Oxidized Low-Density Lipoprotein Predicts the Development of Renal Dysfunction in Atrial Fibrillation

Background/Aim: To investigate the role of oxidative stress (OS) in the development of chronic kidney disease (CKD) in atrial fibrillation (AF). Methods: We compared OS burden, determined at study inclusion as plasma concentrations of oxidized low-density lipoprotein (oxLDL), between stable AF patients (n = 256, mean age: 62.8 ± 9.3 years; 60.9% males) with preserved renal function, defined as an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2, and a matched control group in sinus rhythm (n = 138, mean age: 61.5 ± 11.2 years; 60.9% males). During the prospective follow-up of AF patients, we investigated the association and prognostic validity of oxLDL for CKD development, diagnosed as a sustained decline in eGFR to <60 ml/min/1.73 m2. Results: AF patients had a higher mean oxLDL (76.2 ± 21.7 U/l) compared to sinus rhythm controls (61.6 ± 13.1 U/l; p < 0.001). AF presence independently predicted increased oxLDL levels in the study cohort [β = 14.7; 95% confidence interval (CI), 10.7-18.7; p < 0.001]. Over a median 4-year follow-up, 19.9% of AF patients developed CKD. Adjusting for all clinical covariates, oxLDL (per tertile) was associated with a hazard ratio of 2.17 for CKD occurrence (95% CI, 1.40-3.35; p < 0.001). AF patients in the upper oxLDL tertile (≥88.7 U/l) had a 3.70-fold (95% CI, 1.55-8.81) higher risk for CKD compared to the lower oxLDL tertile (<67.0 U/l) patients (p < 0.001). oxLDL improved discriminative validity (c-statistic increment: 0.041, 95% CI, 0.007-0.075, p = 0.017), and increased the net reclassification and integrated discrimination for CKD risk by 12.4 and 6.0%, respectively (both p < 0.001). Conclusions: oxLDL is increased in AF patients compared to sinus rhythm controls. oxLDL has an independent association and an incremental predictive value that might complement clinical CKD risk assessment in AF patients following further research.