The Protein-Independent Role of Phosphate in the Progression of Chronic Kidney Disease

Toxins

Flavia Gomes Machado¹  Roberto Zatz¹  Eduardo Jorge Duque¹  Clarice Kazue Fujihara¹  Irene Faria Duayer¹  Ivone Braga de Oliveira¹  Rosa Maria Affonso Moysés¹  Luciene Machado dos Reis¹  Rosilene Motta Elias¹  Fabiana Giorgetti Graciolli¹  Vanda Jorgetti¹ 

[1] LIM 16, Nephrology Department, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, São Paulo 05403-000, Brazil;

关键词: phosphate;    diet;    CKD progression;    renal fibrosis;    autophagy;    apoptosis;   

DOI  :  10.3390/toxins13070503

来源: DOAJ

【 摘 要 】

Several factors contribute to renal-function decline in CKD patients, and the role of phosphate content in the diet is still a matter of debate. This study aims to analyze the mechanism by which phosphate, independent of protein, is associated with the progression of CKD. Adult Munich-Wistar rats were submitted to 5/6 nephrectomy (Nx), fed with a low-protein diet, and divided into two groups. Only phosphate content (low phosphate, LoP, 0.2%; high phosphate, HiP, 0.95%) differentiated diets. After sixty days, biochemical parameters and kidney histology were analyzed. The HiP group presented worse renal function, with higher levels of PTH, FGF-23, and fractional excretion of phosphate. In the histological analysis of the kidney tissue, they also showed a higher percentage of interstitial fibrosis, expression of α-actin, PCNA, and renal infiltration by macrophages. The LoP group presented higher expression of beclin-1 in renal tubule cells, a marker of autophagic flux, when compared to the HiP group. Our findings highlight the action of phosphate in the induction of kidney interstitial inflammation and fibrosis, contributing to the progression of renal disease. A possible effect of phosphate on the dysregulation of the renal cell autophagy mechanism needs further investigation with clinical studies.

【 授权许可】

Unknown