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NDT Advance Access published online on March 18, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp117
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Active vitamin D and its analogue, 22-oxacalcitriol, ameliorate puromycin aminonucleoside-induced nephrosis in rats

Isao Matsui1, Takayuki Hamano1, Kodo Tomida1, Kazunori Inoue1, Yoshitsugu Takabatake1, Yasuyuki Nagasawa1, Noritaka Kawada1, Takahito Ito1, Hiroshi Kawachi2, Hiromi Rakugi1, Enyu Imai1 and Yoshitaka Isaka1

1 Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka 2 Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

Correspondence and offprint requests to: Takayuki Hamano; E-mail: hamatea{at}medone.med.osaka-u.ac.jp



  Abstract

Background. Recent studies have demonstrated that podocyte injury, which results in proteinuria, leads to tubulointerstitial fibrosis. Although some studies have revealed that vitamin D administration protects renal structure and function in mesangial cell proliferative and/or excessive matrix productive models, the effects of vitamin D on podocyte injury have remained uncertain.

Methods. In this study, we examined whether administration of active vitamin D (calcitriol) or its analogue, 22-oxacalcitriol (maxacalcitol), is preventative in podocyte injury using the puromycin aminonucleoside nephrosis model with neither mesangial proliferation nor matrix accumulation.

Results. Before the onset of proteinuria, renal 1{alpha}-hydroxylase and 24-hydroxylase were markedly down-regulated and up-regulated, respectively, leading to impaired vitamin D activation. Thereafter, serum 25-hydroxyvitamin D decreased along with the increased excretion of vitamin D-binding protein in urine. After confirming that podocytes express vitamin D receptor and all retinoid X receptors (RXRs) except RXR-{alpha}, we found that daily administration of calcitriol or its analogue 22-oxacalcitriol ameliorated the nephrotic state by protecting podocytes, as shown by the reduced staining of desmin (podocyte injury marker) and the upregulation of nephrin and podocin. These data suggest that the impairment of the vitamin D system plays a role in increasing proteinuria in podocyte injury.

Conclusions. We demonstrated the breakdown of the vitamin D activation system in podocyte injury, and established a preventative role for vitamin D in podocyte injury.

Keywords: calcitriol; maxacalcitol; nephrin; podocyte; proteinuria

Received for publication: 13.11.08
Accepted in revised form: 25. 2.09


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