Abstract
Vitamin D receptor activators (VDRA) may exert pleiotropic effects on cardiovascular disease, malignancy, and infections among dialysis patients, but recent studies have mainly focused on cardiovascular outcomes. Among 8,675 patients who started dialysis in 2007 and who survived until January 1, 2010, listed in the Renal Data Registry of the Japanese Society for Dialysis Therapy, 5,365 VDRA users were matched to 3,203 non-users based on clinically relevant variables at the end of 2009 using the coarsened exact matching procedure. Until December 31, 2011, a total of 1,128 deaths occurred, of which 468 (42%) were cardiovascular deaths, 229 (20%) were infection-related deaths, and 141 (12%) were malignancy-related deaths. Multivariable survival analyses accounting for intra-region correlation revealed that VDRA use was significantly associated with lower rates of infection- and malignancy-related deaths [subhazard ratio 0.62 (95% CI, 0.52–0.73) and 0.70 (95% CI, 0.50–0.97), respectively] but not with cardiovascular death [subhazard ratio 0.86 (95% CI, 0.72–1.04)]. Future randomized clinical trials with a sufficient sample size and an adequate follow-up period are warranted to test the clinical effectiveness of VDRA on infection and malignancy, rather than cardiovascular disease, among dialysis patients.
Highlights
Vitamin D may exert protective effects against cardiovascular disease, infection, and malignancy[1], which are among the most frequent causes of death in patients with end-stage renal disease (ESRD)[2,3]
Among 8,675 ESRD patients who started dialysis in 2007 and who survived until January 1st, 2010, a total of 5,365 Vitamin D receptor activators (VDRA) users as of December 2009 were matched to 3,203 non-users based on age, sex, diabetes, history of CVD, initial dialysis modality (HD or PD), and estimated glomerular filtration rate (GFR) at dialysis initiation using the coarsened exact matching procedure (Fig. 1)[14]
Given the low prevalence of VDRA use during the pre-dialysis period in Japan (i.e.
Summary
Vitamin D may exert protective effects against cardiovascular disease, infection, and malignancy[1], which are among the most frequent causes of death in patients with end-stage renal disease (ESRD)[2,3]. Given the high prevalence of vitamin D deficiency and the diminished activity of renal 1α-hydroxylase in ESRD patients, treatment with vitamin D receptor activators (VDRAs) may offer a survival benefit, in addition to their effects on mineral and bone metabolism, by reducing the risk of these disease conditions[4]. Some studies support the survival benefit of VDRA use in patients with chronic kidney disease (CKD), including ESRD5–8, while another study found no association with mortality using an instrumental variable approach that may reduce the influence of unmeasured confounders[9]. VDRA, which downregulates renin expression, may not be effective in preventing cardiovascular disease because in the current clinical practice, many patients with CKD receive renin-angiotensin system inhibitors[10,11]. We used a nationwide cohort of Japanese dialysis patients to test our hypothesis that VDRA use is more strongly associated with infection- or malignancy-related death compared to cardiovascular death
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