Control of phosphate appetite in young rats

In the present study, we investigated whether a diet deficient in inorganic phosphate (Pi) stimulates an ingestive behavior to seek sources of Pi. Male Wistar rats were placed in individual cages with unrestricted access to tap water and a low (LPD, 0.02% Pi) or normal (NPD, 0.6% Pi) Pi diet for 6 days. On day 7, LDP rats were given unlimited access to a solution of 25 mM potassium phosphate water (Pi-water) for 9 additional days. Rats fed LPD consumed 70-100% more Pi-water then those fed NPD. The increase in Pi-water intake resulted in a marked rise in the growth rate of rats fed LPD during day 9. A similar intake of Pi was induced after only 2 days of LPD and was associated with significant reductions in both plasma and cerebrospinal fluid (CSF) levels of Pi ; these levels remained low throughout Pi restriction, despite a significant intake of Pi-water. Replenishment with a high-Pi diet rapidly quenched the appetite for Pi-water and was associated with restoration of both plasma and CSF Pi levels. These findings suggest that an appetite for Pi can be induced in rats, perhaps through lowered plasma and CSF Pi levels

Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium

Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axis serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. Following Cd injection into WT mice, plasma FGF23 concentration was significantly increased. Urinary Pi excretion levels were significantly higher in Cd-injected WT mice than in control group. Plasma Pi concentration decreased only slightly compared with control group. No change was observed in plasma parathyroid hormone and 1,25-dihydroxy vitamin D3 in both group of mice. We observed a decrease in phosphate transport activity and also decrease in expression of renal phosphate transporter SLC34A3 [NaPi-IIc/NPT2c], but not SLC34A1 [NaPi-IIa/NPT2a]. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice which expresses Npt2c as a major NaPi co-transporter. Injecting Cd to Npt2aKO mice induced significant increase in plasma FGF23 concentration and urinary Pi excretion levels. Furthermore, we observed a decrease in phosphate transport activity and renal Npt2c expression in Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with the FGF23/klotho axis

Dietary inorganic phosphorus and intestinal peptide absorption

Both organic and inorganic phosphorus (Pi) are present in regularly consumed foods such as meats, eggs, and dairy products. Pi is often included in foods as an additive, as hidden phosphorus. The intestinal peptide transporter PepT1 mediates protein absorption, which is disturbed in renal insufficiency. In the present study, we examined the effects of dietary Pi content on the intestinal peptide transport activity and expression of PepT1. The following animal models were used: 1) 7-week-old, male Wistar rats; and 2) rats that underwent 3/4 nephrectomy (3/4NR) to induce chronic kidney disease (CKD). Rats were fed a normal-protein (20%) diet containing low (0.02%), normal (0.6%) or high (1.2%) Pi levels. Rats were also fed diets containing varying amounts of protein and either low or normal Pi levels, as follows: 1) low Pi/normal protein, 2) low Pi/high (50%) protein, 3) normal Pi/normal protein, and 4) normal Pi/high protein. Intestinal peptide transport activity and PepT1 expression levels were significantly higher in CKD rats than in sham-operated controls. Compared with the normal diet, the high-protein diet increased PepT1 expression in CKD rats. Intestinal di-peptide transport activity and PepT1 protein levels did not increase in rats fed the low-Pi/high-protein diet. In contrast, intestinal di-peptide transport activity and PepT1 protein expression were markedly increased in rats fed the normal-Pi/high-protein diet.In conclusion, dietary Pi levels regulate intestinal peptide transport activity via PepT1

Risk Reduction for End-Stage Renal Disease by Dietary Guidance Using the Gustatory Threshold Test for Salty Taste

Educational hospitalization of patients with chronic kidney disease (CKD) may slow the progression of renal dysfunction. However, the educational aspect that is more effective has not been identified to date. In this study, patients with CKD were evaluated for gustatory threshold for salty taste and received augmented salt reduction guidance under educational hospitalization at Nagasaki University Hospital from October 2016. In total, 277 eligible patients were enrolled and hospitalized from 2012 to 2019 (mean age of 69.2 years; men comprised 62.1%). We compared 141 patients (Group A) who were educated in the hospital after October 2016 and 136 patients (Group B) who received standard education in the hospital before October 2016. The changes in the estimated glomerular filtration rate (ΔeGFR) after hospitalization and dialysis induction rate within one year after hospitalization were evaluated. The ΔeGFR was significantly improved in Group A compared to Group B (A: 1.05 mL/min/1.73 m2/month, B: 0.55 mL/min/1.73 m2/month; p = 0.02). The dialysis induction rate was significantly lower in Group A than in Group B (A: 8.5%, B: 15.5%; p = 0.001). These trends were also observed by multivariate analyses. In conclusion, educational hospitalization with enhanced salt reduction guidance may reduce the risk of end-stage renal disease

Type IIc Sodium–Dependent Phosphate Transporter Regulates Calcium Metabolism

Primary renal inorganic phosphate (Pi) wasting leads to hypophosphatemia, which is associated with skeletal mineralization defects. In humans, mutations in the gene encoding the type IIc sodium–dependent phosphate transporter lead to hereditary hypophophatemic rickets with hypercalciuria, but whether Pi wasting directly causes the bone disorder is unknown. Here, we generated Npt2c-null mice to define the contribution of Npt2c to Pi homeostasis and to bone abnormalities. Homozygous mutants (Npt2c−/−) exhibited hypercalcemia, hypercalciuria, and elevated plasma 1,25-dihydroxyvitamin D3 levels, but they did not develop hypophosphatemia, hyperphosphaturia, renal calcification, rickets, or osteomalacia. The increased levels of 1,25-dihydroxyvitamin D3 in Npt2c−/− mice compared with age-matched Npt2c+/+ mice may be the result of reduced catabolism, because we observed significantly reduced expression of renal 25-hydroxyvitamin D–24-hydroxylase mRNA but no change in 1α-hydroxylase mRNA levels. Enhanced intestinal absorption of calcium (Ca) contributed to the hypercalcemia and increased urinary Ca excretion. Furthermore, plasma levels of the phosphaturic protein fibroblast growth factor 23 were significantly decreased in Npt2c−/− mice. Sodium-dependent Pi co-transport at the renal brush border membrane, however, was not different among Npt2c+/+, Npt2c+/−, and Npt2c−/− mice. In summary, these data suggest that Npt2c maintains normal Ca metabolism, in part by modulating the vitamin D/fibroblast growth factor 23 axis