Increased Thrombogenicity in Chronic Renal Failure in a Rat Model Induced by 5/6 Ablation/Infarction

Abnormalities in hemostasis and coagulation have been suggested in chronic renal failure (CRF). In this study, we compared processes of thrombus formation between rats with CRF and those with normal kidney function.

CRF was induced by 5/6 ablation/infarction of the kidneys in Sprague-Dawley rats, and surviving rats after 4 weeks were used. Ferric chloride (FeCl₃)-induced thrombosis in the carotid artery was induced to assess thrombus formation. Whole blood clot formation was evaluated using rotational thromboelastometry (ROTEM). Platelet aggregation was assessed with impedance platelet aggregometry.

FeCl₃-induced thrombus formation was initiated faster in the CRF group than in the control group (13.2±1.1 sec vs. 17.8±1.0 sec, p=0.027). On histological examination, the maximal diameters of thrombi were larger in the CRF group than in the control group (394.2±201.1 μm vs. 114.0±145.1 μm, p=0.039). In extrinsic pathway ROTEM, the CRF group showed faster clot initiation (clotting time, 59.0±7.3 sec vs. 72.8±5.0 sec, p=0.032) and increased clot growth kinetics (α angle, 84.8±0.2° vs. 82.0±0.6°, p=0.008), compared to the control group. Maximal platelet aggregation rate was higher in the CRF group than in the control group (58.2±0.2% vs. 44.6±1.2%, p=0.006).

Our study demonstrated that thrombogenicity is increased in rats with CRF. An activated extrinsic coagulation pathway may play an important role in increasing thrombogenicity in CRF.