Kidney-bone, bone-kidney, and cell-cell communications in renal osteodystrophy

Abstract

The relationship between bone and the kidney in renal osteodystrophy is a complex interplay of kidney to bone connections, bone to kidney connections, and cell to cell connections. In addition, such interactions have a profound effect on the vasculature. In this review, we discuss the role of the bone morphogenetic proteins (BMPs) in the skeleton, kidney, and vasculature. In addition, we propose that deficiencies of these BMPs seen in chronic kidney disease (CKD) result in decreased bone remodeling and a compensatory secondary hyperparathyroidism (high turnover state). Treatment of the hyperparathyroidism blocks this compensatory arm and thus decreased bone remodeling occurs (low turnover). We review animal models of CKD in which treatment with BMP-7 resulted in normalization of both high and low turnover states. Finally, we discuss vascular calcification as it relates to bone metabolism. We discuss the roles of BMP-7 and 2 other bone regulatory proteins, osteoprotegerin (OPG) and alpha2-HS glycoprotein (AHSG, human fetuin), in the human vasculature and their implications for vascular calcification.