POST-TRANSPLANT PHOSPHATURIA: DURATION AND PATHOGENESIS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 假设：尽管肾移植后血磷恢复正常，但肾移植患者仍存在肾磷消耗和负磷平衡。 成纤维细胞生长因子-23（FGF-23）和/或前列腺素E-2（PGE-2）在肾移植后低磷血症肾小管磷重吸收缺陷中起重要作用，抑制PGE-2的合成可部分纠正这一缺陷。 为了检验上述假设，研究者将通过四种方法实现以下目标： 目标1：在肾移植后受试者的代谢研究中确定实际磷平衡，移植后12个月至24个月，血清磷正常。 目的2：在横断面研究中评估肾移植后受试者的TMPo 4/GFR、FGF-23和PGE 2之间的相关性。 目的3：在一项前瞻性纵向研究中确定移植后受试者的TMPo 4/GFR和尿PGE 2的自然史。 目标4：在移植后受试者中进行一项干预性研究，通过测量口服omega-3多不饱和脂肪酸乙酯[二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）]（鱼油）抑制PGE 2合成前后的血浆FGF-23浓度、尿PGE 2水平和TMPo 4/GFR。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: Renal transplant patients continue to have renal phosphorus wasting and negative phosphorus balance despite the normalization of serum phosphorus after renal transplantation. Fibroblast Growth Factor-23 (FGF-23) and or prostaglandin E-2 (PGE-2play a pathogenetic role in defective renal tubular phosphorus reabsorption in post-renal transplant hypophosphatemia and inhibition of synthesis of PGE2 can partially correct this defect. To test the above hypothesis, the investigators will achieve the following objectives with four approaches: Aim 1: To determine actual phosphorous balance in a metabolic study in post-renal transplantation subjects, 12 months to 24 months post-transplantation, with normal serum phosphorous. Aim 2: To evaluation post-renal transplantation subjects in a cross sectional study for a correlation between TMPo4/GFR, FGF-23, and PGE2. Aim 3: To determine in a prospective longitudinal study the natural history of TMPo4/GFR, and urinary PGE2 in post-transplantation subjects. Aim 4: To conduct an interventional study in post-transplantation subjects by measuring plasma FGF-23 concentration, urinary PGE2 levels, and TMPo4/GFR before and after inhibition of PGE2 systhesis by administration or oral omega-3 polyunsaturated fatty acid ethyl esters [Eicosapentaonoic acid (EPA) and Docosahexaenoic acid (DHA)](Fish Oil).