Journal article
Parathyroid hormone and phosphorus overload in uremia: impact on cardiovascular system
Nephrology, dialysis, transplantation, Vol.27(4), pp.1437-1445
04/01/2012
DOI: 10.1093/ndt/gfr447
PMID: 21825304
Abstract
Background. Cardiac remodeling in uremia is characterized by left ventricular hypertrophy, interstitial fibrosis and microvascular disease. Cardiovascular disease is the leading cause of death in uremic patients, but coronary events alone are not the prevalent cause, sudden death and heart failure are. We studied the cardiac remodeling in experimental uremia, evaluating the isolated effect of parathyroid hormone (PTH) and phosphorus.
Methods. Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx); they also received vehicle (V) and PTH at normal (nPTH) or high (hPTH) doses. They were fed with a poor-phosphorus (pP) or rich-phosphorus (rP) diet and were divided into the following groups: 'Sham': G1 (V + normal-phosphorus diet (np)) and 'Nx + PTx': G2 (nPTH + pP), G3 (nPTH + rP), G4 (hPTH + pP) and G5 (hPTH + rP). After 8 weeks, biochemical analysis, myocardium morphometry and arteriolar morphological analysis were performed. In addition, using immunohistochemical analysis, we evaluated angiotensin II, alpha-actin, transforming growth factor-beta (TGF-beta) and nitrotyrosine, as well as fibroblast growth factor-23 (FGF-23), fibroblast growth factor receptor-1 (FGFR-1) and runt-related transcription factor-2 (Runx-2) expression.
Results. Nx animals presented higher serum creatinine levels as well as arterial hypertension. Higher PTH levels were associated with myocardial hypertrophy and fibrosis as well as a higher coronary lesion score. High PTH animals also presented a higher myocardial expression of TGF-beta, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of alpha-actin. Phosphorus overload was associated with higher serum FGF-23 levels and Runx-2, as well as myocardial hypertrophy. FGFR-1 was positive in the cardiomyocytes of all groups as well as in calcified coronaries of G4 and G5 whereas Runx-2 was positive in G3, G4 and G5.
Conclusion. In uremia, PTH and phosphorus overload are both independently associated with major changes related to the cardiac remodeling process, emphasizing the need for a better control of these factors in chronic kidney disease.
Details
- Title: Subtitle
- Parathyroid hormone and phosphorus overload in uremia: impact on cardiovascular system
- Creators
- Melani R. Custodio - Universidade de São PauloMarcia K. Koike - Universidade de São PauloKatia R. Neves - Universidade de São PauloLuciene M. dos Reis - Universidade de São PauloFabiana G. Graciolli - Universidade de São PauloCarolina L. Neves - Universidade de São PauloDaniella G. Batista - Universidade de São PauloAndrea O. Magalhaes - Universidade de São PauloPhilippe Hawlitschek - Universidade de São PauloIvone B. Oliveira - Universidade de São PauloWagner V. Dominguez - Universidade de São PauloRosa M. A. Moyses - Universidade de São PauloVanda Jorgetti - Universidade de São Paulo
- Resource Type
- Journal article
- Publication Details
- Nephrology, dialysis, transplantation, Vol.27(4), pp.1437-1445
- DOI
- 10.1093/ndt/gfr447
- PMID
- 21825304
- NLM abbreviation
- Nephrol Dial Transplant
- ISSN
- 0931-0509
- eISSN
- 1460-2385
- Publisher
- Oxford Univ Press
- Number of pages
- 9
- Grant note
- 01/01789-0; 06/52039-4 / 'Fundacao de Amparo a Pesquisa do Estado de Sao Paulo' (FAPESP, Foundation for the Support of Research in the state of Sao Paulo); Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
- Language
- English
- Date published
- 04/01/2012
- Academic Unit
- Anesthesia
- Record Identifier
- 9985090698202771
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