title: Soluble α -Klotho Serum Levels in Chronic Kidney Disease.
abstract: 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.
authors: Department of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, "Sapienza" University, 5 Piazzale Aldo Moro, 00185 Rome, Italy.
authors: Silverio
authors: 0000-0003-4553-1756
authors: S
authors: Rotondi
authors: Department of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, "Sapienza" University, 5 Piazzale Aldo Moro, 00185 Rome, Italy.
authors: Marzia
authors: M
authors: Pasquali
authors: Department of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, "Sapienza" University, 5 Piazzale Aldo Moro, 00185 Rome, Italy.
authors: Lida
authors: 0000-0003-4537-0876
authors: L
authors: Tartaglione
authors: Department of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, "Sapienza" University, 5 Piazzale Aldo Moro, 00185 Rome, Italy.
authors: Maria Luisa
authors: ML
authors: Muci
authors: Department of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, "Sapienza" University, 5 Piazzale Aldo Moro, 00185 Rome, Italy.
authors: Giusy
authors: G
authors: Mandanici
authors: Department of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, "Sapienza" University, 5 Piazzale Aldo Moro, 00185 Rome, Italy.
authors: Cristiana
authors: 0000-0001-9562-3742
authors: C
authors: Leonangeli
authors: Department of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, "Sapienza" University, 5 Piazzale Aldo Moro, 00185 Rome, Italy.
authors: Silvia
authors: S
authors: Sales
authors: Department of Public Health and Infectious Diseases, Section of Statistics, "Sapienza" University, 5 Piazzale Aldo Moro, 00185 Rome, Italy.
authors: Alessio
authors: 0000-0002-7104-5826
authors: A
authors: Farcomeni
authors: Department of Cardiovascular, Respiratory, Nephrology, Geriatric, and Anesthetic Sciences, "Sapienza" University, 5 Piazzale Aldo Moro, 00185 Rome, Italy.
authors: Sandro
authors: S
authors: Mazzaferro