 |
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
|
||||
| 2007 JASN IMPACT FACTOR 7.111 | HOME AUTHOR INFO EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP | |||
| CURRENT ISSUE | ARCHIVES | JASN Express | ONLINE SUBMISSION | |
*Department of Internal Medicine, University of Heidelberg, Heidelberg; Department of Pathology, University Erlangen-Nürnberg, Erlangen; Dialysis Centre Schwandorf, Schwandorf/Klinik für Inner Medizin II, University of Regensburg, Regensburg, Germany
Correspondence to Dr. Stephan R. Orth, Dialysezentrum Schwandorf, Marktplatz 32, D-92421 Schwandorf, Germany. Phone: 49-9431-71520; Fax: 49-9431-715240; E-mail: stephan.orth{at}gmx.net
ABSTRACT. 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 µmol/kg per d) was administered by gavage. Eight weeks after SNX, serum creatinine concentration, urinary albumin excretion, BP, 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.
E-mail: stephan.orth@gmx.net
This article has been cited by other articles:
 |
|
 |
|
  S. Smajilovic and J. Tfelt-Hansen Novel Role of the Calcium-Sensing Receptor in Blood Pressure Modulation Hypertension, December 1, 2008; 52(6): 994 - 1000. [Full Text] [PDF]
|
|
|
|
 |
|
 M.-u. Alam, J. P. Kirton, F. L. Wilkinson, E. Towers, S. Sinha, M. Rouhi, T. N. Vizard, A. P. Sage, D. Martin, D. T. Ward, et al. Calcification is associated with loss of functional calcium-sensing receptor in vascular smooth muscle cells Cardiovasc Res, November 6, 2008; (2008) cvn279v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Koleganova, G. Piecha, E. Ritz, and M.-L. Gross Calcitriol ameliorates capillary deficit and fibrosis of the heart in subtotally nephrectomized rats Nephrol. Dial. Transplant., October 1, 2008; (2008) gfn549v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ogata, M. Mizobuchi, F. Koiwa, E. Kinugasa, and T. Akizawa Clinical significance of parathyroid intervention on CKD-MBD management NDT Plus, August 1, 2008; 1(suppl_3): iii9 - iii13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Piecha, G. Kokeny, K. Nakagawa, N. Koleganova, A. Geldyyev, I. Berger, E. Ritz, C. P. Schmitt, and M.-L. Gross Calcimimetic R-568 or calcitriol: equally beneficial on progression of renal damage in subtotally nephrectomized rats Am J Physiol Renal Physiol, April 1, 2008; 294(4): F748 - F757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Fryer, J. A. Segreti, D. L. Widomski, P. H. Franklin, P. N. Banfor, K. A. Koch, M. Nakane, J. R. Wu-Wong, B. F. Cox, and G. A. Reinhart Systemic Activation of the Calcium Sensing Receptor Produces Acute Effects on Vascular Tone and Circulatory Function in Uremic and Normal Rats: Focus on Central versus Peripheral Control of Vascular Tone and Blood Pressure by Cinacalcet J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 217 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fliser, B. Kollerits, U. Neyer, D. P. Ankerst, K. Lhotta, A. Lingenhel, E. Ritz, F. Kronenberg, and for the MMKD Study Group Fibroblast Growth Factor 23 (FGF23) Predicts Progression of Chronic Kidney Disease: The Mild to Moderate Kidney Disease (MMKD) Study J. Am. Soc. Nephrol., September 1, 2007; 18(9): 2600 - 2608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Smajilovic and J. Tfelt-Hansen Calcium acts as a first messenger through the calcium-sensing receptor in the cardiovascular system Cardiovasc Res, August 1, 2007; 75(3): 457 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Drueke, D. Martin, and M. Rodriguez Can calcimimetics inhibit parathyroid hyperplasia? Evidence from preclinical studies Nephrol. Dial. Transplant., July 1, 2007; 22(7): 1828 - 1839. [Full Text] [PDF]
|
|
|
|
|
|
G. Rashid, J. Bernheim, J. Green, and S. Benchetrit Cardiovascular Events and Parathyroid Hormone--Suggestion of a Further Link J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1023 - 1026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mizobuchi, H. Ogata, I. Hatamura, F. Koiwa, F. Saji, K. Shiizaki, S. Negi, E. Kinugasa, A. Ooshima, S. Koshikawa, et al. Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism Nephrol. Dial. Transplant., April 1, 2006; 21(4): 911 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Schmitt, T. Odenwald, and E. Ritz Calcium, Calcium Regulatory Hormones, and Calcimimetics: Impact on Cardiovascular Mortality J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S78 - S80. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Odenwald, K. Nakagawa, C. Hadtstein, F. Roesch, P. Gohlke, E. Ritz, F. Schaefer, and C. P. Schmitt Acute Blood Pressure Effects and Chronic Hypotensive Action of Calcimimetics in Uremic Rats J. Am. Soc. Nephrol., March 1, 2006; 17(3): 655 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Evenepoel, K. Claes, D. Kuypers, B. Maes, and Y. Vanrenterghem Impact of parathyroidectomy on renal graft function, blood pressure and serum lipids in kidney transplant recipients: a single centre study Nephrol. Dial. Transplant., August 1, 2005; 20(8): 1714 - 1720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rodriguez, E. Nemeth, and D. Martin The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism Am J Physiol Renal Physiol, February 1, 2005; 288(2): F253 - F264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S Joy, A. V Kshirsagar, and N. Franceschini Calcimimetics and the Treatment of Primary and Secondary Hyperparathyroidism Ann. Pharmacother., November 1, 2004; 38(11): 1871 - 1880. [Abstract] [Full Text] [PDF]
|
|
|
HOME
CURRENT ISSUE
ARCHIVES
JASN Express
ONLINE SUBMISSION
AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP |
Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673
