detection through biomarkers can enhance CKD management and improve patient outcomes. Previous studies suggested a link between telomeres and kidney health, but these results were inconsistent. This study aims to clarify the association between telomere length, kidney function and disease, and assess its causality using Mendelian randomisation (MR). Methods: Using the UK Biobank data, we examined the relationship between leukocyte telomere length (LTL) and kidney health. We performed multiple linear and logistic regression analyses using estimated glomerular filtration rate (eGFR) measures and reported kidney disease diagnoses, adjusting for age, sex, white blood cell count, body mass index, and hypertension. The causality of associations was tested using MR with established genetic instruments. Results: 338,143 participants were included in our analysis. The cohort had an average age of 56.52 years, with 54.41% being females. LTL was associated with eGFR from serum creatinine (eGFRcrea, beta = 0.001, p <0.01), serum cystatin C (eGFRcys, beta = 0.004, p <0.0001), and their combination (eGFRcreacys, beta = 0.003, p <0.0001). Additionally, longer LTL was associated with reduced odds of CKD (OR = 0.94 [95% CI 0.93-0.96], p <0.0001). Significant associations were also observed between LTL and acute renal failure (OR = 0.95 [95% CI 0.93-0.97], p <0.0001), and hypertensive kidney disease (OR = 0.91 [95% CI 0.86-0.96], p <0.001). MR analysis supported a causal effect of LTL on eGFRcrea (Effect size = 0.006, Bonferroni corrected p = 0.04). However, no causal effect was observed between LTL and CKD or other kidney diseases. Bi-directional MR analysis revealed that the relationship between LTL and kidney function is unidirectional. Conclusions: Longer LTL correlates with better kidney function and reduced kidney disease risk. MR findings suggest a potential causal relationship between LTL and kidney function, highlighting telomeres as promising biomarkers for early detection of CKD.