Kidney Week

Abstract: FR-PO899

Mammalian Target of Rapamycin (mTOR) Inhibitor Might Augment Klotho Levels of Kidney Transplant Recipients

Session Information

• Transplantation: Translational and Transplant Pathology
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1802 Transplantation: Clinical

Authors

• Hasuike, Yukiko, Hyogo College of Medicine, Nishinomiya City, Hyōgo, Japan

Yukiko Hasuike,

• Mizusaki, Kosuke, Hyogo College of Medicine, Nishinomiya City, Hyōgo, Japan

Kosuke Mizusaki,

• Kimura, Tomoko, Hyogo College of Medicine, Nishinomiya City, Hyōgo, Japan

Tomoko Kimura,

• Nagasawa, Yasuyuki, Hyogo College of Medicine, Nishinomiya City, Hyōgo, Japan

Yasuyuki Nagasawa,

• Kuragano, Takahiro, Hyogo College of Medicine, Nishinomiya City, Hyōgo, Japan

Takahiro Kuragano,

• Yamada, Yusuke, Hyogo College of Medicine, Nishinomiya, Hyōgo, Japan

Yusuke Yamada,

• Nojima, Michio, Hyogo College of Medicine, Nishinomiya, Hyōgo, Japan

Michio Nojima,

• Yamamoto, Shingo, Hyogo College of Medicine, Nishinomiya, Hyōgo, Japan

Shingo Yamamoto,

• Ishihara, Masaharu, Hyogo College of Medicine, Nishinomiya City, Hyōgo, Japan

Masaharu Ishihara,

Background

α-Klotho, an anti-aging kidney-secreted hormone, exists in several forms including the membrane and a soluble form (sKlotho). sKlotho level of chronic kidney disease (CKD) patients is reduced. sKlotho administration attenuated renal fibrosis and dysfunction. It was reported that mTOR inhibitor reduce interstitial fibrosis and glomerular sclerosis of kidney transplantation (TPL) recipients, however, the mechanism is unclear. We investigated the influence of mTOR inhibitor on sKlotho of CKD patients before and after TPL.

Methods

This was a retrospective, observational study of kidney TPL recipients who were treated in Kidney Transplant Center of Hyogo College of Medicine (from 2001 July to 2016 October). Blood samples were collected before and 1-year after TPL and stored until assay. Serum sKlotho and fibroblast growth factor (FGF)-23 concentrations were measured using human ELISA, respectively. Several factors related to CKD (Ca, iP, intact parathyroid hormone, and 1,25(OH)₂vitamin D) were examined.

Results

The CKD patients (n=36) were participated. Median age and vintage of participants was 37.0 (IQR, 27.5-50.5) y.o. and 4.6 (1.0-8.8) years. In this study, 75.0% (n=27) of kidney TPL were living donor, 8.3% (n=3) were received preemptive TPL, and 36.1% (n=13) were administrated mTOR inhibitor (everolimus). Comparing before and after TPL, sKlotho level was significantly increased (p<0.001) and FGF23 level was decreased (p<0.001). After TPL, sKlotho level of participants with mTOR inhibitor was significantly higher than that without mTOR inhibitor, 537 (367-659) pg/ml vs 332.4 (250-550) pg/ml (p=0.026, Figure 1). There was no significant difference of the other parameters between before and after TPL.

Conclusion

Administration of mTOR inhibitor might augment Klotho level of CKD patients after TPL.