Abnormal skeletal response to parathyroid hormone in dogs with chronic uremia

The release of cyclic AMP from bone in response to stimulation with PTH 1-34 was examined in 20 dogs with long-term chronic renal failure (CRF) produced by unilateral nephrectomy and contralateral partial renal artery ligation. After 9 to 15 months of uremia, the tibiae were removed and perfused in vitro. Seven dogs with CRF served as controls, 7 dogs with CRF were treated with 24,25(OH)2D3 - 2.5 micrograms per day, and 6 CRF dogs underwent thyroparathyroidectomy (TPTX) 42 h before they were sacrificed. The release of cyclic AMP from bone in response to PTH 1-34 in the CRF dogs was severely reduced compared to the response observed in 7 dogs with normal renal function (net accumulation of cyclic AMP release 86 +/- 8.5 versus 426 +/- 59.0 pmol/30 min). Long-term treatment of uremic dogs with 24,25(OH)2D3 had no effect on the release of cyclic AMP by bone. However, the release of cyclic AMP was restored to normal levels in the CRF dogs that underwent thyroparathyroidectomy. All CRF dogs had secondary hyperparathyroidism and the fact that TPTX returned the cyclic AMP response to normal values suggests that desensitization to PTH of the adenylate cyclase system of bone exists in chronic uremia.