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

Autor: Martínez-Arias L; Unidad de Gestión Clínica de Metabolismo Óseo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Universidad de Oviedo, Oviedo, Spain., Panizo-García S; Unidad de Gestión Clínica de Metabolismo Óseo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Universidad de Oviedo, Oviedo, Spain., Martín-Vírgala J; Unidad de Gestión Clínica de Metabolismo Óseo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Universidad de Oviedo, Oviedo, Spain., Martín-Carro B; Unidad de Gestión Clínica de Metabolismo Óseo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Universidad de Oviedo, Oviedo, Spain., Fernández-Villabrille S; Unidad de Gestión Clínica de Metabolismo Óseo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Universidad de Oviedo, Oviedo, Spain., Avello-Llano N; Laboratorio de Medicina, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Spain., Miguel-Fernández D; Laboratorio de Medicina, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Spain., Ruíz Torres MP; Departamento de Biología de Sistemas, Unidad de Fisiología, Facultad de Medicina, Universidad de Alcalá de Henares, Retic REDinREN-ISCIII, Madrid, Spain., Cannata-Andía JB; Unidad de Gestión Clínica de Metabolismo Óseo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Universidad de Oviedo, Oviedo, Spain. Electronic address: cannata@hca.es., Carrillo-López N; Unidad de Gestión Clínica de Metabolismo Óseo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Universidad de Oviedo, Oviedo, Spain., Naves-Díaz M; Unidad de Gestión Clínica de Metabolismo Óseo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Universidad de Oviedo, Oviedo, Spain.
Jazyk: angličtina
Zdroj: Nefrologia [Nefrologia (Engl Ed)] 2021 Nov-Dec; Vol. 41 (6), pp. 640-651. Date of Electronic Publication: 2022 Jan 03.
DOI: 10.1016/j.nefroe.2021.12.004
Abstrakt: 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 µg/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.
(Copyright © 2021. Published by Elsevier España, S.L.U.)
Databáze: MEDLINE
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