Bone In CKD Alkali Response Pilot Trial (BICARb Pilot Trial)

摘要 慢性肾脏病(CKD)是一种骨骼质量和强度受损的状态。肾 骨营养不良(Rod)是一种全球性的骨强度紊乱，存在于绝大多数CKD中 病人。患有CKD的患者的骨折发生率是没有CKD的患者的2-14倍，并且增加 与CKD的严重程度平行。儿童慢性肾脏病显著损害骨结构和 在一个对骨骼健康发展至关重要的时候，要有力量。断裂率为2-3倍 CKD儿童高于普通人群。随之而来的发病率和死亡率 与CKD中的骨折相关的研究使人们更好地了解它们的发病机制 为了开发和研究同时提高骨骼强度的治疗方法 在整个生命过程中提供可接受的安全配置文件。缺乏安全和经过验证的反病毒药物 儿童和成人CKD的骨折药物治疗策略是一个基本的 慢性肾脏病治疗中的治疗差距。 我们建议对15名儿童和88名成人进行为期6个月的随机临床试验。 第二阶段和第三阶段测试补充柠檬酸钾与服用安慰剂对骨骼强度的影响 由高分辨率外周定量计算机断层扫描(HR-pQCT)测量。我们 还将检查尿酸排泄量和骨转换的测量，以了解如何 柠檬酸钾影响骨骼健康。 这些目标将通过以下三个机构的合作努力实现：蒙特菲奥雷 蒙特菲奥雷医疗中心/儿童医院、威尔·康奈尔医学和哥伦比亚大学 大学欧文医学中心。研究团队拥有必要的专业知识和资源 进行这项临床试验。这项研究是创新的，因为柠檬酸钾从未被测试过 在一项随机、安慰剂对照的儿童和成人慢性肾脏疾病试验中。骨 儿科肾脏疾病的研究还不够深入，这项研究将是重要的第一步。 以评估柠檬酸钾作为治疗剂的作用。这项初步研究将提供重要的 未来评估柠檬酸钾对骨骼影响的更大规模U01试验的设计信息 在整个生命过程中的结果。

Abstract Chronic kidney disease (CKD) is a state of impaired bone quality and strength. Renal osteodystrophy (ROD), a global disorder of bone strength, is present in the vast majority of CKD patients. Fracture rates are 2- to 14-fold greater in patients with than without CKD and increase in parallel with CKD severity. CKD in children significantly impairs bone architecture and strength at a time that is critical for developing healthy bones. Fracture rates are 2-3 times higher in children with CKD than the general population. The attendant morbidity and mortality associated with fractures in CKD has led to efforts to better understand their pathogenesis in order to develop and study treatments that improve bone strength while simultaneously providing an acceptable safety profile across the life-course. The lack of safe and proven anti- fracture pharmacologic strategies in children and adults with CKD represents a fundamental therapeutic gap in CKD management. We propose a pilot, 6-month, randomized clinical trial in 15 children and 88 adults with CKD stages 2 and 3 to test potassium citrate supplementation vs. placebo effects on bone strength as measured by high resolution peripheral quantitative computed tomography (HR-pQCT). We will also examine urinary net acid excretion and measures of bone turnover to understand how potassium citrate effects skeletal health. These aims will be achieved through the collaborative efforts of three institutions: Montefiore Medical Center/ Children’s Hospital at Montefiore, Weill Cornell Medicine and Columbia University Irving Medical Center. The research team has the necessary expertise and resources to carry out this clinical trial. This study is innovative, as potassium citrate has never been tested in a randomized, placebo-controlled trial in chronic kidney disease in children and adults. Bone disease in pediatric kidney disease is understudied and this study will be an important first step to evaluating potassium citrate as a therapeutic agent. This pilot study will provide important information for design of a future larger U01 trial to evaluate effects of potassium citrate on bone outcomes across the life-course.