Pathogenesis of Compromised Bone Quality and Mechanics in Chronic Kidney Disease

Overview

Kidney disease patients have a variety of bone disorders that result in bone loss and fractures. The mechanisms of these bone disorders are not clear but may be related to abnormal modification of a bone protein known as collagen. Therefore, the investigators are conducting this research study to identify underlying mechanisms that are responsible for the disruption of bone collagen and determining whether the abnormal bone collagen impairs bone strength. The investigators intend to identify these mechanisms through studying relationships between kidney disease and bone strength via bone imaging, bone biopsy and non-invasive measures from blood and skin.

Kidney disease patients have abnormal protein (bone collagen) modifications in their bone that may increase the risk of breaking a bone (fracture). Preventing bone collagen from becoming abnormal may decrease the risk of breaking a bone, such as the spine or hip. Currently, the effect of abnormal bone collagen on bone strength is not fully defined, and there are no methods to measure the abnormal protein content without a bone biopsy. The purpose of this study is to define the effects of bone collagen on bone strength and to identify non-invasive markers that will tell us how much abnormal collagen is in the bone. If the investigators are able to identify a non-invasive marker of abnormal bone protein then they may be able to prevent the build-up of this protein and lower the risk of a fracture. If the participant chooses to be in the study, the investigators will get information from the participant's medical records such as diagnosis, the medicines and treatments prescribed by the participant's doctor, and the participant's lab test results. There will be two study visits, each lasting about 3 hours. Visit 1: At the baseline visit, study procedures include: * Completing medical history, physical activity level, and dietary questionnaires for calcium and vitamin D. * Blood sample * Bone Imaging will: dual energy X-ray absorptiometry (DXA) to measure bone mineral density, high-resolution peripheral quantitative computed tomography (HRpQCT) to measure bone quality, and back x-rays to assess for the presence of spine fractures.Females who are able to become pregnant will also provide a urine specimen for pregnancy testing. (A negative pregnancy test is required prior to bone imaging.) * Measure levels of Advanced Glycation End products (AGEs) in the skin of the participant's forearm and also in the participant's bone by bone biopsy. Advance Glycation End products may play a role in the development of weakened bone due to chronic kidney disease. Visit 2: The participant's second visit will occur within 6-months of enrollment. At this visit, the participant will undergo a bone and muscle biopsy at the hip area under conscious sedation and a localized pain numbing medicine. The bone biopsy provides detailed information about the quality of the participant's bone that cannot be obtained through other tests like x-rays or blood tests. The investigators will use the bone biopsy to determine the amount of abnormal protein in the participant's bone. The muscle biopsy informs about the health of the participant's muscle fibers and allows us to detect any muscle mass wasting associated to chronic kidney disease. Since the piece of muscle is taken form the bone biopsy, no extra incision is needed. The duration of the participant's participation from start of antibiotics through the actual bone biopsy will be approximately 3 weeks and 5 days (26 days).