Interactions of sclerostin with FGF23, soluble klotho and vitamin D in renal transplantation

Tartaglione, Lida; Pasquali, Marzia; Rotondi, Silverio; Muci, Maria Luisa; Leonangeli, Cristiana; Farcomeni, Alessio; Fassino, Valeria; Mazzaferro, Sandro

doi:10.1371/journal.pone.0178637

Cited by 25 publications

(12 citation statements)

References 40 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three out of four assays also confirmed the previously reported positive correlation between plasma FGF23 levels and serum sclerostin levels in CKD patients [29,33], which as evidenced from experimental studies is due to the fact that sclerostin inhibits the protein-encoding gene PHEX [34]. PHEX reduces FGF23 activity by interacting with its co-receptor Klotho [33]. Inhibition of PHEX by sclerostin indirectly results in an increased tubular phosphate excretion and decreased 1,25 (OH) 2 Vit D synthesis via unhindered FGF23 activity.…”

Section: Demographic and Biochemical (Serum) Parameters In The Eskd Csupporting

confidence: 83%

Clinical Inference of Serum and Bone Sclerostin Levels in Patients with End-Stage Kidney Disease

Maré

Verhulst

Cavalier

et al. 2019

JCM

View full text Add to dashboard Cite

Mounting evidence indicates that sclerostin, a well-known inhibitor of bone formation, may qualify as a clinically relevant biomarker of chronic kidney disease-related mineral and bone disorder (CKD-MBD), including abnormal mineral and bone metabolism and extraskeletal calcification. For this purpose, in this study we investigate the extent to which circulating sclerostin, skeletal sclerostin expression, bone histomorphometric parameters, and serum markers of bone metabolism associate with each other. Bone biopsies and serum samples were collected in a cohort of 68 end-stage kidney disease (ESKD) patients. Serum sclerostin levels were measured using 4 different commercially available assays. Skeletal sclerostin expression was evaluated on immunohistochemically stained bone sections. Quantitative bone histomorphometry was performed on Goldner stained tissue sections. Different serum markers of bone metabolism were analyzed using in-house techniques or commercially available assays. Despite large inter-assay differences for circulating sclerostin, results obtained with the 4 assays under study closely correlated with each other, whilst moderate significant correlations with skeletal sclerostin expression were also found. Both skeletal and circulating sclerostin negatively correlated with histomorphometric bone and serum parameters reflecting bone formation and turnover. In this study, the unique combined evaluation of bone sclerostin expression, bone histomorphometry, bone biomarkers, and serum sclerostin levels, as assessed by 4 different assays, demonstrated that sclerostin may qualify as a clinically relevant marker of disturbed bone metabolism in ESKD patients.

show abstract

Section: Demographic and Biochemical (Serum) Parameters In The Eskd Csupporting

confidence: 83%

Clinical Inference of Serum and Bone Sclerostin Levels in Patients with End-Stage Kidney Disease

Maré

Verhulst

Cavalier

et al. 2019

JCM

View full text Add to dashboard Cite

show abstract

“…(7) Interestingly, previous literature has linked sclerostin with FGF23 in various disease models. Circulating levels of sclerostin and FGF23 are positively correlated in patients with sclerosteosis and in those with chronic kidney disease (10)(11)(12) and FGF23 levels are suppressed in the sclerostin null mouse. (13) Further, circulating sclerostin levels are higher in humans with XLH.…”

Section: Introductionmentioning

confidence: 99%

Sclerostin Antibody Treatment Increases Bone Mass and Normalizes Circulating Phosphate Levels in Growing Hyp Mice

Carpenter

Ross

2019

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

X‐linked hypophosphatemia (XLH), caused by a loss‐of‐function mutation in the phosphate regulating gene with homology to endopeptidase located on the X chromosome (PHEX), is the most common form of vitamin D‐resistant rickets. Loss of functional PHEX results in elevated fibroblast growth factor 23 (FGF23) levels, impaired phosphate reabsorption, and inhibited skeletal mineralization. Sclerostin, a protein produced primarily in osteocytes, suppresses bone formation by antagonizing Wnt signaling and is reported to be elevated in XLH patients. This study used the Hyp mouse model to investigate sclerostin's role in the pathophysiology of XLH by evaluating the use of a monoclonal antibody to sclerostin in a mouse model of XLH, the Hyp mouse. Male and female wild‐type and Hyp littermates were injected with 25 mg/kg of vehicle or sclerostin antibody (Scl‐Ab) twice weekly, beginning at 4 weeks of age and euthanized at 8 weeks of age. Scl‐Ab treatment increased serum phosphate levels and suppressed circulating levels of intact FGF23 in treated wild‐type and Hyp mice of both sexes. Cortical area, trabecular bone volume fraction (BV/TV), metaphyseal apparent density, and the peak load increased with Scl‐Ab treatment in both sexes. This short‐term treatment study suggests that Scl‐Ab treatment can effectively improve some of the pathologies associated with XLH, including normalization of phosphate, and that sclerostin may play a role in regulating FGF23 and phosphate metabolism in XLH. © 2019 American Society for Bone and Mineral Research.

show abstract

“…In addition, living donor KTx provides greater allograft longevity than those transplanted from a deceased donor [ 57 ]. However, changes in serum klotho levels and the impact of klotho on outcomes among KTx recipients and kidney donors remain unclear [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. Thus, we conducted this systematic review and meta-analysis to assess serum klotho levels and the impact of klotho on outcomes among KTx recipients and kidney donors…”

Section: Introductionmentioning

confidence: 99%

Serum Klotho in Living Kidney Donors and Kidney Transplant Recipients: A Meta-Analysis

Neyra

Hansrivijit

Medaura

et al. 2020

JCM

View full text Add to dashboard Cite

α-Klotho is a known anti-aging protein that exerts diverse physiological effects, including phosphate homeostasis. Klotho expression occurs predominantly in the kidney and is significantly decreased in patients with chronic kidney disease. However, changes in serum klotho levels and impacts of klotho on outcomes among kidney transplant (KTx) recipients and kidney donors remain unclear. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through October 2019 to identify studies evaluating serum klotho levels and impacts of klotho on outcomes among KTx recipients and kidney donors. Study results were pooled and analyzed utilizing a random-effects model. Ten cohort studies with a total of 431 KTx recipients and 5 cohort studies with a total of 108 living kidney donors and were identified. After KTx, recipients had a significant increase in serum klotho levels (at 4 to 13 months post-KTx) with a mean difference (MD) of 243.11 pg/mL (three studies; 95% CI 67.41 to 418.81 pg/mL). Although KTx recipients had a lower serum klotho level with a MD of = −234.50 pg/mL (five studies; 95% CI −444.84 to −24.16 pg/mL) compared to healthy unmatched volunteers, one study demonstrated comparable klotho levels between KTx recipients and eGFR-matched controls. Among kidney donors, there was a significant decrease in serum klotho levels post-nephrectomy (day 3 to day 5) with a mean difference (MD) of −232.24 pg/mL (three studies; 95% CI –299.41 to −165.07 pg/mL). At one year following kidney donation, serum klotho levels remained lower than baseline before nephrectomy with a MD of = −110.80 pg/mL (two studies; 95% CI 166.35 to 55.24 pg/mL). Compared to healthy volunteers, living kidney donors had lower serum klotho levels with a MD of = −92.41 pg/mL (two studies; 95% CI −180.53 to −4.29 pg/mL). There is a significant reduction in serum klotho levels after living kidney donation and an increase in serum klotho levels after KTx. Future prospective studies are needed to assess the impact of changes in klotho on clinical outcomes in KTx recipients and living kidney donors.

show abstract

Interactions of sclerostin with FGF23, soluble klotho and vitamin D in renal transplantation

Cited by 25 publications

References 40 publications

Clinical Inference of Serum and Bone Sclerostin Levels in Patients with End-Stage Kidney Disease

Clinical Inference of Serum and Bone Sclerostin Levels in Patients with End-Stage Kidney Disease

Sclerostin Antibody Treatment Increases Bone Mass and Normalizes Circulating Phosphate Levels in Growing Hyp Mice

Serum Klotho in Living Kidney Donors and Kidney Transplant Recipients: A Meta-Analysis

Contact Info

Product

Resources

About