Metabolism of immunoreactive parathyroid hormone in the dog. The role of the kidney and the effects of chronic renal disease

Abstract

The role of the kidney in the metabolism of parathyroid hormone (PTH) was examined in the dog. Studies were performed in awake normal and uremic dogs after administration of bovine parathyroid hormone (b PTH) or synthetic amino terminal tetratricontapeptide of b PTH (syn b PTH 1-34). The renal clearance of immunoreactive PTH was determined from the product of renal plasma flow and the percent extraction of PTH immunoreactivity by the kidney. Blood levels of circulating immunoreactivity PTH were determined by radioimmunoassay. The normal dog kidney extracted 20±1% of the immunoreactive b PTH delivered to it, and renal clearance (RC) of immunoreactivity was 60 ml/min. When RC was compared to an estimate of total metabolic clearance (MCR) of immunoreactivity, it accounted for 61% of the total. Both MCR and RC were markedly decreased in dogs with chronic renal disease. However, the percent extraction of immunoreactivity PTH was unchanged in chronic renal disease, and the observed decrease in RC was due to changes in renal plasma flow. The largest portion of the reduction in total MCR was accounted for by the decrease in RC, and there was no compensation for the decrease in RC by extrarenal sites of PTH metabolism. Gel filtration of pooled serum samples from normal and chronic renal disease dogs demonstrated a rapid conversion of injected intact b PTH into immunologically detectable peptide fragments of both the carboxyl (C) and amino (N) terminal portion of the PTH molecule. The elution pattern of samples from dogs with renal disease demonstrated higher levels of each immunologically detected peptide and especially C terminal fragments throughout the time of study. Studies with the biologically active N terminal PTH fragments (syn b PTH 1-34) 27w14=effects demonstrated a higher renal extraction of 37±3% and a more rapid total MCR than was seen with b PTH. The effect of renal disease on the clearance rates of syn b PTH 1-34 were similar to those seen with b PTH except that there was a more marked decrease in extrarenal clearance of syn b PTH 1-34. Extrarenal syn b PTH 1-34 clearance was 133±9 ml/min in normals and 58±14 ml/min in dogs with renal disease. These studies indicate that the kidney plays an important role in the metabolism of PTH in vivo. They describe the impaired degradation of PTH seen in uremia, and they suggest that this may be a factor that contributes to the high levels of circulating immunoreactive PTH seen in chronic renal disease. They also suggest an effect of renal disease on PTH metabolism at sites other than the kidney.