Abstract MP30: Metabolomics Analyses Identified Factors Modifying the Association of Aspirin Use With Kidney Function

Abstract

Introduction: Uncontrolled high dose aspirin use impairs kidney function. Short-term low dose aspirin treatment has also been associated with kidney function in older patients. We aimed to evaluate the association of regular aspirin use with kidney function in middle-aged adults and to identify factors modifying the association. Methods: We performed cross-sectional analyses among 1,261 participants of the 2016 Bogalusa Heart Study (BHS) visit. Regular aspirin use was self-reported and confirmed by serum biomarker, salicyluric glucuronide . Aspirin users were categorized at the median of salicyluric glucuronide levels into low and high dose users. A total of 887 known metabolites were profiled from the serum. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi equation. We tested associations of aspirin use with eGFR and examined interactions of aspirin with serum metabolites on eGFR. Age, sex, race, education, smoking, drinking, physical activity, BMI, blood pressure, and fasting glucose were adjusted in all analyses. Results: The mean age of BHS participants was 48.2, and 133 (10.5%) were self-reported aspirin users. Serum salicyluric glucuronide level was significantly correlated with self-reported aspirin usage (P=2.00х10 -21 ). After adjusting for all covariables, mean eGFR for never, low dose, and high dose aspirin users were 92.9, 90.2, and 89.9 mL/min/1.73m 2 , respectively (P for trend=0.004). After Bonferroni correction, 28 metabolites modified the associations of aspirin use with eGFR (P<5.52х10 -5 ), of which, 26 increased the aspirin's nephrotoxicity effect, while behenoylsphingomyelin and tricosanoylsphingomyelin significantly attenuated the eGFR lowering effect of aspirin (Table). Conclusion: Aspirin use is associated with decreased eGFR among middle-aged adults, and this association was modified by dietary, gut microbiome, and biomarkers of kidney disease, cardiovascular disease, and cancer. The findings may help develop better use strategies for regular users.