Metabolism of intact PTH by isolated perfused kidney and liver from uremic rats

The metabolism of synthetic human intact PTH (1-84), 1,000 or 3 pmol/l, was studied in isolated perfused livers and in filtering and nonfiltering kidneys from normal rats and rats made chronically uremic by 5/6 nephrectomy. Clearances were measured by assays specific for intact PTH, and NH2-terminal, mid-molecule, and COOH-terminal iPTH. Release of PTH fragments was analyzed by HPLC. Clearance of the added intact PTH by the uremic kidneys was reduced by the same order of magnitude as GFR. Neither the uremic nor the normal kidneys released any iPTH fragments. No peritubular metabolism of intact PTH was found in the uremic nonfiltering kidneys. Clearance of intact PTH by uremic and control livers was not significantly different. The uremic and control livers released equal amounts of COOH-terminal iPTH fragments, but no NH2-terminal fragments. Thus, uremia per se did not influence the renal and hepatic metabolism of PTH.