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Influence of conversion from calcineurin inhibitors to everolimus on fibrosis, inflammation, tubular damage and vascular function in renal transplant patients

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Abstract

Background

Conversion from calcineurin inhibitor (CNI) to mTOR inhibitors may reduce and even halt the progression of chronic allograft dysfunction (CAD) which is the most important cause of renal allograft loss. We aimed to investigate the effects of conversion from CNI to everolimus on parameters of fibrosis, inflammation, glomerulotubular damage and vascular functions in renal transplant recipients.

Methods

Fifteen stable renal transplant recipients who were under CNI treatment (male/female 13/2, mean age 41 ± 10 years) were enrolled and switched to everolimus. Serum and urinary transforming growth factor-β (TGF-β), urinary neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein-1 (MCP-1) were measured as markers of fibrosis, tubular damage and inflammation. As parameters of vascular functions, pulse wave velocity (PWV), augmentation index (AIx), serum asymmetric dimethyl-arginine and fibroblast growth factor-23 (FGF-23) were measured. All these measurements were repeated at the 3rd month of conversion.

Results

Estimated GFR (52 ± 7–57 ± 11 ml/min/l.73 m2, p = 0.02) (was increased after conversion to everolimus. However, serum uric acid levels were significantly decreased (6.21 ± 1.21–5.50 ± 1.39 mg/dL, p = 0.01). Serum TGF-β levels (8727 ± 2897–1943 ± 365 pg/mL, p = 0.03) and urinary NGAL levels (26 ± 10–12 ± 2 ng/mg creatinine, p = 0.05) were significantly decreased. However, urinary MCP-1, FGF-23, PWV and AIx did not change. Urinary TGF-β was associated with urinary NGAL (r = 0.62, p = 0.01), urinary MCP-1 (r = 0.68, p = 0.005) and proteinuria (r = 0.50, p = 0.05).

Conclusion

Conversion from CNI to everolimus resulted in significant decreases of serum TGF-β and urinary NGAL which may represent less fibrosis and tubular damage. Association of urinary TGF-β with NGAL and MCP-1 suggests that tubular damage, fibrosis and inflammation may act together for progression of CAD.

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Acknowledgements

This study was presented in American Transplant Congress in 18–22 May 2013. This study has been supported by Istanbul University Research Foundation with grant number 2012/827-1068.

Conflict of interest

All the authors have declared no competing interest.

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Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul School of Medicine, Istanbul University, Fatih, 34093, Istanbul, Turkey

    Nadir Alpay, Yasar Caliskan, Tulin Akagun & Alaattin Yildiz

  2. Department of Internal Medicine and Nephrology, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey

    Abdullah Ozkok

  3. Experimental Medical Research Institute, Istanbul University, Istanbul, Turkey

    Suzan Adın Cinar & Gunnur Deniz

  4. Medicana International Hospital, Istanbul, Turkey

    Muzaffer Sariyar & Alaattin Yildiz

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  1. Nadir Alpay
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Correspondence to Alaattin Yildiz.

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Alpay, N., Ozkok, A., Caliskan, Y. et al. Influence of conversion from calcineurin inhibitors to everolimus on fibrosis, inflammation, tubular damage and vascular function in renal transplant patients. Clin Exp Nephrol 18, 961–967 (2014). https://doi.org/10.1007/s10157-014-0939-4

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