Mortality reduction by vitamin D receptor activation in end-stage renal disease: a commentary on the robustness of current data

Background. Debate exists about assumed mortality effects of the use of vitamin D receptor activators (VDRA) in haemodialysis patients. Methods. In the absence of randomized controlled trials (RCTs), current knowledge comes from several large observational studies that examined the association between the use of VDRA and mortality. In these trials, modern but complicated statistical analysis has been performed, attempting to minimize potential bias of suboptimal study design. This complexity may lead to suspicion about study results, and for this reason these results may be discarded for everyday clinical practice. Results. In the current commentary, several crucial aspects of applied statistics are highlighted, attempting to aid practicing clinicians to properly weigh these study results in a balanced way. The difference between historical and retrospective cohort analysis is addressed, as well as the use of sensitivity analysis and propensity scores. The impact of confounding, mediation and effect modification for these studies on VDRA use is discussed. Conclusions. It is concluded that the results from these studies appear quite robust and consistent. Furthermore, there is an increasing amount of data from experimental data suggesting mechanisms for observed beneficial effects. However, it must be kept in mind that VDRA can have adverse effects and that observational data can never replace RCTs.