Laboratory aspects of circulating  -Klotho

Heijboer, Annemieke C.; Blankenstein, Marinus A.; Hoenderop, Joost G. J.; Borst, Martin H. de; Vervloet, Marc G.

doi:10.1093/ndt/gft236

Cited by 80 publications

(64 citation statements)

References 22 publications

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“…Klotho levels in the serum were analyzed using an aklotho ELISA kit (Immuno-Biological Laboratories Co, Japan) as described before. The kit has been validated and has been widely used for the measurement of klotho levels [15,16,28,29]. The intraassay coefficiency of variation (CV) ranged from 3% to 3.5%, and the inter-assay CV ranged from 3.7 to 8.1%.…”

Section: Laboratory Measurementsmentioning

confidence: 99%

Alteration in serum klotho levels in anorexia nervosa patients

et al. 2016

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Section: Laboratory Measurementsmentioning

confidence: 99%

Alteration in serum klotho levels in anorexia nervosa patients

et al. 2016

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“…None of the current ELISA methods for measuring FGF23 and sKlotho have been subject to international standardisation and show poor agreement (35,36 52.0-72.0 ml/min per 1.73 m 2 ). By including a control group of patients matched for eGFR, we found a trend towards higher iFGF23 levels and lower sKlotho levels in the kidney transplant patients not attributable to reduced graft function.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Soluble Klotho and intact fibroblast growth factor 23 in long-term kidney transplant patients

Bleskestad

Thorsen

Jonsson

et al. 2015

European Journal of Endocrinology

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Background: Controversies exist whether disturbances in mineral and bone disorder (MBD) normalise or persist after kidney transplantation. We assessed markers of MBD in patients with well-functioning kidney transplants to minimise confounding by reduced transplant function. Methods: In this cross-sectional study, 40 patients aged R18 years who received a first kidney transplant more than 10 years ago were included. A well-functioning transplant was defined as an estimated glomerular filtration rate (eGFR) R45 ml/min per 1.73 m 2 .

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“…to determine TNF484-induced effects on systemic klotho levels, since the reliability of currently available assays to measure systemic klotho levels are controversial (14). Nevertheless, our in vitro data indicate that ADAM/MMP inhibition indeed has klotho-dependent effects.…”

Section: Discussionmentioning

confidence: 78%

Shedding of klotho by ADAMs in the kidney

Loon

Pulskens

Hagen

et al. 2015

American Journal of Physiology-Renal Physiology

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The anti-aging gene klotho plays an important role in Ca 2ϩ and phosphate homeostasis. Membrane-bound klotho is an essential coreceptor for fibroblast growth factor-23 and can be cleaved by proteases, including a disintegrin and metalloproteinase (ADAM)10 and ADAM17. Cleavage of klotho occurs at a site directly above the plasma membrane (␣-cut) or between the KL1 and KL2 domain (␤-cut), resulting in soluble full-length klotho or KL1 and KL2 fragments, respectively. The aim of the present study was to gain insights into the mechanisms behind klotho cleavage processes in the kidney. Klotho shedding was demonstrated using a Madin-Darby canine kidney cell line stably expressing klotho and human embryonic kidney-293 cells transiently transfected with klotho. Here, we report klotho expression on both the basolateral and apical membrane, with a higher abundance of klotho at the apical membrane and in the apical media. mRNA expression of ADAM17 and klotho were enriched in mouse distal convoluted and connecting tubules. In vitro ADAM/matrix metalloproteinase inhibition by TNF484 resulted in a concentration-dependent inhibition of the ␣-cut, with a less specific effect on ␤-cut shedding. In vivo TNF484 treatment in wild-type mice did not change urinary klotho levels. However, ADAM/matrix metalloproteinase inhibition did increase renal and duodenal mRNA expression of phosphate transporters, whereas serum phosphate levels were significantly decreased. In conclusion, our data show that renal cells preferentially secrete klotho to the apical side and suggest that ADAMs are responsible for ␣-cut cleavage.klotho; a disintegrin and metalloproteinase 10; a disintegrin and metalloproteinase 17; klotho shedding; a disintegrin and metalloproteinase/matrix metalloproteinase inhibitor CA 2ϩ AND PHOSPHATE HOMEOSTASIS is a tightly regulated process involving several hormones. Klotho is emerging as a key factor in this process (5,18,51). Initially, the klotho gene was discovered as an anti-aging gene, since lack of klotho in mice resulted in early aging and a premature death (23, 26), whereas overexpression of klotho led to an increased lifespan (28).Klotho is a single-pass type 1 transmembrane protein consisting of two extracellular domains, which are the KL1 and KL2 subunits. Full-length klotho has potential enzymatic activity (30, 49), and in the body, it exists in two forms, namely, membrane-bound and soluble klotho. Membrane-bound klotho is predominantly present in the renal distal convolution, consisting of the distal convoluted tubule (DCT) and connecting tubule (CNT), parathyroid glands, and choroid plexus in the brain (26,31). A key function of membrane-bound klotho is to act as an obligate cofactor for the fibroblast growth factor (FGF) receptor, thereby enabling binding and downstream signaling of FGF23 via the ERK1/2 MAPK pathway (27, 51). In the kidney, binding of FGF23 to the receptor complex results in enhanced phosphate excretion via reduced expression of the Na ϩ -phosphate transporters NaPi-IIa and NaPiIIc (12). Moreov...

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Laboratory aspects of circulating -Klotho

Abstract: The commercially available methods for the measurement of α-Klotho differ in quality. Some of the manufacturers should improve their assays in order to produce accurate results so that reliable conclusions can be drawn from studies in which these assays are used.

Cited by 80 publications

References 22 publications

Alteration in serum klotho levels in anorexia nervosa patients

Alteration in serum klotho levels in anorexia nervosa patients

Soluble Klotho and intact fibroblast growth factor 23 in long-term kidney transplant patients

Shedding of klotho by ADAMs in the kidney

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