Kidney Res Clin Pract.
2012 Mar;31(1):12-25.
Cardiorenal syndrome and vitamin D receptor activation in chronic kidney disease
- Affiliations
-
- 1Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. kamkal@ucla.edu
- 2St. John Cardiovascular Reserach Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
- 3David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
- 4Salem Veterans Affairs Medical Center, Salem, VA, USA.
- 5UCLA School of Public Health, Los Angeles, CA, USA.
Abstract
- Cardiorenal syndrome (CRS) refers to a constellation of conditions whereby heart and kidney diseases are pathophysiologically connected. For clinical purposes, it would be more appropriate to emphasize the pathophysiological pathways to classify CRS into: (1) hemodynamic, (2) atherosclerotic, (3) uremic, (4) neurohumoral, (5) anemic??hematologic, (6) inflammatory-oxidative, (7) vitamin D receptor (VDR) and/or FGF23-, and (8) multifactorial CRS. In recent years, there have been a preponderance data indicating that vitamin D and VDR play an important role in the combination of renal and cardiac diseases. This review focuses on some important findings about VDR activation and its role in CRS, which exists frequently in chronic kidney disease patients and is a main cause of morbidity and mortality. Pathophysiological pathways related to suboptimal or defective VDR activation may play a role in causing or aggravating CRS. VDR activation using newer agents including vitamin D mimetics (such as paricalcitol and maxacalcitol) are promising agents, which may be related to their selectivity in activating VDR by means of attracting different post-D-complex cofactors. Some, but not all, studies have confirmed the survival advantages of D-mimetics as compared to non-selective VDR activators. Higher doses of D-mimetic per unit of parathyroid hormone (paricalcitol to parathyroid hormone ratio) is associated with greater survival, and the survival advantages of African American dialysis patients could be explained by higher doses of paricalcitol (>10 microg/week). More studies are needed to verify these data and to explore additional avenues for CRS management via modulating VDR pathway.
