Oral active vitamin d therapy as a potential chemoprevention against post-transplant malignancy

Abstract

Post-transplant malignancy (PTM) is a limiting factor for both patient and allograft survival in kidney transplant recipients (KTRs). We hypothesized that active vitamin D compounds (AVDs) could reduce the development of PTM in KTRs and evaluated the effects of AVD therapy in a prospective cohort of ambulatory KTRs in a Japanese single center. We used a propensity score (PS) of having received AVDs estimated by 25 clinically relevant factors to adjust for these confounders. Among 218 participants, the mean age was 49.4 (SD, 12.1) years, 63.3% were male, the median time since transplantation was 11.2 (interquartile range [IQR], 5.2–17.1) years, and 42.2% had been treated with AVDs at baseline. The AVDs consisted of calcitriol (58.7%) and alfacalcidol (41.3%), and their median doses were 0.5 (IQR, 0.5–0.5) μg and 0.5 (IQR, 0.25–1.0) μg, respectively. During a median follow-up of 2.9 (IQR, 2.1–3.0) years, PTM was observed to have developed in 5 (5.4%) of 92 AVD users and in 11 (8.7%) of 126 non-users. Cox regression analysis with stratification by the PS tertiles showed that AVDs were significantly associated with a lower risk of PTM (hazard ratio, 0.25 [95% confidence interval, 0.07–0.82], P=0.022). The level of serum 25-hydroxyvitamin D was generally low (median, 16.6 ng/ml), and not significantly associated with PTM. Sensitivity analyses with stratification by PS quartiles, PS matching, or inverse probability weighting yielded similar results. Our results suggest a novel potential strategy to prevent PTM by using a normal dose of AVDs with a well-known safety profile. A randomized controlled trial should be performed to confirm our findings.