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.
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 humanerythropoietin (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.
Authors: M Kuro-o; Y Matsumura; H Aizawa; H Kawaguchi; T Suga; T Utsugi; Y Ohyama; M Kurabayashi; T Kaname; E Kume; H Iwasaki; A Iida; T Shiraki-Iida; S Nishikawa; R Nagai; Y I Nabeshima Journal: Nature Date: 1997-11-06 Impact factor: 49.962
Authors: Ivana Pavik; Philippe Jaeger; Lena Ebner; Carsten A Wagner; Katja Petzold; Daniela Spichtig; Diane Poster; Rudolf P Wüthrich; Stefan Russmann; Andreas L Serra Journal: Nephrol Dial Transplant Date: 2012-11-04 Impact factor: 5.992
Authors: Chul Woo Yang; Can Li; Ju Young Jung; Seok Joon Shin; Bum Soon Choi; Sun Woo Lim; Bo Kyung Sun; Yong Soo Kim; Jin Kim; Yoon Sik Chang; Byung Kee Bang Journal: FASEB J Date: 2003-07-18 Impact factor: 5.191
Authors: Charat Thongprayoon; Javier A Neyra; Panupong Hansrivijit; Juan Medaura; Napat Leeaphorn; Paul W Davis; Wisit Kaewput; Tarun Bathini; Sohail Abdul Salim; Api Chewcharat; Narothama Reddy Aeddula; Saraschandra Vallabhajosyula; Michael A Mao; Wisit Cheungpasitporn Journal: J Clin Med Date: 2020-06-12 Impact factor: 4.241
Authors: Przemyslaw Solek; Jennifer Mytych; Ewelina Sujkowska; Magdalena Grzegorczyk; Patrycja Jasiewicz; Magdalena Sowa-Kucma; Katarzyna Stachowicz; Marek Koziorowski; Anna Tabecka-Lonczynska Journal: Toxicol Res Date: 2021-05-20