LAUSR

We read with great interest the recent paper by Martucci et al. who concluded that high-dose vitamin D3 supplementation was associated with a reduction in 28-day mortality in a mixed population of critically ill adults with vitamin D deficiency [1]. Their analysis also attempted to identify who may benefit the most from future vitamin D intervention trials [1]. We would like to make some comments. In their paper, Martucci et al. did not include data regarding patients with acute kidney injury (AKI) needing renal replacement therapy (RRT) within the critically ill population they studied [1]. 25-Hydroxyvitamin D has a molecular weight of 400 Da and thus should be easily removed by dialysis [2]. However, most of 25-hydroxyvitamin D is bound to vitamin D-binding protein, which has a molecular weight of 10 kDa and needs convection to be removed [3]. Convection, the main modality used in continuous renal replacement therapy (CRRT), can drastically reduce levels of both 25-hydroxyvitamin D and vitamin D-binding protein [3, 4]. Uhlin et al. found that the use of convection was very deleterious for 25-hydroxyvitamin D levels, with a significant reduction in 25-hydroxyvitamin D levels following the switch to online hemodiafiltration [5]. We agree with the authors that critically ill patients would benefit from vitamin D intervention trials, and given the significant loss of vitamin D in patients undergoing RRT, we believe this group of patients in particular should be a focus of further study. Studying these patients is made complicated by techniquerelated differences (type and frequency of RRT, type of membrane used, etc.) and individual patient pharmacokinetic variations (changes in volume of distribution, degree of protein binding, residual renal function, intestinal absorption of vitamin D, etc.). Perhaps the most pragmatic approach in a future study would be to give a loading dose of vitamin D, similar to that of the VITdAL-ICU study [1], and then monitor blood concentrations, like we do for antimicrobials, to guide further dosing requirements.