RT Journal Article
T1 Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms.
A1 Santamaria, Rafael
A1 Diaz-Tocados, Juan M
A1 Pendon-Ruiz de Mier, M Victoria
A1 Robles, Ana
A1 Salmeron-Rodriguez, M Dolores
A1 Ruiz, Erena
A1 Vergara, Noemi
A1 Aguilera-Tejero, Escolastico
A1 Raya, Ana
A1 Ortega, Rosa
A1 Felsenfeld, Arnold
A1 Muñoz-Castañeda, Juan R
A1 Marin-Malo, Alejandro
A1 Aljama, Pedro
A1 Rodriguez, Mariano
K1 Proteinuria
K1 Rats, Zucker
K1 Reactive Oxygen Species
K1 Renal Insufficiency, Chronic
K1 Young Adult
AB 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.
PB Nature Publishing Group
YR 2018
FD 2018-08-20
LK http://hdl.handle.net/10668/12939
UL http://hdl.handle.net/10668/12939
LA en
NO Santamaría R, Díaz-Tocados JM, Pendón-Ruiz de Mier MV, Robles A, Salmerón-Rodríguez MD, Ruiz E, et al. Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms. Sci Rep. 2018 Sep 12;8(1):13701
NO Tis work has been partially supported by a Spanish Government Grant from the Programa Nacional I+D+I 2008–2011 from the Instituto de Salud Carlos III (PI14/00638 and PI14/00467) with co-fnancing from European Funds (FEDER), Consejería de Economía, Innovación, Ciencia y Empleo from the Junta de Andalucía (CVI7925) and REDINREN from Instituto de Salud Carlos III (ISCIII) and EUTOX. Tis work was also supported by PI-0311-2014 Junta de Andalucía and PI12/01866 and EUTOX. JR Muñoz-Castañeda is a senior researcher supported by the Nicolás Monardes Programme, Consejeria de Salud-SAS (Junta de Andalucía).
DS RISalud
RD Apr 6, 2025