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

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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.