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

Abstract

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.

Heidihuangwan alleviates renal fibrosis in rats with 5/6 nephrectomy by inhibiting autophagy

“…In adult Sprague Dawley rats, the expression of autophagy marker proteins Beclin1, LC3II, PRR, ATG7, and ATG5 was significantly lower in glomeruli than in normal rats 8 weeks after undergoing 5/6 nephrectomy (Yildirim et al, 2021). In addition, a high phosphorus diet increased renal impairment and interstitial fibrosis in 5/ 6 nephrectomized Wistar rats, a process that was shown to be associated with inhibition of autophagy (Duayer et al, 2021). On the other hand, there is also evidence to support that autophagy activation promotes renal fibrosis.…”

Parathyroid hormone receptor-1 signaling aggravates hepatic fibrosis through upregulating cAMP response element-binding protein-like 2

“…[20] In the kidney tissue, higher levels of PTH due to phosphate accumulation or vitamin D deficiency show increased interstitial fibrosis. [21][22][23] In addition, PTH is a significant predictor of bone mineral density and linked to cystic fibrosis [24] and arteriosclerotic fibrosis. [25,26] Conditional deletion of PTH1R increased collagen gene expression and aortic fibrosis in the vascular smooth muscle lineage.…”

Effects of a nutrition education program on self-care behavior and kidney functions in pre-dialysis chronic kidney disease patients

“…These findings were speculated to be due to effective dietary counseling. Salt limitation is a well-known method to reduce the blood sodium level, while the restriction of certain types of fruits and vegetables were beneficial to lower potassium and phosphorus levels (Duayer et al, 2021;Nagasawa, 2021;Yamada & Inaba, 2021). Larger scale study in this group of patients is needed to unravel mechanistic details the program.…”