Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms

Abstract In chronic kidney disease (CKD), high serum phosphate concentration is associated with cardiovascular disease and deterioration in renal function. In early CKD, the serum phosphate concentration is normal due to increased fractional excretion of phosphate. Our premise was that high phosphat...

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Autores principales:	Rafael Santamaría, Juan M. Díaz-Tocados, M. Victoria Pendón-Ruiz de Mier, Ana Robles, M. Dolores Salmerón-Rodríguez, Erena Ruiz, Noemi Vergara, Escolástico Aguilera-Tejero, Ana Raya, Rosa Ortega, Arnold Felsenfeld, Juan R. Muñoz-Castañeda, Alejandro Martín-Malo, Pedro Aljama, Mariano Rodríguez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Klotho Expression High Phosphate Concentrations Overt Proteinuria Mangiferin Excessive Phosphaturia Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3a9044172f1e4892a96027f03d91d2fe
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spelling	oai:doaj.org-article:3a9044172f1e4892a96027f03d91d2fe2021-12-02T15:08:42ZIncreased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms10.1038/s41598-018-32065-22045-2322https://doaj.org/article/3a9044172f1e4892a96027f03d91d2fe2018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32065-2https://doaj.org/toc/2045-2322Abstract In chronic kidney disease (CKD), high serum phosphate concentration is associated with cardiovascular disease and deterioration in renal function. In early CKD, the serum phosphate concentration is normal due to increased fractional excretion of phosphate. Our premise was that high phosphate intake even in patients with early CKD would result in an excessive load of phosphate causing tubular injury and accelerating renal function deterioration. In CKD 2–3 patients, we evaluated whether increased phosphaturia accelerates CKD progression. To have a uniform group of patients with early CKD, 95 patients with metabolic syndrome without overt proteinuria were followed for 2.7 ± 1.6 years. The median decline in eGFR was 0.50 ml/min/1.73 m2/year. Patients with a more rapid decrease in eGFR had greater phosphaturia. Moreover, the rate of decrease in eGFR inversely correlated with the degree of phosphaturia. Additionally, phosphaturia independently predicted renal function deterioration. In heminephrectomized rats, a high phosphate diet increased phosphaturia resulting in renal tubular damage associated with inflammation, oxidative stress and low klotho expression. Moreover, in rats with hyperphosphatemia and metabolic syndrome antioxidant treatment resulted in attenuation of renal lesions. In HEK-293 cells, high phosphate promoted oxidative stress while melatonin administration reduced ROS generation. Our findings suggest that phosphate loading in early CKD, results in renal damage and a more rapid decrease in renal function due to renal tubular injury.Rafael SantamaríaJuan M. Díaz-TocadosM. Victoria Pendón-Ruiz de MierAna RoblesM. Dolores Salmerón-RodríguezErena RuizNoemi VergaraEscolástico Aguilera-TejeroAna RayaRosa OrtegaArnold FelsenfeldJuan R. Muñoz-CastañedaAlejandro Martín-MaloPedro AljamaMariano RodríguezNature PortfolioarticleKlotho ExpressionHigh Phosphate ConcentrationsOvert ProteinuriaMangiferinExcessive PhosphaturiaMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Klotho Expression High Phosphate Concentrations Overt Proteinuria Mangiferin Excessive Phosphaturia Medicine R Science Q
spellingShingle	Klotho Expression High Phosphate Concentrations Overt Proteinuria Mangiferin Excessive Phosphaturia Medicine R Science Q Rafael Santamaría Juan M. Díaz-Tocados M. Victoria Pendón-Ruiz de Mier Ana Robles M. Dolores Salmerón-Rodríguez Erena Ruiz Noemi Vergara Escolástico Aguilera-Tejero Ana Raya Rosa Ortega Arnold Felsenfeld Juan R. Muñoz-Castañeda Alejandro Martín-Malo Pedro Aljama Mariano Rodríguez Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms
description	Abstract In chronic kidney disease (CKD), high serum phosphate concentration is associated with cardiovascular disease and deterioration in renal function. In early CKD, the serum phosphate concentration is normal due to increased fractional excretion of phosphate. Our premise was that high phosphate intake even in patients with early CKD would result in an excessive load of phosphate causing tubular injury and accelerating renal function deterioration. In CKD 2–3 patients, we evaluated whether increased phosphaturia accelerates CKD progression. To have a uniform group of patients with early CKD, 95 patients with metabolic syndrome without overt proteinuria were followed for 2.7 ± 1.6 years. The median decline in eGFR was 0.50 ml/min/1.73 m2/year. Patients with a more rapid decrease in eGFR had greater phosphaturia. Moreover, the rate of decrease in eGFR inversely correlated with the degree of phosphaturia. Additionally, phosphaturia independently predicted renal function deterioration. In heminephrectomized rats, a high phosphate diet increased phosphaturia resulting in renal tubular damage associated with inflammation, oxidative stress and low klotho expression. Moreover, in rats with hyperphosphatemia and metabolic syndrome antioxidant treatment resulted in attenuation of renal lesions. In HEK-293 cells, high phosphate promoted oxidative stress while melatonin administration reduced ROS generation. Our findings suggest that phosphate loading in early CKD, results in renal damage and a more rapid decrease in renal function due to renal tubular injury.
format	article
author	Rafael Santamaría Juan M. Díaz-Tocados M. Victoria Pendón-Ruiz de Mier Ana Robles M. Dolores Salmerón-Rodríguez Erena Ruiz Noemi Vergara Escolástico Aguilera-Tejero Ana Raya Rosa Ortega Arnold Felsenfeld Juan R. Muñoz-Castañeda Alejandro Martín-Malo Pedro Aljama Mariano Rodríguez
author_facet	Rafael Santamaría Juan M. Díaz-Tocados M. Victoria Pendón-Ruiz de Mier Ana Robles M. Dolores Salmerón-Rodríguez Erena Ruiz Noemi Vergara Escolástico Aguilera-Tejero Ana Raya Rosa Ortega Arnold Felsenfeld Juan R. Muñoz-Castañeda Alejandro Martín-Malo Pedro Aljama Mariano Rodríguez
author_sort	Rafael Santamaría
title	Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms
title_short	Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms
title_full	Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms
title_fullStr	Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms
title_full_unstemmed	Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms
title_sort	increased phosphaturia accelerates the decline in renal function: a search for mechanisms
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/3a9044172f1e4892a96027f03d91d2fe
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Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms

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