Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms
| Autor: | Erena Ruiz, Juan M. Díaz-Tocados, Rosa Ortega, Alejandro Martin-Malo, Arnold J. Felsenfeld, M. Victoria Pendón-Ruiz de Mier, Escolastico Aguilera-Tejero, Pedro Aljama, M. Dolores Salmerón-Rodríguez, Mariano Rodriguez, Rafael Santamaria, Noemi Vergara, Ana I. Raya, Ana Robles, Juan R. Muñoz-Castañeda |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
030232 urology & nephrology 030204 cardiovascular system & hematology medicine.disease_cause Kidney urologic and male genital diseases Antioxidants Hyperphosphatemia 0302 clinical medicine Klotho Hypophosphatemia Familial Glucuronidase Melatonin Aged 80 and over Metabolic Syndrome Multidisciplinary Proteinuria Overt Proteinuria Middle Aged female genital diseases and pregnancy complications Medicine Female medicine.symptom Excessive Phosphaturia Hypophosphatemia Glomerular Filtration Rate Adult medicine.medical_specialty Adolescent Science Renal function Article Cell Line Phosphates 03 medical and health sciences Young Adult Internal medicine medicine Animals Humans Rats Wistar Renal Insufficiency Chronic Klotho Proteins Aged business.industry Klotho Expression Kidney metabolism medicine.disease Rats Rats Zucker Oxidative Stress Endocrinology HEK293 Cells High Phosphate Concentrations Mangiferin business Reactive Oxygen Species Oxidative stress Kidney disease |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |