POST-TRANSPLANT PHOSPHATURIA: DURATION AND PATHOGENESIS

移植后磷酸盐尿：持续时间和发病机制

• 批准号: 7606345
• 负责人: KHASHAYAR SAKHAEE
• 金额: $ 0.08万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606345
• 关键词: Acids; Computer Retrieval of Information on Scientific Projects Database; Cross-Sectional Studies; Defect; Dinoprostone; Docosahexaenoic Acids; Equilibrium; Esters; Evaluation; Fish Oils; Funding; Grant; Hypophosphatemia; Institution; Kidney; Kidney Transplantation; Longitudinal Studies; Measures; Natural History; Omega-3 Fatty Acids; Oral; Pathogenesis; Phosphorous; Phosphorus; Plasma; Prostaglandins E; Research; Research Personnel; Resources; Role; Serum; Source; Testing; Transplant Recipients; Transplantation; Tubular formation; United States National Institutes of Health; fibroblast growth factor 23; metabolic abnormality assessment; prospective; urinary; wasting

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).

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 假设：肾移植患者尽管肾移植后血清磷正常化，但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的肾小管磷重吸收缺陷中发挥致病作用，抑制PGE2的合成可以部分纠正这种缺陷。 为了检验上述假设，研究人员将通过四种方法实现以下目标： 目标 1：在移植后 12 个月至 24 个月、血清磷正常的肾移植受试者的代谢研究中确定实际磷平衡。 目标 2：通过横断面研究评估肾移植后受试者 TMPo4/GFR、FGF-23 和 PGE2 之间的相关性。 目标 3：在前瞻性纵向研究中确定移植后受试者 TMPo4/GFR 和尿 PGE2 的自然史。 目标 4：通过测量服用或口服 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）抑制 PGE2 合成前后的血浆 FGF-23 浓度、尿 PGE2 水平和 TMPo4/GFR，对移植后受试者进行干预研究 油）。