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Sci Rep ; 8(1): 13701, 2018 09 12.
Article in English | MEDLINE | ID: mdl-30209259

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.


Subject(s)
Hypophosphatemia, Familial/physiopathology , Kidney/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antioxidants/metabolism , Cell Line , Female , Glomerular Filtration Rate/drug effects , Glomerular Filtration Rate/physiology , Glucuronidase/metabolism , HEK293 Cells , Humans , Hyperphosphatemia/metabolism , Hyperphosphatemia/physiopathology , Hypophosphatemia, Familial/metabolism , Kidney/drug effects , Kidney/metabolism , Klotho Proteins , Male , Melatonin/pharmacology , Metabolic Syndrome/metabolism , Metabolic Syndrome/physiopathology , Middle Aged , Oxidative Stress/drug effects , Oxidative Stress/physiology , Phosphates/metabolism , Proteinuria/metabolism , Proteinuria/physiopathology , Rats , Rats, Wistar , Rats, Zucker , Reactive Oxygen Species/metabolism , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/physiopathology , Young Adult
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