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, undetectable in the plasma in health but elevated in certain disease states such as medullary thyroid cancer, and potentially causes symptoms. The kidney is a major site of and influence on the clearance of exogenously 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 patients, CGRP was not detected in plasma either before or after haemodialysis. In sheep, before and after bilateral nephrectomy, there was an approximate halving of plasma clearance and doubling of the circulating half-life of infused CGRP. This reduction in clearance was greater than that which could be accounted for by the reduction in degradation by renal substance alone. This renal influence on extra-renal CGRP metabolism 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 influences the extra-renal metabolism of CGRP remains obscure.
Rubinstein
C
C
Department of Surgery, University of Melbourne, Austin Hospital, Victoria, Australia.
Fletcher
D R
DR
Shulkes
A
A
Hardy
K J
KJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D009392:Nephrectomy; D006435:Renal Dialysis; D012756:Sheep
D015740:Calcitonin Gene-Related Peptide