title: High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats.
abstract: Although disorders of mineral metabolism and skeletal muscle are common in chronic kidney disease (CKD), their potential relationship remains unexplored. Elevations in plasma phosphate, parathyroid hormone, and fibroblastic growth factor 23 together with decreased calcitriol levels are common features of CKD. High-phosphate intake is a major contributor to progression of CKD. This study was primarily aimed to determine the influence of high-phosphate intake on muscle and to investigate whether calcitriol supplementation counteracts negative skeletal muscle changes associated with long-term uremia. Proportions and metabolic and morphological features of myosin-based muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of uremic rats (5/6 nephrectomy, Nx) and compared with sham-operated (So) controls. Three groups of Nx rats received either a standard diet (0.6% phosphorus, Nx-Sd), or a high-phosphorus diet (0.9% phosphorus, Nx-Pho), or a high-phosphorus diet plus calcitriol (10 ng/kg 3 day/wk ip, Nx-Pho + Cal) for 12 wk. Two groups of So rats received either a standard diet or a high-phosphorus diet (So-Pho) over the same period. A multivariate analysis encompassing all fiber-type characteristics indicated that Nx-Pho + Cal rats displayed skeletal muscle phenotypes intermediate between Nx-Pho and So-Pho rats and that uremia-induced skeletal muscle changes were of greater magnitude in Nx-Pho than in Nx-Sd rats. In uremic rats, treatment with calcitriol preserved fiber-type composition, cross-sectional size, myonuclear domain size, oxidative capacity, and capillarity of muscle fibers. These data demonstrate that a high-phosphorus diet potentiates and low-dose calcitriol attenuates adverse skeletal muscle changes in long-term uremic rats.
authors: Laboratory of Muscular Biopathology, Department of Comparative Anatomy and Pathological Anatomy, Faculty of Veterinary Sciences, University of Cordoba, Cordoba, Spain; Departamento de Ciencias Biomédicas, Facultad de Ciencias Veterinarias, Universidad Central de Venezuela, Maracay, Venezuela; and.
authors: Luz M
authors: LM
authors: Acevedo
authors: Departament of Animal Medicine and Surgery, University of Cordoba, Cordoba, Spain;
authors: Ignacio
authors: I
authors: López
authors: Departament of Animal Medicine and Surgery, University of Cordoba, Cordoba, Spain; Escuela de Medicina Veterinaria, Universidad Nacional Autónoma de Nicaragua, León, Nicaragua.
authors: Alan
authors: A
authors: Peralta-Ramírez
authors: Departament of Animal Medicine and Surgery, University of Cordoba, Cordoba, Spain;
authors: Carmen
authors: C
authors: Pineda
authors: Laboratory of Muscular Biopathology, Department of Comparative Anatomy and Pathological Anatomy, Faculty of Veterinary Sciences, University of Cordoba, Cordoba, Spain;
authors: Verónica E
authors: VE
authors: Chamizo
authors: Unidad de Investigación y Servicio de Nefrología (Ren in Ren), Instituto Sanitario de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain;
authors: Mariano
authors: M
authors: Rodríguez
authors: Departament of Animal Medicine and Surgery, University of Cordoba, Cordoba, Spain;
authors: Escolástico
authors: E
authors: Aguilera-Tejero
authors: Laboratory of Muscular Biopathology, Department of Comparative Anatomy and Pathological Anatomy, Faculty of Veterinary Sciences, University of Cordoba, Cordoba, Spain; an1lorij@uco.es.
authors: José-Luis L
authors: JL
authors: Rivero
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003430:Cross-Sectional Studies; D004032:Diet; D005260:Female; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010758:Phosphorus / Q000494:pharmacology*; D051381:Rats; D014511:Uremia / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D010281:Parathyroid Hormone; D010758:Phosphorus; D002117:Calcitriol; D002118:Calcium
keywords: active vitamin D; chronic renal failure; muscle fiber type; phosphorus; secondary hyperparathyroidism