Intestinal and Renal Pi Transport Adaptation and Hormonal Changes in Response to Acute Changes in Dietary Pi

Abstract

A hallmark of the successful control of Pi homeostasis is the adaptation of Pi intestinal absorption and renal excretion to changes in the dietary content of Pi. Acute and chronic adaptation mechanisms have been described for both tissues, yet despite these efforts, many questions related to hormonal changes and transport systems are still unclear. Male Wistar rats were fed well-balanced fodder containing either 0.1, 0.6, or 1.2% Pi, prepared with NaH2PO4 and K2HPO4 to pH 7.4 and compensated with NaCl and KCl. Some rats were fed ad libitum for 6 days, while other animals were fed only 4 hours in the morning for 6 days. Some of the rats from this 4-hour feeding scheme that had been fed either 0.1 or 1.2% Pi fodder for 5 days received the opposite fodder on the 6th day. Food consumption, Pi ingestion, and growth were determined. Pi deficiency-related acidosis was minimally observed in the animals that, after 5 days eating 1.2% Pi food, were switched to 0.1% Pi on the 6thday: blood pH was reduced to 7.32, bicarbonate fell to 25.2 mM, and the base excess dropped to -1.74 mM. Pi transport in jejunum and kidney cortex brush border membrane vesicles (BBMV) was always higher in the animals chronically fed with 0.1% Pi, and it was similar at 0.6 and 1.2% Pi. In the case of animals whose diet was switched the last day, there were no differences in jejunum BBMV Pi transport, in contrast to previous studies that have shown a higher transport rate after switching to a high Pi content. In kidney BBMV, Pi transport was higher in the change from 1.2 to 0.1% Pi. Plasma Pi was always proportional to the fodder Pi content. Plasma FGF23 and PTH concentrations varied similarly and were always proportional to the ingested Pi in all groups, including the animals whose food was switched, meaning that both hormones changed after 4 hours of high Pi intake. Differences in the phosphatonins sFR4 and MEPE were not significant. Also, no differences were observed in dopamine, corticosterone, insulin, thyroxine, calcitriol, or Klotho. A similar experiment was performed in parathyroidectomized (PTX) rats, but only using the 4-hour feeding regime. Food consumption and growth was similar in sham and PTX animals. Blood plasma Pi was higher in PTX animals in all groups except for those chronically fed at 0.1% Pi. Transport in jejunum BBMV was similar in sham and PTX rats, and NaPi2b protein abundance correlated with the transport rate. In kidney BBMV, all groups showed higher transport rates in PTX rats (except for the chronic 0.1% Pi group, in which the rates were similar), and no differences were observed between the animals whose food was acutely switched the last day, therefore confirming the role of PTH over the relevance of FGF23 in the kidney's acute response. All hormones behaved similarly in sham and PTX animals, except for dopamine, which was very low in the 0.1%-Pi fed PTX rats, and FGF23 which was surprisingly lower in all groups compared to sham rats. In conclusion, a pH- and ion-balanced fodder prevented the paradoxical increase of Pi intestinal uptake when a Pi-enriched food was given. This food also prevented the strong metabolic acidosis associated with experimentally Pi-depleted fodder. Acute adaptation only occurs in the kidney, and PTH is the hormone that mediates it.