Walter Reinhardt1, Sebastian Dolff1, Sven Benson2, Martina Broecker-Preuß3, Stefan Behrendt1, Antonia Hög4, Dagmar Führer3, Lutz Schomburg4, Josef Köhrle4. 1. 1 Department of Nephrology, University Hospital Essen, University Duisburg-Essen , Germany . 2. 2 Institute of Medical Psychology and Behavioral Immunobiology, University Clinic Essen, University Duisburg-Essen , Germany . 3. 3 Department of Endocrinology and Metabolism and Division of Laboratory Research, University Duisburg-Essen , Germany . 4. 4 Institut für Experimentelle Endokrinologie, Charite-Universitätsmedizin , Berlin, Germany .
Abstract
INTRODUCTION: Chronic kidney disease (CKD) impairs thyroid hormone (TH) metabolism and is associated with low serum triiodothyronine (T3) concentrations in patients with a low glomerular filtration rate (GFR). Whether this results from decreased T3 formation from thyroxine (T4) by impaired 5'-deiodinase (DIO) activity and/or enhanced degradation of T3 and increased reverse triiodothyronine (rT3) formation from T4 by elevated 5-DIO activity remains unclear. Both activating 5'- and the inactivating 5-deiodination of TH are catalyzed by three selenium (Se)-dependent DIO isoenzymes. Selenoprotein P (SePP) is the major constituent of serum selenium, and functions as Se transport protein from liver to kidney and several other organs. This study tested the hypothesis that serum SePP and TH status are associated with the degree of renal impairment in patients with CKD. PATIENTS AND METHODS: A total of 180 CKD patients (stages 1-5) and 70 chronic hemodialysis (CHD) patients undergoing hemodialysis three times per week for at least two years were prospectively investigated for clinical data, parameters of renal function, serum TH profile (thyrotropin, T4, free thyroxine [fT4], T3, free triiodothyronine (fT3), rT3, thyroxine-binding globulin [TBG]), C-reactive protein (CRP), and serum SePP. RESULTS: In CKD patients, renal function was negatively associated with SePP concentration (standardized β = -0.17, p = 0.029); that is, SePP concentrations increased in more advanced CKD stages. In contrast, significantly lower SePP concentrations were found in patients on hemodialysis compared with CKD patients (M ± SD = 2.7 ± 0.8 mg/L vs. 3.3 ± .9 mg/L; p < 0.001). Notably, in CKD patients, the SePP concentration was negatively associated with T4 (standardized β = -0.16, p = 0.039) and fT4 (standardized β = -0.16, p = 0.039) concentrations, but no association was found with T3, fT3, rT3, T3/T4, rT3/T3, rT3/T4, or TBG concentrations. The SePP concentration was also negatively associated with CRP levels (standardized β = -0.17, p = 0.029). In the CHD group, no association was detected between SePP and the investigated TH parameters. SUMMARY AND CONCLUSION: Impaired renal function is positively correlated with serum concentrations of SePP. In patients undergoing CHD treatment, SePP concentrations were significantly reduced, but the TH profile remained unaffected. These findings indicate an important contribution of kidney function on serum SePP homeostasis, and consequently on Se status.
INTRODUCTION:Chronic kidney disease (CKD) impairs thyroid hormone (TH) metabolism and is associated with low serum triiodothyronine (T3) concentrations in patients with a low glomerular filtration rate (GFR). Whether this results from decreased T3 formation from thyroxine (T4) by impaired 5'-deiodinase (DIO) activity and/or enhanced degradation of T3 and increased reverse triiodothyronine (rT3) formation from T4 by elevated 5-DIO activity remains unclear. Both activating 5'- and the inactivating 5-deiodination of TH are catalyzed by three selenium (Se)-dependent DIO isoenzymes. Selenoprotein P (SePP) is the major constituent of serum selenium, and functions as Se transport protein from liver to kidney and several other organs. This study tested the hypothesis that serum SePP and TH status are associated with the degree of renal impairment in patients with CKD. PATIENTS AND METHODS: A total of 180 CKDpatients (stages 1-5) and 70 chronic hemodialysis (CHD) patients undergoing hemodialysis three times per week for at least two years were prospectively investigated for clinical data, parameters of renal function, serum TH profile (thyrotropin, T4, free thyroxine [fT4], T3, free triiodothyronine (fT3), rT3, thyroxine-binding globulin [TBG]), C-reactive protein (CRP), and serum SePP. RESULTS: In CKDpatients, renal function was negatively associated with SePP concentration (standardized β = -0.17, p = 0.029); that is, SePP concentrations increased in more advanced CKD stages. In contrast, significantly lower SePP concentrations were found in patients on hemodialysis compared with CKDpatients (M ± SD = 2.7 ± 0.8 mg/L vs. 3.3 ± .9 mg/L; p < 0.001). Notably, in CKDpatients, the SePP concentration was negatively associated with T4 (standardized β = -0.16, p = 0.039) and fT4 (standardized β = -0.16, p = 0.039) concentrations, but no association was found with T3, fT3, rT3, T3/T4, rT3/T3, rT3/T4, or TBG concentrations. The SePP concentration was also negatively associated with CRP levels (standardized β = -0.17, p = 0.029). In the CHD group, no association was detected between SePP and the investigated TH parameters. SUMMARY AND CONCLUSION: Impaired renal function is positively correlated with serum concentrations of SePP. In patients undergoing CHD treatment, SePP concentrations were significantly reduced, but the TH profile remained unaffected. These findings indicate an important contribution of kidney function on serum SePP homeostasis, and consequently on Se status.
Authors: Walter Reinhardt; Nils Mülling; Stefan Behrendt; Sven Benson; Sebastian Dolff; Dagmar Führer; Susanne Tan Journal: Endocrine Date: 2021-02-11 Impact factor: 3.633