Ogata, Hiroaki and Ritz, Eberhard and Odoni, Giulio and Amann, Kerstin and Orth, Stephan R. (2003) Beneficial effects of calcimimetics on progression of renal failure and cardiovascular risk factors. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 14 (4). pp. 959-967. ISSN 1046-6673, 1533-3450
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In renal failure, parathyroid hormone (PTH) is not only involved in the genesis of disturbed calcium/phosphate metabolism and ostitis fibrosa; it is also a permissive factor in the genesis of hypertension, cardiovascular damage, and dyslipidemia. The allosteric activator of the calcium sensing receptor NPSR-568 (R-568) has been shown to reduce the serum intact PTH (iPTH) concentration in uremic rats. It was the purpose of this study in subtotally nephrectomized (SNX) rats to compare pharmacologic abrogation of secondary hyperparathyroidism by R-568 with parathyroidectomy (PTX). The effects on progression of renal failure, BP, and lipid and structural parameters of kidney and heart were studied. Four groups of male SD-rats were studied: (1) sham-operated + vehicle-treated rats (controls); (2) SNX + vehicle-treated rats (SNX); (3) parathyroidectomized SNX + vehicle-treated rats (SNX+PTX); and (4) SNX + calcimimetic R-568-treated rats (SNX+R-568). R-568 (50 mumol/kg per d) was administered by gavage. Eight weeks after SNX, serum creatinine concentration, urinary albumin excretion, betaP, and serum LDL-cholesterol concentration were significantly lower in both R-568-treated and parathyroidectomized SNX compared with vehicle-treated SNX. In addition, structural abnormalities of the kidney (glomerulosclerosis, tubulointerstitial changes) and the heart (interstitial fibrosis, capillary length density, arteriolar wall thickness) were significantly less pronounced than in vehicle-treated SNX. It is concluded that in experimental renal failure abrogation of hyperparathyroidism by administration of a calcimimetic or PTX similarly attenuates progression of renal failure. Furthermore, it interferes with the development of cardiovascular risk factors and cardiac remodeling.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HORMONE-RELATED PROTEIN; CALCIUM-SENSING RECEPTOR; PARATHYROID-HORMONE; SECONDARY HYPERPARATHYROIDISM; BLOOD-PRESSURE; UREMIC RATS; HEMODIALYSIS-PATIENTS; VITAMIN-D; METABOLISM; SECRETION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Sep 2021 09:19 |
| Last Modified: | 15 Sep 2021 09:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39169 |
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