Orally Active Vitamin D for Potential Chemoprevention of Post-transplant Malignancy
Yoshitsugu Obi1, Naotsugu Ichimaru2, Takayuki Hamano3,*, Kodo Tomida4, Isao Matsui1, Naohiko Fujii5, Masayoshi Okumi6, Jun-ya Kaimori7, Koji Yazawa6, Yukito Kokado8, Yoshiharu Tsubakihara9, Norio Nonomura10, Hiromi Rakugi11, Shiro Takahara12, and Yoshitaka Isaka11
1 Department of Geriatric Medicine & Nephrology, Osaka University Graduate School of Medicine
2 Department of Urology, Osaka Central Hospital
3 Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine
4 Department of Kidney Disease and Hypertension, Osaka General Hospital
5 Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital
6 Department of Specific Organ Regulation (Urology), Osaka University Graduate School of Medicine
7 Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine
8 Department of Urology, Takahashi Clinic
9 Department of Comprehensive Kidney Disease Research, Osaka Graduate School of Medicine
10 Urology, Osaka University Graduate School of Medicine
11 Department of Geriatric Medicine & Nephrology, Osaka Graduate School of Medicine
12 Department of Advanced Technology for Transplantation, Osaka Graduate School of Medicine
?* Corresponding Author:
Takayuki Hamano, Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan hamatea at kid.med.osaka-u.ac.jp
Background and objective: Post-transplant malignancy (PTM) is a limiting factor both for patient and allograft survival in kidney transplant recipients (KTRs). We hypothesized that active vitamin D compounds (AVDs) could reduce PTM development in KTRs.
Design: Ambulatory KTRs in a Japanese prospective cohort were followed from August 2007 to November 2010. The outcome of interest was newly diagnosed PTM. A propensity score (PS) of having received AVDs was estimated using 26 clinically relevant factors. We used the Cox proportional hazards model with stratification by PS tertiles on the assumption that baseline hazard functions differ among tertiles. As sensitivity analyses, we used inverse probability weighting and PS matching.
Results: Among 218 participants, the median age was 50 (interquartile range [IQR], 40-59) years, 63.3% were male, median time since transplantation was 11.2 (IQR, 5.2-17.1) years, and mean estimated GFR was 41.3 (SD, 15.6) ml/min per 1.73 m2. At baseline, 42.2% had been treated with AVDs mainly for glucocorticoid-induced osteoporosis. AVDs used were calcitriol (58.7%) and alfacalcidol (41.3%). During follow-up, PTM developed in 5.4% of 92 AVD users and 8.7% of 126 non-users. Poor vitamin D status was common in the participants, but the serum 25-hydroxyvitamin D level was not significantly associated with PTM in Cox regression analysis.
After stratifying patients by PS tertiles, we found that AVDs were significantly associated with a lower risk of PTM (HR 0.25 [0.07-0.82]). Sensitivity analyses yielded similar results.
Conclusions: AVDs are potential chemopreventive agents against PTM in KTRs.
Received May 24, 2012, Revision received July 17, 2012; Accepted July 27, 2012.
Copyright © 2012, American Association for Cancer Research.
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