THE ROLE OF THE KIDNEY IN THE CLEARANCE OF CALCITONIN-GENE-RELATED PEPTIDE (CGRP)

Calcitonin gene-related peptide (CGRP) is a 37 amino-acid peptide, und etectable in the plasma in health but elevated in certain disease stat es such as medullary thyroid cancer, and potentially causes symptoms. The kidney is a major site of and influence on the clearance of exogen ously infused CGRP. As CGRP might cause symptoms in renal dysfunction, this study was performed to determine the clearance of CGRP in humans and animals with altered renal function. In chronic renal failure pat ients, CGRP was not detected in plasma either before or after haemodia lysis. In sheep, before and after bilateral nephrectomy, there was an approximate halving of plasma clearance and doubling of the circulatin g half-life of infused CGRP. This reduction in clearance was greater t han that which could be accounted for by the reduction in degradation by renal substance alone. This renal influence on extra-renal CGRP met abolism was not due to the renal production of a circulating peptidase as evidenced by the absence of such peptidase in the plasma of normal and anephric sheep. Further, severity of uraemia had no influence on the extra-renal metabolism. The mechanism by which the kidney influenc es the extra-renal metabolism of CGRP remains obscure.