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Tolvaptan, a selective oral vasopressin V2 receptor antagonist, ameliorates podocyte injury in puromycin aminonucleoside nephrotic rats

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Abstract

Background

Proteinuria caused by glomerular disease is characterized by podocyte injury. Vasopressin V2 receptor antagonists are effective in reducing albuminuria, although their actions on glomerular podocytes have not been explored. The objective of this study was to evaluate the effects of tolvaptan, a selective oral V2 receptor antagonist, on podocytes in a puromycin aminonucleoside (PAN)-induced nephrosis rat model.

Methods

Rats were allocated to a control, PAN nephrosis, or tolvaptan-treated PAN nephrosis group (n = 9 per group). Urinary protein excretion and serum levels of total protein, albumin, creatinine, and total cholesterol were measured on day 10. The influence of tolvaptan on podocytes was examined in renal tissues by immunofluorescence and electron microscopy.

Results

PAN induced massive proteinuria and serum creatinine elevation on day 10, both of which were significantly ameliorated by tolvaptan. Immunofluorescence studies of the podocyte-associated proteins nephrin and podocin revealed granular staining patterns in PAN nephrosis rats. In tolvaptan-treated rats, nephrin and podocin expressions retained their normal linear pattern. Electron microscopy showed foot process effacement was ameliorated in tolvaptan-treated rats.

Conclusions

Tolvaptan is protective against podocyte damage and proteinuria in PAN nephrosis. This study indicates that tolvaptan exerts a renoprotective effect by affecting podocyte morphology and probably function in PAN nephrosis. Tolvaptan is a promising pharmacological tool in the treatment of renal edema.

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Acknowledgments

We thank Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan for providing tolvaptan.

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Authors and Affiliations

  1. Division of Nephrology and Blood Purification Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-0012, Japan

    Tadashi Okada, Toshifumi Sakaguchi, Fumie Saji, Shigeo Negi, Haruhisa Otani & Takashi Shigematsu

  2. First Department of Pathology, Wakayama Medical University, Wakayama, Japan

    Ikuji Hatamura & Yasuteru Muragaki

  3. Ryoshukai Wakayama Kidney Disease Clinic, Wakayama, Japan

    Haruhisa Otani

  4. Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Hiroshi Kawachi

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  1. Tadashi Okada
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  2. Toshifumi Sakaguchi
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  4. Fumie Saji
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  5. Shigeo Negi
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  7. Yasuteru Muragaki
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  8. Hiroshi Kawachi
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  9. Takashi Shigematsu
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Correspondence to Tadashi Okada.

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Okada, T., Sakaguchi, T., Hatamura, I. et al. Tolvaptan, a selective oral vasopressin V2 receptor antagonist, ameliorates podocyte injury in puromycin aminonucleoside nephrotic rats. Clin Exp Nephrol 13, 438–446 (2009). https://doi.org/10.1007/s10157-009-0196-0

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  • DOI: https://doi.org/10.1007/s10157-009-0196-0

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