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Research Article

Orally Active Vitamin D for Potential Chemoprevention of Posttransplant Malignancy

Yoshitsugu Obi, Naotsugu Ichimaru, Takayuki Hamano, Kodo Tomida, Isao Matsui, Naohiko Fujii, Masayoshi Okumi, Jun-ya Kaimori, Koji Yazawa, Yukito Kokado, Yoshiharu Tsubakihara, Norio Nonomura, Hiromi Rakugi, Shiro Takahara and Yoshitaka Isaka
Yoshitsugu Obi
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Naotsugu Ichimaru
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Takayuki Hamano
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Kodo Tomida
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Isao Matsui
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Naohiko Fujii
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Masayoshi Okumi
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Jun-ya Kaimori
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Koji Yazawa
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Yukito Kokado
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Yoshiharu Tsubakihara
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Norio Nonomura
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Hiromi Rakugi
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Shiro Takahara
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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Yoshitaka Isaka
Authors' Affiliations: Departments of 1Geriatric Medicine and Nephrology; 2Specific Organ Regulation (Urology), 3Advanced Technology for Transplantation, 4Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, Suita; 5Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka; 6Takahashi Clinic, Toyonaka, Osaka; and 7Department of Internal Medicine, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
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DOI: 10.1158/1940-6207.CAPR-12-0218 Published October 2012
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Abstract

Posttransplant malignancy (PTM) is a limiting factor both for patient and allograft survival in kidney transplant recipients (KTRs). We hypothesized that active vitamin D compounds (AVD) could reduce PTM development in KTRs. 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. Among 218 participants, the median age was 50 (interquartile range [IQR], 40 to 59) years, 63.3% were male, median time since transplantation was 11.2 (IQR, 5.2 to 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 nonusers. 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 to 0.82]). Sensitivity analyses yielded similar results. AVDs are potential chemopreventive agents against PTM in KTRs. Cancer Prev Res; 5(10); 1229–35. ©2012 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).

  • Received May 24, 2012.
  • Revision received July 17, 2012.
  • Accepted July 27, 2012.
  • ©2012 American Association for Cancer Research.
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Cancer Prevention Research: 5 (10)
October 2012
Volume 5, Issue 10
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Orally Active Vitamin D for Potential Chemoprevention of Posttransplant Malignancy
Yoshitsugu Obi, Naotsugu Ichimaru, Takayuki Hamano, Kodo Tomida, Isao Matsui, Naohiko Fujii, Masayoshi Okumi, Jun-ya Kaimori, Koji Yazawa, Yukito Kokado, Yoshiharu Tsubakihara, Norio Nonomura, Hiromi Rakugi, Shiro Takahara and Yoshitaka Isaka
Cancer Prev Res October 1 2012 (5) (10) 1229-1235; DOI: 10.1158/1940-6207.CAPR-12-0218

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Orally Active Vitamin D for Potential Chemoprevention of Posttransplant Malignancy
Yoshitsugu Obi, Naotsugu Ichimaru, Takayuki Hamano, Kodo Tomida, Isao Matsui, Naohiko Fujii, Masayoshi Okumi, Jun-ya Kaimori, Koji Yazawa, Yukito Kokado, Yoshiharu Tsubakihara, Norio Nonomura, Hiromi Rakugi, Shiro Takahara and Yoshitaka Isaka
Cancer Prev Res October 1 2012 (5) (10) 1229-1235; DOI: 10.1158/1940-6207.CAPR-12-0218
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