RESUMO
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, α-actin, transforming growth factor-beta (TGF-ß) 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-ß, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of α-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.
Assuntos
Doenças Cardiovasculares/etiologia , Fibrose/etiologia , Hormônio Paratireóideo/metabolismo , Fósforo na Dieta/metabolismo , Uremia/complicações , Uremia/fisiopatologia , Animais , Biomarcadores/metabolismo , Doenças Cardiovasculares/patologia , Fibrose/patologia , Técnicas Imunoenzimáticas , Masculino , Nefrectomia/efeitos adversos , Hormônio Paratireóideo/administração & dosagem , Paratireoidectomia/efeitos adversos , Fósforo na Dieta/administração & dosagem , Ratos , Ratos WistarRESUMO
Bone disease is a common disorder of bone remodeling and mineral metabolism, which affects patients with chronic kidney disease. Minor changes in the serum level of a given mineral can trigger compensatory mechanisms, making it difficult to evaluate the role of mineral disturbances in isolation. The objective of this study was to determine the isolated effects that phosphate and parathyroid hormone (PTH) have on bone tissue in rats. Male Wistar rats were subjected to parathyroidectomy and 5/6 nephrectomy or were sham-operated. Rats were fed diets in which the phosphate content was low, normal, or high. Some rats received infusion of PTH at a physiological rate, some received infusion of PTH at a supraphysiological rate, and some received infusion of vehicle only. All nephrectomized rats developed moderate renal failure. High phosphate intake decreased bone volume, and this effect was more pronounced in animals with dietary phosphate overload that received PTH infusion at a physiological rate. Phosphate overload induced hyperphosphatemia, hypocalcemia, and changes in bone microarchitecture. PTH at a supraphysiological rate minimized the phosphate-induced osteopenia. These data indicate that the management of uremia requires proper control of dietary phosphate, together with PTH adjustment, in order to ensure adequate bone remodeling.
Assuntos
Osso e Ossos/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Animais , Doenças Ósseas Metabólicas , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Humanos , Nefropatias , Falência Renal Crônica/sangue , Masculino , Glândulas Paratireoides/efeitos dos fármacos , Glândulas Paratireoides/metabolismo , Hormônio Paratireóideo/sangue , Paratireoidectomia , Fosfatos/sangue , Ratos , Ratos Wistar , Insuficiência Renal/metabolismo , Uremia/metabolismoRESUMO
O polimorfismo (I/D) inserçäo/deleçäo do gene da enzima de conversäo da angiotensina (ECA) se correlaciona com a concentraçäo celular e circulante da ECA. Indivíduos com genótipo D/D têm concentraçäo circulante de ECA mais elevada de que aqueles com genótipo I/I. O genótipo I/D tem concentraçäo intermediária. O genótipo D/D tem sido associado com o desenvolvimento e/ou progressäo da doença renal e como fator de risco para doença cardiovascular, podendo ser um marcador de hipertrofia ventricular esquerda (HVE). Este trabalho avalia o polimorfismo do gene da ECA por técnica de PCR em 23 pacientes hemodialisados com IRC terminal de diversas etiologias e também sua associaçäo com HVE. Foram estudados 12 pacientes do sexo masculino e 11 do sexo feminino, com idade de 33,9 ñ 16,0 anos. A distribuiçäo dos genótipos da ECA foi comparada com 20 indivíduos saudáveis, sendo 11 do sexo masculino e 9 do sexo feminino, com idade de 31,4 ñ 8,0 anos. A distribuiçäo do genótipo da ECA nos pacientes renais crônicos foi de 60,9 por cento I/D, 34,8 por cento D/D e 4,3 por cento I/I. No grupo-controle foi de 6,0 por cento I/D, 25,0 por cento D/D e 15,0 por cento I/I. Näo houve diferença estatisticamente significante na distribuiçäo do genótipo entre os grupos (P>0,05). Todos os pacientes apresentavam HVE e näo houve diferença estatística significante no índice de massa do ventrículo esquerdo entre os pacientes com genótipo I/D ou D/D. Concluímos que na populaçäo estudada de pacientes com IRC terminal näo houve associaçäo entre o genótipo D/D da ECA e a presença de nefropatia crônica ou hipertrofia ventricular esquerda.