Role of kidney in the catabolic clearance of human platelet antiheparin proteins from rat circulation

Abstract

Stimulated platelets release at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4) from which beta-thromboglobulin (beta TG) is derived. We have found previously marked elevation of LA-PF4/beta TG antigen in platelet poor plasma of patients with chronic renal failure, whereas levels of PF4 remained normal. Therefore, we examined the role of the kidneys in the metabolic clearance of LA-PF4/beta TG and PF4. The supernates of aggregates of thrombin-stimulated human platelets were injected into sham operated control rats, nephrectomized rats, and into rats with acute ureteral ligation. The disappearance of human LA-PF4/beta TG antigen and PF4 in rat plasma determined by specific radioimmunoassays followed biphasic exponential curves. The half-lives (t1/2) for the fast and slow components of LA-PF4 in control rats were 6.4 and 68.4 min. Nephrectomy significantly increased these times to 9.7 and 144 min, while ureteral ligation resulted in no significant change. Comparison of the level of LA-PF4/beta TG antigen and of creatinine in aorta and in renal vein showed 25%-30% extraction of these compounds by the kidney. Less than 0.1% of the total LA-PF4 antigen injected was recovered in the urine of control rats. In contrast to these results, the clearance of PF4 was not affected by nephrectomy. In conclusion: (1) functional renal tissue is necessary for normal clearance of LA- PF4/beta TG, but renal excretion does not play a major role in its elimination suggesting that the protein is catabolized by the kidney; and (2) catabolic clearance of PF4 does not depend on functioning kidney tissue.

Platelet activation and secretion in patients with major depression, thoracic aortic atherosclerosis, or renal dialysis treatment

“…With a t 1/2 of approximately 13 min, in comparison to β-TG's t 1/2 of 90 to 100 min [Dawes et al, 1978;Switalska et al, 1985], PF4 normally exists in plasma concentrations half that of β-TG [Flicker et al, 1982]. In concordance with this study, other investigators have noted relatively normal plasma concentrations of PF4 in patients with chronic renal failure [Guzzo et al, 1980], even after nephrectomy [Bastl et al, 1981], and within 24 hr after dialysis (despite an increase by 50-75% of both PF4 and β-TG during dialysis) [Cianciolo et al, 1999].…”