Survival benefits with vitamin D receptor activation: new insights since 2003

The introduction of calcitriol followed by several of its analogs in the 1990s made vitamin D receptor activators (VDRA) the cornerstone of therapy for secondary hyperparathyroidism. The 2003 publication of the first major epidemiologic study describing the association of VDRAs with survival in ESRD has raised the awareness of the nephrology community about the potential impact of these agents on morbidity and mortality. This study was followed by numerous other epidemiologic studies which attempted to address the inherent shortcomings of observational studies by using sophisticated statistical methods. The complex nature of the statistical designs applied by some of these studies has led to some confusion about how to interpret the results, and how to use the results in a way that offers the most help for patients, but does not impede future scientific research. This report presents a discussion of relevant studies examining the association between VDRA and survival, with the goal to examine shortcomings that still exist in the knowledge on this subject. Special emphasis is placed on the discussion of studies with discrepant results to highlight remaining controversies and to emphasize areas in need of further research. Not withstanding all of the limitations of epidemiologic studies, the preponderance of evidence favors a survival benefit for ESRD patients treated with VDRA. This should provide a powerful impetus to investigate in clinical trials the risks and benefits of VDRA administration as a means to prolong survival.