Bone Abstracts

Chronic kidney disease (CKD) is defined according to the presence of kidney damage and level of kidney function – irrespective of the type of kidney disease (diagnosis). Among individuals with chronic kidney disease, the stages are defined based on the level of glomerular filtration rate. From infancy through young adulthood, the major causes of CKD arise from congenital abnormalities of the kidneys and urinary tract (CAKUT), acquired or congenital forms of nephrotic syndrome, genetic forms of renal tubular dysfunction, and a host of other diseases affecting the glomerulus and/or the tubule-interstiitum of the kidney, often with a genetic component. Changes in normal bone function occur early in the course of CKD and worsen as CKD progresses into the need for renal replacement therapies of dialysis or kidney transplantation. The entity of bone disease associated with CKD is not termed CKD-Mineral Bone Disturbance (CKD-MBD). The clinical manifestations of CKD-MBD in bone include frank rickets, deformities, fractures, and linear growth failure. The mechanisms for these manifestations relate to the biochemical findings of CKD, including metabolic acidosis, changes in blood calcium and phosphorus, and multiple hormonal disturbances, including those in parathyroid hormone, fibroblast growth factor 23, sclerostin and wnt-signalling, among others. As important as the changes in bone cell function are, is the understanding that the disturbance in mineralization in bone is transferred to the cardiovascular system, leading to pathologic vascular calcifications throughout the body. Recent and novel mechanisms for this will be discussed, and the relevance to other bone diseases in which vascular calcification occur will be elucidated. Treatment of CKD-MBD is fraught with absence of evidence for optimal protocols, no clinical trials in childhood, and few approved therapeutic agents. Thus, the clinician is often faced with uncertain nodal choices for each and every patient, leading to uncertain outcomes and ways to document success. Trial networks must be established to best understand meaningful outcomes, especially in the cardiovascular system.

Disclosure: Honoraria for self-created lectures, Alexion. University receives funding for registries. Alexion Consultant. Dicerna.