Chronic Renal Insufficiency in NAPRTCS Patients

描述（由申请人提供）： 该申请是NAPRTCS 26个中心的共同努力，标题为“NAPRTCS患者的慢性肾功能不全（CRI）”。我们将招募300名儿童（1-16岁），测量的肾小球滤过率（GFR）为25-75 mL/min/1.73 m2。随访年度GFR和6个月体格检查以及血红蛋白、电解质、血清、白蛋白、血清钙、血清磷、甲状旁腺激素和尿指标的测定将检验第一个假设，即该队列将最准确地定义CRI进展的速率和风险因素，并且该进展将与蛋白尿、白蛋白、血压、营养状态、生长和甲状旁腺功能亢进。为了检验第二个假设，即轻度CRI儿童发生心血管疾病，其患病率和严重程度随着CRI的进展而增加，我们将进行基线和每年24小时动态血压监测，超声心动图评估以确定左心室质量和LV功能，以及颈动脉B型超声以确定IMT和颈动脉顺应性。为了检验第3个假设，即CRI儿童的神经认知结局受肾功能不全进展的影响，将在研究入组时以及6、12和24个月时进行一系列经验证的神经认知测试，以评估大脑功能的许多皮质和皮质下区域。为了检验慢性炎症导致恶病质、生长激素抵抗和生长迟缓的第4个假设，我们将检查循环细胞因子和神经肽浓度对饮食摄入、营养和生长参数以及生长激素轴扰动和对生长激素治疗的反应性的影响。最后，为了检验骨组织学、PTH血清浓度和GFR测定值之间存在相关性的第5个假设，我们将测量和表征肾性骨营养不良的生化和组织学特征，并确定与正常骨形成率相关的PTH血清浓度。

DESCRIPTION (provided by applicant): This application, a joint effort of 26 centers of the NAPRTCS, is entitled "Chronic Renal Insufficiency (CRI) in NAPRTCS Patients. We will enroll 300 children (1-16 years) with measured glomerular filtration rates (GFR) of 25-75 mL/min/1.73m2. Follow-up with annual GFR and 6 month physical examinations and determinations of hemoglobin, electrolytes, serum, albumin, serum calcium, serum phosphorus, parathyroid hormone and urinary indices will test the 1st hypothesis that this cohort will most accurately define the rate of and the risk factors for progression of CRI, and that this progression will be correlated with proteinuria, albumin, blood pressure, nutritional status, growth and hyperparathyroidism. To test the 2nd hypothesis that cardiovascular disease develops in children with mild CRI and that its prevalence and severity increase in association with the progression of CRI, we will perform baseline and annual 24-hour ambulatory blood pressure monitoring, echocardiographic assessments to determine left-ventricular mass and LV function, and B-mode ultrasound of the carotid artery to determine the IMT and carotid artery compliance. To test the 3rd hypothesis that the neurocognitive outcome of children with CRI is influenced by the progression of renal insufficiency, a battery of validated neurocognitive tests will be conducted at study entry and at 6, 12 and 24 months to assess many cortical and subcortical areas of brain function. To test the 4th hypothesis that chronic inflammation contributes to cachexia, growth hormone resistance and growth retardation, we will examine the impact of circulating cytokine and neuropeptide concentrations on dietary intake, nutritional and growth parameters as well as growth hormone axis pertubations and responsiveness to growth hormone therapy. Finally, to test the 5th hypothesis that a correlation exist between bone histology, serum concentration of PTH and measured GFR, we will measure and characterize the biochemical and histologic features of renal osteodystrophy and determine the serum concentrations of PTH that are associated with normal rates of bone formation.