Targeting Proteins—in-Silico, In-Vitro, and In-Vivo Evidence

Background: Mechanisms by which chronic kidney disease (CKD) influences fibrin clot properties in atrial fibrillation (AF) remain ill-defined. We aimed to investigate the effects of AF and CKD on fibrin clot properties and lipoproteins, and determine the relationship between these factors. Methods: Prospective cross-sectional study of patients recruited from cardiology services in Liverpool between September 2019 and October 2021. Primary groups consisted of anticoagulated AF patients with and without CKD in a 1:1 ratio. Control group comprised anticoagulated patients without AF or CKD. Fibrin clot properties were analysed using turbidity and permeation assays. Detailed lipoprotein characteristics, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL and oxidised LDL, were measured. Results: Fifty-six anticoagulated patients were enrolled (median age 72.5; 34% female); 46 with AF (23 with CKD and 23 without CKD) and 10 controls. AF was associated with changes in three indices of fibrin clot properties using PTT (T_lag 314 vs. 358 s, p = 0.047; Abs_peak 0.153 vs. 0.111 units, p = 0.031; T_lysis50% 884 vs. 280 s, p = 0.047) and thrombin reagents (T_lag 170 vs. 132 s, p = 0.031; T_max 590 vs. 462 s, p = 0.047; T_peak50% 406 vs. 220 s, p = 0.005) while the concomitant presence of CKD led to changes in fibrin clot properties using kaolin (T_lag 1072 vs. 1640 s, p = 0.003; T_max 1458 vs. 1962 s, p = 0.005; T_peak50% 1294 vs. 2046, p = 0.008) and PPP reagents (T_lag 566 vs. 748 s, p = 0.044). Neither of these conditions were associated with changes in fibrin clot permeability. Deteriorating eGFR was significantly correlated to the speed of clot formation, and CKD was independently associated with unfavourable clot properties (T_lag −778, p = 0.002; T_max −867, p = 0.004; T_peak50% −853, p = 0.004 with kaolin reagent). AF alone was not associated with changes in lipoprotein distribution while AF patients with CKD had lower total cholesterol, LDL-C and small dense LDL due to the presence of other risk factors. No significant relationship was observed between fibrin clot properties and lipoprotein distribution. Conclusions: There are important changes that occur in fibrin clot properties with AF and CKD that may account for the increased risk of thromboembolic complications. However, these changes in fibrin clot properties were not attributable to alterations in lipoprotein distribution. Full article