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Soluble Klotho levels in adult renal transplant recipients are modulated by recombinant human erythropoietin

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Abstract

Background

Data on serum soluble Klotho levels in chronic kidney disease are contradictory and even less is known after renal transplantation. Experimental studies demonstrated that recombinant human erythropoietin (rhEPO) treatment mitigates Klotho reduction caused by renal damage. Therefore, this study aimed to determine serum Klotho levels in a cohort of kidney transplant recipients (KTR) and to evaluate whether rhEPO treatment can modulate, in vivo and in vitro, soluble Klotho.

Methods

117 KTR and 22 healthy subjects (HS) were enrolled. In 17 KTR, rhEPO was discontinued for 5 weeks and Klotho levels were compared to 34 propensity score-matched controls. Moreover, we evaluated Klotho mRNA expression and protein secretion in HK-2 tubular cells treated with cyclosporin A (CyA) and rhEPO, alone or in combination.

Results

Serum Klotho levels in KTR were significantly higher than in HS (0.68 vs. 0.37, p = 0.002) and significantly associated with estimated glomerular filtration rate (r = −0.378, p = 0.003) and fibroblast growth factor 23 (r = −0.307, p < 0.0001). After 5 weeks of rhEPO discontinuation, treated KTR showed a sharper reduction of Klotho levels than controls (−0.56 vs. −0.11 ng/ml, p < 0.0001). In HK-2 cells CyA treatment induced a Klotho down-regulation that was mitigated by rhEPO pre-treatment. In the same experimental conditions, our results revealed that cells treated with CyA + rhEPO secreted higher soluble Klotho levels than those exposed to CyA or rhEPO alone.

Conclusions

Our results demonstrate that KTR have higher serum Klotho levels than HS and that rhEPO treatment modulates these concentrations, suggesting a link between rhEPO and soluble Klotho in KTR.

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Acknowledgments

The study was supported by SIN (Italian Society of Nephrology), AMGEN

Conflict of interest

All the authors declared no competing interests. The manuscript has been seen and approved by all authors and it is not under consideration for publication elsewhere in a similar form, in any language

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Authors and Affiliations

  1. Kidney and Transplantation Research Center, “Annunziata” Hospital, via F. Migliori, 87100, Cosenza, Italy

    Francesca Leone, Danilo Lofaro, Paolo Gigliotti, Anna Perri, Donatella Vizza, Giuseppina Toteda, Simona Lupinacci, Filomena Armentano, Teresa Papalia & Renzo Bonofiglio

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  1. Francesca Leone
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  2. Danilo Lofaro
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  3. Paolo Gigliotti
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  4. Anna Perri
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  10. Renzo Bonofiglio
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Correspondence to Renzo Bonofiglio.

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Leone, F., Lofaro, D., Gigliotti, P. et al. Soluble Klotho levels in adult renal transplant recipients are modulated by recombinant human erythropoietin. J Nephrol 27, 577–585 (2014). https://doi.org/10.1007/s40620-014-0089-5

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  • DOI: https://doi.org/10.1007/s40620-014-0089-5

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