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Contribution of phosphorus and PTH to the development of cardiac hypertrophy and fibrosis in an experimental model of chronic renal failure.

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Title: Contribution of phosphorus and PTH to the development of cardiac hypertrophy and fibrosis in an experimental model of chronic renal failure.
Alternate Title: Contribución de fósforo y PTH al desarrollo de hipertrofia y fibrosis cardiaca en un modelo experimental de insuficiencia renal crónica.
Authors: Martínez-Arias, Laura1, Panizo-García, Sara1, Martín-Vírgala, Julia1, Martín-Carro, Beatriz1, Fernández-Villabrille, Sara1, Avello-Llano, Noelia2, Miguel-Fernández, Diego2, Ruiz Torres, María Piedad3, Cannata-Andía, Jorge B.1 cannata@hca.es, Carrillo-López, Natalia1, Naves-Díaz, Manuel1
Source: Nefrologia. Nov/Dec2021, Vol. 41 Issue 6, p640-651. 12p.
Subjects: CHRONIC kidney failure, CARDIAC hypertrophy, HEART fibrosis, HYPERPHOSPHATEMIA, PHOSPHORUS, HYPOPARATHYROIDISM, RENAL fibrosis
Abstract (English): Background and objective: Adequate serum phosphorus levels in patients with chronic kidney disease is essential for their clinical management. However, the control of hyperphosphatemia is difficult because is normally associated with increases in serum PTH. In the present study, the effects of hyperphosphatemia, in the presence of elevated and normal PTH, on cardiac inflammation, hypertrophy and fibrosis in an experimental renal failure model were analyzed. Materials and methods: 4 groups of rats were formed. Two groups underwent total parathyroidectomy (PTx). Rats with Ca <7.5 mg/dL and PTH < 50 pg/mL underwent 7/8 nephrectomy (CRF) and a subcutaneous pellet was placed that releases PTH 1-34 (5 µ/kg/day). One group received a diet with normal P (NP) (CRF + PTx + rPTH + NP group) and another with a high P diet (0.9% - HP) (CRF + PTx + rPTH + HP group). Other 2 groups that only had CRF received NP (CRF + NP) and HP (CRF + HP) diet. A SHAM group for nephrectomy and parathyroidectomy was also added. After 14 weeks the rats were sacrificed. Results: The groups with a diet high in phosphorus (CRF + H A and CRF + PTx + rPTH + HP) had a significant reduction in creatinine clearance and also in body weight with an increase in serum phosphorus regardless of parathyroidectomy, but not serum levels of calcium, FGF23 and calcitriol that were 2-3 times higher in the group with secondary hyperparathyroidism (CRF + HP). The diameter of the cardiomyocytes was greater in the CRF + HP group, while parathyroidectomy (CRF + PTx + rPTH + HP) significantly reduced them, despite the high and similar serum phosphorus values. TNF-α, Adam17 and cardiac fibrosis at the histological and molecular level showed a similar pattern with increases in the group with severe secondary hyperparathyroidism (CRF + HP). Conclusions: Hyperphosphatemia confirmed its importance in the genesis of secondary hyperparathyroidism, but also of kidney damage that was independent of PTH levels. However, inflammation, fibrosis, and cardiomyocyte growth were more closely related to PTH levels, since in the presence of similar severe hyperphosphatemia, parathyroidectomy reduced the values of inflammatory parameters, cardiac hypertrophy, and fibrosis. [ABSTRACT FROM AUTHOR]
Abstract (Spanish): Antecedentes y objetiuo:Mantener niveles adecuados de fósforo sérico en el paciente con enfermedad renal crónica es fundamental para su correcto manejo clínico. Sin embargo resulta difícil su control de forma aislada porque normalmente se asocian con aumentos séricos de PTH. En el presente estudio se analizaron los efectos de la hiperfosfatemia aislada, en presencia de PTH elevada y normal, sobre la inflamación, hipertrofia y fibrosis cardiaca en un modelo de insuficiencia renal experimental. Materiales y métodos: Se formaron 4 grupos de ratas. A dos grupos se les realizó paratiroidec- tomía total (PTx). A las ratas con Ca < 7,5 mg/dLy PTH<50pg/mL se les realizó nefrectomía 7/8 (IRC) y se les colocó un pellet subcutáneo que libera PTH 1-34 (5 |µg/kg/día). Un grupo recibió dieta con P normal (PN) (grupo IRC + PTx + rPTH + PN) y otro dieta con P alto (0,9%- PA) (grupo IRC + PTx + rPTH + PA). Otros 2 grupos que solo tenían IRC recibieron dieta PN (IRC + PN)y PA(IRC + PA). Se añadió también un grupo SHAM para nefrectomía y paratiroidec- tomía. Tras 14 semanas las ratas fueron sacrificadas. Resnltados: Los grupos con dieta alta en fósforo (IRC + PA e IRC + PTx + rPTH + PA) tuvieron una reducción significativa del aclaramiento de creatinina y también del peso corporal con un aumento del fósforo sérico independientemente de la paratiroidectomía, pero no así los niveles séricos de calcio, FGF23 y de calcitriol que fueron 2-3 veces superiores en el grupo con hiperparatiroidismo secundario (IRC + PA). El diámetro de los cardiomiocitos fue superior en el grupo IRC + PA, mientras la paratiroidectomía (IRC + PTx + rPTH + PA) los redujo significativamente, a pesar de los elevados y similares valores de fósforo sérico. El TNF- α, Adam17 y la fibrosis cardiaca a nivel histológico y molecular mostraron un patrón similar con aumentos en el grupo con hiperparatiroidismo secundario severo (IRC + PA). Conclnsiones.'La hiperfosfatemia confirmó su importancia en la génesis del hiperparatiroidismo secundario, pero también del daño renal que fue independiente de los niveles de PTH. Sin embargo, la inflamación, fibrosis y crecimiento de cardiomiocitos guardaron una mayor relación con los niveles de PTH ya que en presencia de hiperfosfatemia severa similar, la paratiroidectomía redujo los valores de los parámetros inflamatorios, de hipertrofia y fibrosis cardiaca. [ABSTRACT FROM AUTHOR]
Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Contribution of phosphorus and PTH to the development of cardiac hypertrophy and fibrosis in an experimental model of chronic renal failure.
– Name: TitleAlt
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  Data: Contribuci&#243;n de f&#243;sforo y PTH al desarrollo de hipertrofia y fibrosis cardiaca en un modelo experimental de insuficiencia renal cr&#243;nica.
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  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Mart&#237;nez-Arias%2C+Laura%22&quot;&gt;Mart&#237;nez-Arias, Laura&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Panizo-Garc&#237;a%2C+Sara%22&quot;&gt;Panizo-Garc&#237;a, Sara&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Mart&#237;n-V&#237;rgala%2C+Julia%22&quot;&gt;Mart&#237;n-V&#237;rgala, Julia&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Mart&#237;n-Carro%2C+Beatriz%22&quot;&gt;Mart&#237;n-Carro, Beatriz&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Fern&#225;ndez-Villabrille%2C+Sara%22&quot;&gt;Fern&#225;ndez-Villabrille, Sara&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Avello-Llano%2C+Noelia%22&quot;&gt;Avello-Llano, Noelia&lt;/searchLink&gt;&lt;relatesTo&gt;2&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Miguel-Fern&#225;ndez%2C+Diego%22&quot;&gt;Miguel-Fern&#225;ndez, Diego&lt;/searchLink&gt;&lt;relatesTo&gt;2&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Ruiz+Torres%2C+Mar&#237;a+Piedad%22&quot;&gt;Ruiz Torres, Mar&#237;a Piedad&lt;/searchLink&gt;&lt;relatesTo&gt;3&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Cannata-And&#237;a%2C+Jorge+B%2E%22&quot;&gt;Cannata-And&#237;a, Jorge B.&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;&lt;i&gt; cannata@hca.es&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Carrillo-L&#243;pez%2C+Natalia%22&quot;&gt;Carrillo-L&#243;pez, Natalia&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Naves-D&#237;az%2C+Manuel%22&quot;&gt;Naves-D&#237;az, Manuel&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22Nefrologia%22&quot;&gt;Nefrologia&lt;/searchLink&gt;. Nov/Dec2021, Vol. 41 Issue 6, p640-651. 12p.
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  Data: &lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22CHRONIC+kidney+failure%22&quot;&gt;CHRONIC kidney failure&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22CARDIAC+hypertrophy%22&quot;&gt;CARDIAC hypertrophy&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22HEART+fibrosis%22&quot;&gt;HEART fibrosis&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22HYPERPHOSPHATEMIA%22&quot;&gt;HYPERPHOSPHATEMIA&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22PHOSPHORUS%22&quot;&gt;PHOSPHORUS&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22HYPOPARATHYROIDISM%22&quot;&gt;HYPOPARATHYROIDISM&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22RENAL+fibrosis%22&quot;&gt;RENAL fibrosis&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract (English)
  Group: Ab
  Data: Background and objective: Adequate serum phosphorus levels in patients with chronic kidney disease is essential for their clinical management. However, the control of hyperphosphatemia is difficult because is normally associated with increases in serum PTH. In the present study, the effects of hyperphosphatemia, in the presence of elevated and normal PTH, on cardiac inflammation, hypertrophy and fibrosis in an experimental renal failure model were analyzed. Materials and methods: 4 groups of rats were formed. Two groups underwent total parathyroidectomy (PTx). Rats with Ca &lt;7.5 mg/dL and PTH &lt; 50 pg/mL underwent 7/8 nephrectomy (CRF) and a subcutaneous pellet was placed that releases PTH 1-34 (5 &#194;&#181;/kg/day). One group received a diet with normal P (NP) (CRF + PTx + rPTH + NP group) and another with a high P diet (0.9% - HP) (CRF + PTx + rPTH + HP group). Other 2 groups that only had CRF received NP (CRF + NP) and HP (CRF + HP) diet. A SHAM group for nephrectomy and parathyroidectomy was also added. After 14 weeks the rats were sacrificed. Results: The groups with a diet high in phosphorus (CRF + H A and CRF + PTx + rPTH + HP) had a significant reduction in creatinine clearance and also in body weight with an increase in serum phosphorus regardless of parathyroidectomy, but not serum levels of calcium, FGF23 and calcitriol that were 2-3 times higher in the group with secondary hyperparathyroidism (CRF + HP). The diameter of the cardiomyocytes was greater in the CRF + HP group, while parathyroidectomy (CRF + PTx + rPTH + HP) significantly reduced them, despite the high and similar serum phosphorus values. TNF-α, Adam17 and cardiac fibrosis at the histological and molecular level showed a similar pattern with increases in the group with severe secondary hyperparathyroidism (CRF + HP). Conclusions: Hyperphosphatemia confirmed its importance in the genesis of secondary hyperparathyroidism, but also of kidney damage that was independent of PTH levels. However, inflammation, fibrosis, and cardiomyocyte growth were more closely related to PTH levels, since in the presence of similar severe hyperphosphatemia, parathyroidectomy reduced the values of inflammatory parameters, cardiac hypertrophy, and fibrosis. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label: Abstract (Spanish)
  Group: Ab
  Data: Antecedentes y objetiuo:Mantener niveles adecuados de f&#243;sforo s&#233;rico en el paciente con enfermedad renal cr&#243;nica es fundamental para su correcto manejo cl&#237;nico. Sin embargo resulta dif&#237;cil su control de forma aislada porque normalmente se asocian con aumentos s&#233;ricos de PTH. En el presente estudio se analizaron los efectos de la hiperfosfatemia aislada, en presencia de PTH elevada y normal, sobre la inflamaci&#243;n, hipertrofia y fibrosis cardiaca en un modelo de insuficiencia renal experimental. Materiales y m&#233;todos: Se formaron 4 grupos de ratas. A dos grupos se les realiz&#243; paratiroidec- tom&#237;a total (PTx). A las ratas con Ca &lt; 7,5 mg/dLy PTH&lt;50pg/mL se les realiz&#243; nefrectom&#237;a 7/8 (IRC) y se les coloc&#243; un pellet subcut&#225;neo que libera PTH 1-34 (5 |&#194;&#181;g/kg/d&#237;a). Un grupo recibi&#243; dieta con P normal (PN) (grupo IRC + PTx + rPTH + PN) y otro dieta con P alto (0,9%- PA) (grupo IRC + PTx + rPTH + PA). Otros 2 grupos que solo ten&#237;an IRC recibieron dieta PN (IRC + PN)y PA(IRC + PA). Se a&#241;adi&#243; tambi&#233;n un grupo SHAM para nefrectom&#237;a y paratiroidec- tom&#237;a. Tras 14 semanas las ratas fueron sacrificadas. Resnltados: Los grupos con dieta alta en f&#243;sforo (IRC + PA e IRC + PTx + rPTH + PA) tuvieron una reducci&#243;n significativa del aclaramiento de creatinina y tambi&#233;n del peso corporal con un aumento del f&#243;sforo s&#233;rico independientemente de la paratiroidectom&#237;a, pero no as&#237; los niveles s&#233;ricos de calcio, FGF23 y de calcitriol que fueron 2-3 veces superiores en el grupo con hiperparatiroidismo secundario (IRC + PA). El di&#225;metro de los cardiomiocitos fue superior en el grupo IRC + PA, mientras la paratiroidectom&#237;a (IRC + PTx + rPTH + PA) los redujo significativamente, a pesar de los elevados y similares valores de f&#243;sforo s&#233;rico. El TNF- α, Adam17 y la fibrosis cardiaca a nivel histol&#243;gico y molecular mostraron un patr&#243;n similar con aumentos en el grupo con hiperparatiroidismo secundario severo (IRC + PA). Conclnsiones.&#39;La hiperfosfatemia confirm&#243; su importancia en la g&#233;nesis del hiperparatiroidismo secundario, pero tambi&#233;n del da&#241;o renal que fue independiente de los niveles de PTH. Sin embargo, la inflamaci&#243;n, fibrosis y crecimiento de cardiomiocitos guardaron una mayor relaci&#243;n con los niveles de PTH ya que en presencia de hiperfosfatemia severa similar, la paratiroidectom&#237;a redujo los valores de los par&#225;metros inflamatorios, de hipertrofia y fibrosis cardiaca. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: &lt;i&gt;Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1016/j.nefroe.2021.12.004
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      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 12
        StartPage: 640
    Subjects:
      – SubjectFull: CHRONIC kidney failure
        Type: general
      – SubjectFull: CARDIAC hypertrophy
        Type: general
      – SubjectFull: HEART fibrosis
        Type: general
      – SubjectFull: HYPERPHOSPHATEMIA
        Type: general
      – SubjectFull: PHOSPHORUS
        Type: general
      – SubjectFull: HYPOPARATHYROIDISM
        Type: general
      – SubjectFull: RENAL fibrosis
        Type: general
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      – TitleFull: Contribution of phosphorus and PTH to the development of cardiac hypertrophy and fibrosis in an experimental model of chronic renal failure.
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            – D: 01
              M: 11
              Text: Nov/Dec2021
              Type: published
              Y: 2021
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