Soluble α-Klotho Serum Levels in Chronic Kidney Disease

Transmembrane α-Klotho (TM-Klotho), expressed in renal tubules, is a cofactor for FGF23-receptor. Circulating soluble-α-Klotho (s-Klotho) results from TM-Klotho shedding and acts on Phosphate (P) and Calcium (Ca) tubular transport. Decreased TM-Klotho, described in experimental chronic kidney diseas...

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Main Authors: Silverio Rotondi, Marzia Pasquali, Lida Tartaglione, Maria Luisa Muci, Giusy Mandanici, Cristiana Leonangeli, Silvia Sales, Alessio Farcomeni, Sandro Mazzaferro
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2015/872193
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author Silverio Rotondi
Marzia Pasquali
Lida Tartaglione
Maria Luisa Muci
Giusy Mandanici
Cristiana Leonangeli
Silvia Sales
Alessio Farcomeni
Sandro Mazzaferro
author_facet Silverio Rotondi
Marzia Pasquali
Lida Tartaglione
Maria Luisa Muci
Giusy Mandanici
Cristiana Leonangeli
Silvia Sales
Alessio Farcomeni
Sandro Mazzaferro
author_sort Silverio Rotondi
collection DOAJ
description Transmembrane α-Klotho (TM-Klotho), expressed in renal tubules, is a cofactor for FGF23-receptor. Circulating soluble-α-Klotho (s-Klotho) results from TM-Klotho shedding and acts on Phosphate (P) and Calcium (Ca) tubular transport. Decreased TM-Klotho, described in experimental chronic kidney disease (CKD), prevents actions of FGF23 and lessens circulating s-Klotho. Thus, levels of s-Klotho could represent a marker of CKD-MBD. To evaluate the clinical significance of s-Klotho in CKD we assayed serum s-Klotho and serum FGF23 in 68 patients (age 58±15; eGFR 45±21 mL/min). s-Klotho was lower than normal (519±183 versus 845±330 pg/mL, P<.0001) in renal patients and its reduction was detectable since CKD stage 2 (P<.01). s-Klotho correlated positively with eGFR and serum calcium (Cas) and negatively with serum phosphate (Ps), PTH and FGF23. FGF23 was higher than normal (73±51 versus 36±11, P<.0002) with significantly increased levels since CKD stage 2 (P<.001). Our data indicate a negative effect of renal disease on circulating s-Klotho starting very early in CKD. Assuming that s-Klotho mirrors TM-Klotho synthesis, low circulating s-Klotho seems to reflect the ensuing of tubular resistance to FGF23, which, accordingly, is increased. We endorse s-Klotho as an early marker of CKD-MBD.
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spelling doaj-art-daf1083537c742b0bc6b68376e9e868f2025-08-20T03:24:25ZengWileyInternational Journal of Endocrinology1687-83371687-83452015-01-01201510.1155/2015/872193872193Soluble α-Klotho Serum Levels in Chronic Kidney DiseaseSilverio Rotondi0Marzia Pasquali1Lida Tartaglione2Maria Luisa Muci3Giusy Mandanici4Cristiana Leonangeli5Silvia Sales6Alessio Farcomeni7Sandro Mazzaferro8Department of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, “Sapienza” University, 5 Piazzale Aldo Moro, 00185 Rome, ItalyDepartment of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, “Sapienza” University, 5 Piazzale Aldo Moro, 00185 Rome, ItalyDepartment of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, “Sapienza” University, 5 Piazzale Aldo Moro, 00185 Rome, ItalyDepartment of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, “Sapienza” University, 5 Piazzale Aldo Moro, 00185 Rome, ItalyDepartment of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, “Sapienza” University, 5 Piazzale Aldo Moro, 00185 Rome, ItalyDepartment of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, “Sapienza” University, 5 Piazzale Aldo Moro, 00185 Rome, ItalyDepartment of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, “Sapienza” University, 5 Piazzale Aldo Moro, 00185 Rome, ItalyDepartment of Public Health and Infectious Diseases, Section of Statistics, “Sapienza” University, 5 Piazzale Aldo Moro, 00185 Rome, ItalyDepartment of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, “Sapienza” University, 5 Piazzale Aldo Moro, 00185 Rome, ItalyTransmembrane α-Klotho (TM-Klotho), expressed in renal tubules, is a cofactor for FGF23-receptor. Circulating soluble-α-Klotho (s-Klotho) results from TM-Klotho shedding and acts on Phosphate (P) and Calcium (Ca) tubular transport. Decreased TM-Klotho, described in experimental chronic kidney disease (CKD), prevents actions of FGF23 and lessens circulating s-Klotho. Thus, levels of s-Klotho could represent a marker of CKD-MBD. To evaluate the clinical significance of s-Klotho in CKD we assayed serum s-Klotho and serum FGF23 in 68 patients (age 58±15; eGFR 45±21 mL/min). s-Klotho was lower than normal (519±183 versus 845±330 pg/mL, P<.0001) in renal patients and its reduction was detectable since CKD stage 2 (P<.01). s-Klotho correlated positively with eGFR and serum calcium (Cas) and negatively with serum phosphate (Ps), PTH and FGF23. FGF23 was higher than normal (73±51 versus 36±11, P<.0002) with significantly increased levels since CKD stage 2 (P<.001). Our data indicate a negative effect of renal disease on circulating s-Klotho starting very early in CKD. Assuming that s-Klotho mirrors TM-Klotho synthesis, low circulating s-Klotho seems to reflect the ensuing of tubular resistance to FGF23, which, accordingly, is increased. We endorse s-Klotho as an early marker of CKD-MBD.http://dx.doi.org/10.1155/2015/872193
spellingShingle Silverio Rotondi
Marzia Pasquali
Lida Tartaglione
Maria Luisa Muci
Giusy Mandanici
Cristiana Leonangeli
Silvia Sales
Alessio Farcomeni
Sandro Mazzaferro
Soluble α-Klotho Serum Levels in Chronic Kidney Disease
International Journal of Endocrinology
title Soluble α-Klotho Serum Levels in Chronic Kidney Disease
title_full Soluble α-Klotho Serum Levels in Chronic Kidney Disease
title_fullStr Soluble α-Klotho Serum Levels in Chronic Kidney Disease
title_full_unstemmed Soluble α-Klotho Serum Levels in Chronic Kidney Disease
title_short Soluble α-Klotho Serum Levels in Chronic Kidney Disease
title_sort soluble α klotho serum levels in chronic kidney disease
url http://dx.doi.org/10.1155/2015/872193
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