Experimental evidence for renal catabolism of fibrin fragment beta 15-42.
The elimination of labelled human fibrin fragment beta 15-42 from the circulation has been studied in an experimental rat model. When 125I beta 15-42 was injected as a bolus into a control group of rats, its elimination from the circulation could be fitted to a two compartment exponential model. A fast initial elimination had a t1/2 of less than 2 min and this was followed by a slower component with a calculated t1/2 of 135 min. The fast component was caused by equilibration of peptide throughout the intra and extra vascular spaces and the slow component reflected the action of catabolic processes once equilibration had been attained. Rats that had undergone bilateral nephrectomy eliminated significantly less of the labelled peptide than the control animals at a given time and the t1/2 of the slow component was prolonged, but not significantly, to 159 min. Rats with ligated ureters had statistically indistinguishable elimination curves from control rats. Examination of the heterogeneity of labelled peptide in plasma samples taken during the experiments by immunoprecipitation and by gel filtration revealed progressive extensive degradation in the control and ureteral ligated rats, but less degradation in nephrectomized rats. These results suggest that beta 15-42 is eliminated, in part, from the circulation by uptake and catabolism by the kidney. It is concluded that impaired renal function may results in elevated plasma levels of beta 15-42 antigen in human renal failure without the need for an increased rate of production of the peptide.
D000818:Animals; D004195:Disease Models, Animal; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism; D008657:Metabolic Clearance Rate; D009392:Nephrectomy; D010446:Peptide Fragments; D051381:Rats; D011919:Rats, Inbred Strains
D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C033786:fibrinogen Bbeta (15-42)