ARRA: Renal Osteodystrophy: A Fresh Approach

This is a supplemental application to a recently funded R01- 0DK080770 “Renal Osteodystrophy: A Fresh Approach.” Patients with chronic kidney disease (CKD) present with a specific mineral and bone disorder (CKD-MBD) which is associated with high morbidity and mortality. Renal osteodystrophy (ROD) is the bone histologic abnormality of CKD-MBD. One of the most relevant bone abnormalities of ROD is low bone mass and bone loss. Preliminary studies show that low bone mass or bone loss may be associated with progressive vascular calcifications explaining the high morbidity and mortality. The original R01 pursues the central hypothesis that ROD can be defined non-invasively. For this purpose a large number of CKD-5 patients with ROD are recruited and bone mass and bone loss are determined annually by quantitative computed tomography (QCT) and dual energy X-ray absorptiometry (DXA). This pool of patients is available for measurements of coronary artery calcifications (CAC) when they present for their QCT and DXA measurements as part of the ongoing funded study. Adding CAC measurements by multi-slice computed tomography (MSCT) provides an opportunity to evaluate the intriguing hypothesis that bone volume (in the cross-sectional study) and bone loss (in the prospective study) are associated with extent and progression of CAC. The number of available patients allows evaluation of traditional and non-traditional risk factors that may confound observed effects. This is a great opportunity to maximize information from already committed NIH funds. The long-term goal of the proposed supplemental study is to improve survival and quality of life in CKD patients by demonstrating the association between bone loss and CAC. In these patients, cardiovascular disease is the leading cause of their high morbidity and mortality. The following specific aims will be pursued in CKD patients on dialysis: 1. To demonstrate a significant association between CAC and low bone mass. This will be accomplished by adding measurements of CAC and blood tests for determination of traditional and non-traditional risk factors for CAC to the ongoing studies employing DXA and QCT of the spine and hip. 2. To establish bone loss as a risk factor for progression of CAC. This will be accomplished by adding measurements of CAC and blood tests for determination of traditional and non-traditional risk factors for CAC to the ongoing study employing DXA and QCT of the spine and hip at baseline and one year thereafter. Establishment of bone mass and/or bone loss as predictor(s) of CAC in this large patient population would justify further research into mechanisms and development of specific therapeutic measures which could result in dramatic reduction of disease burden and health care costs.