DEVELOPMENT OF RENAL PHOSPHATE REGULATION

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The need for young, immature animals to maintain positive phosphate balance for growth is well recognized. However, the adaptations that occur in the kidney to facilitate this process have not been clarified. The objective is to evaluate the intrarenal regulation of phosphate reabsorption during development. Micropuncture techniques will be used to examine the nephron sites of phosphate reabsorption and their response to dietary and hormonal factors regulating phosphate homeostasis. Comparisons will be made between immature, weaned rats (3-4 weeks) and adult rats (6 months). The hypothesis to be tested is that the developing animal displays avid phosphate reabsorption due to greater participation of deep nephrons and enhanced reabsorption in distal nephron segments. Furthermore, relative hyporesponsiveness to phosphaturic stimuli also contributes to the renal retention of phosphate. Specific protocols are designed to evaluate the following parameters: a) the nephron sites of phosphate reabsorption, b) the transport capacities of superficial and deep nephron proximal tubules, c) the response of these sites to phosphaturic stimuli (high phosphate diet, PTH, calcitonin), and d) the possible restoration of responsiveness to hhosphaturic hormones (with acute phosphate infusions, diphosphonate treatment). These studies will provide important information regarding the intrarenal mechanisms involved in the adaptations for growth.