Abstract
This study aims to investigate the association and causality between osteoarthritis (OA) and chronic kidney disease (CKD) using data from the National Health and Nutrition Examination Survey (NHANES) and Mendelian Randomization (MR) analysis. Participants with OA, urinary albumin, urinary creatinine, urinary albumin-to-creatinine ratio (UACR), blood creatinine, and estimated glomerular filtration rate (eGFR) were selected from NHANES. CKD was calculated using the CKD-EPI equation, and logistic regression assessed by the OA-CKD association. A two-sample MR analysis was conducted using Genome-wide association studies (GWAS) data for OA, hip OA (HOA), knee OA (KOA), acute renal failure (ARF), chronic renal failure (CRF), cystatin C, serum creatinine (eGFRcrea), and microalbuminuria. The inverse variance weighted (IVW) method was used, with heterogeneity, sensitivity, and pleiotropy assessments. The cross-sectional analysis showed a significant positive association between OA and CKD [unadjusted OR: 2.398 (95% CI: 2.176-2.643), p < 0.001], which persisted after adjustment for demographic factors, socioeconomic status, lifestyle factors, and medical history [adjusted OR: 1.161 (95% CI: 1.029-1.310), p = 0.015]. The MR analysis revealed no significant causal relationship between overall OA and renal function markers but found a significant genetic association between HOA and cystatin C [IVW p = 0.0014, OR = 1.02, 95% CI: 1.01-1.03], and between KOA and cystatin C [IVW p < 0.0001, OR = 1.06, 95% CI: 1.04-1.08]. Our study indicates that HOA and KOA are risk factors for renal function injury, providing new insights for clinical OA management.