Influence of dietary phosphorus in the regulation of Sodium phosphate cotransporters in uremic rats (LB717)

Abstract

Hyperphosphatemia is a common and serious complication of chronic kidney disease, contributing to the increased cardiovascular mortality seen in this patient group. The sodium phosphate (P) cotransporters system is involved in intestinal P absorption and is regulated by several factors. We investigate the effect of diets with distinct concentrations of P in the regulation of cotransporters NaPIIb and PiT1 in the intestine of rats. Male Wistar rats (n=66) were used, 33 of which were submitted to nephrectomy 5/6 (Nx) and the others were used as controls (C). The animals received a standard (ST) diet (20% protein and 0.54% P) for 30 days, after they were divided into 2 sets of 3 groups in accordance with the concentration of P in the diet (0.2%, 0.54% or 0.9%) and fed for 2 days. Blood samples, 24h urine, and intestine (duodenum, ileum and jejunum) were accordingly collected. Immunofluorescence, Western blot or ELISA were used to analyze the expressions of the cotransporters and qRT-PCR to evaluate the gene expression of NaPIIb and PiT1. The concentrations of Cr, Pi, FGF23, PTH and Albu were higher in Nx animals. Pu decreased in Nx animals and some of these parameters were modified by the concentration of dietary P. There were significant differences in the expression of PiT1 in jejunum and ileum of Nx animals in diet 0.2% P relative to their respective controls, normalized to B-actin (p=0.01 and p=0.02, respectively). The results demonstrate alteration in P homeostasis in Nx animals impaired upregulation of cotransporters in the P low diet and downregulation in the P high diet differently of the controls, as observed in PCR and immunofluorescence for PiT and NaPi in duodenum, respectively. Grant Funding Source: Supported by FAPESP