The Relation between Renal Function and Serum Sclerostin in Adult Patients with CKD

Pelletier, Solenne; Dubourg, Laurence; Carlier, Marie-Christine; Hadj‐Aïssa, Aoumeur; Fouque, Denis

doi:10.2215/cjn.07670712

Cited by 184 publications

(178 citation statements)

References 22 publications

(24 reference statements)

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“…Sclerostin has been shown to be increased in CKD-5D patients (38). A strong inverse relationship was observed between GFR and serum sclerostin (39). Our findings show that bone loss can be predicted by elevated serum levels of sclerostin in patients with CKD-5D.…”

Section: Discussionsupporting

confidence: 53%

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Malluche¹,

Davenport

Cantor³

et al. 2014

Clinical Journal of the American Society of Nephrology

122

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Background and objectives Use of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is controversial for diagnosing bone loss in CKD patients on dialysis. The alternative quantitative computed tomography (QCT) is expensive and requires high radiation exposure. This study compared the two techniques and evaluated serum biochemical parameters for prediction of bone loss.Design, setting, participants, & measurements This prospective study enrolled patients from dialysis centers throughout Kentucky. BMD of the spine and hip was measured at baseline and after 1 year by DXA and QCT. Customary and novel serum biochemical parameters were obtained at the same times, including calcium, phosphorus, whole and intact parathyroid hormone, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide, tartrate-resistant acid phosphatase-5b, Dickkopf-1, fibroblast growth factor, and sclerostin. Rates of detection of osteoporosis by DXA and QCT were compared. Correlations were calculated between baseline biochemical parameters and BMD at baseline and changes over 1 year. Multivariable regression was performed to adjust for age, sex, body mass index, and race.Results Eighty-one patients completed the study (mean age=52.6612.3 years, 56% men, 53% African American, and median dialysis vintage=41 months). At baseline, QCT and DXA of the spine identified similar rates of osteoporosis (13.6% and 13.6%), but at the hip, DXA identified more osteoporosis (22.2% versus 13.6%). At any site and by either method, 33.3% of the patients were osteoporotic. Baseline BMD correlated with sclerostin, intact parathyroid hormone, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase-5b, and fibroblast growth factor. At 1 year, hip QCT identified a higher number of patients experiencing bone loss (51.3%) than DXA (38.5%). After multivariable adjustment, baseline sclerostin and tartrate-resistant acid phosphatase-5b predicted bone loss measured by QCT of the hip; procollagen type 1 N-terminal propeptide predicted cortical spine bone gain by QCT.Conclusions QCT identified prospectively more bone loss at the hip than DXA. The baseline serum biochemical parameters sclerostin and tartrate-resistant acid phosphatase-5b were noninvasive independent predictors of bone loss in CKD patients on dialysis.

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Section: Discussionsupporting

confidence: 53%

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Malluche¹,

Davenport

Cantor³

et al. 2014

Clinical Journal of the American Society of Nephrology

122

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“…17 According to the study of Pelletier et al, serum sclerostin variability in CKD patients was explained by GFR, sex, and serum phosphate activity in multiple regression analysis. 16 These results suggest that serum phosphate may stimulate sclerostin synthesis by osteocytes, but does not uncover the potential mechanism hiding beneath and does not explain previously observed inverse relation with iPTH. 16,17 …”

Section: Sclerostin In Chronic Kidney Diseasecontrasting

confidence: 58%

“…16 These results suggest that serum phosphate may stimulate sclerostin synthesis by osteocytes, but does not uncover the potential mechanism hiding beneath and does not explain previously observed inverse relation with iPTH. 16,17 …”

Section: Sclerostin In Chronic Kidney Diseasecontrasting

confidence: 58%

“…15 Serum proteins, sclerostin and Dickkopf-1 (Dkk-1), act as soluble inhibitors of the canonical Wnt signaling pathway, which has recently been identified as the signaling pathway in PTH transduction. 16 The canonical Wnt signaling path includes the formation of complexes of Wnt with frizzled receptors, as well as with co-receptor LRP5/6, resulting in the accumulation of cytoplasmic β-catenin and its translocation to the nucleus. 17 The interaction of inhibitors (e.g., sclerostin) on the frizzled-glomerulus receptor and co-receptor LRP5/6, which binds to the Wnt protein signal, determines whether intracellular concentration of β-catenin will be high enough in the cell nucleus to cause a biological effect (stimulation of osteogenesis).…”

Section: The Role Of Sclerostin In the Regulation Of Bone Turnovermentioning

confidence: 99%

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Sclerostin: Intracellular mechanisms of action and its role in the pathogenesis of skeletal and vascular disorders

Pietrzyk¹,

Smertka²,

Chudek³

2017

Adv Clin Exp Med

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Sclerostin is a glycoprotein involved in the regulation of bone metabolism, exclusively secreted by osteocytes. It affects the activity of bone morphogenetic proteins (BMPs) and is an inhibitor of the Wnt/β-catenin metabolic pathway in bone cells. Osteocytes reduce the release of sclerostin in response to mechanical stimuli acting on bone, and thus promote the activation of osteogenic pathway Wnt/β-catenin in osteoblasts. This signaling pathway plays a key role in osteogenesis and bone turnover. Loss of sclerostin gene function is related to 3 different craniotubular hyperostosis processes: sclerosteosis, craniodiaphyseal dysplasia, and van Buchem disease. Additionally, experimental and clinical studies suggest that sclerostin may promote vascular calcification. Antibodies directed against sclerostin stimulate bone formation and represent a new therapeutic option in the treatment of diseases with increased bone resorption, such as osteoporosis and inflammatory diseases where there is generalized bone loss, periarticular osteoporosis, and cartilage damage, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and glucocorticoid-induced osteoporosis (GIO). Antibody use has the potential to offer new therapeutic approaches in the therapy of mineral and bone disorders resulting from chronic kidney disease (CKD-MBD) and vascular calcifications.

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“…Sclerostin is an antianabolic bone factor released by osteocytes. This marker increases with declining renal function and is elevated in haemodialysis patients [63,64]. It may be also associated with vasculitis and vascular calcification [65].…”

Section: Supar and Cardiovascular Diseases In Patients With Chronic Kmentioning

confidence: 99%

The role of suPAR in kidney diseases

Łącka-Gaździk

Śnit

Żak-Lenart

et al. 2017

Ann. Acad. Med. Siles.

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Przewlekła choroba nerek (PChN) to niewątpliwie problem o znaczeniu społecznym, dotyczy bowiem około 10% populacji. Poszukiwane są biomarkery, dzięki którym spośród tak dużej liczby pacjentów udałoby się wyselekcjonować osoby z dużym ryzykiem progresji choroby i jej powikłań. Główną przyczyną zgonów u pacjentów ze schyłkową niewydolnością nerek są choroby układu sercowo-naczyniowego. Przyspieszony rozwój miażdżycy w tej grupie chorych wiąże się z przewlekłym stanem zapalnym. Przedmiotem zainteresowania autorów pracy jest nowy biomarker stanu zapalnego suPAR (soluble urokinase-type plazminogen activator receptor – rozpuszczalna forma receptora aktywatora plazminogenu typu urokinazy). Z klinicznego punktu widzenia interesujący jest również związek suPAR z zakażeniami układu moczowego oraz ogniskowym segmentalnym stwardnieniem kłębuszków nerkowych (focal segmental glomerulosclerosis – FSGS). Identyfikacja suPAR, jako krążącego we krwi czynnika wywołującego FSGS, rzuca nowe światło na patomechanizm choroby i stwarza obiecujące możliwości lecznicze. Lepsze zrozumienie patogenezy omawianych schorzeń pomogłoby zredukować nieakceptowalnie wysoką śmiertelność pacjentów z PChN. Na dzień dzisiejszy nie można zlecać powszechnego oznaczania suPAR w kontekście omawianych zagadnień. Niemniej trwają badania, które pozwolą wyjaśnić niejasne kwestie dotyczące związku biomarkera z omawianymi schorzeniami nerek. Być może na podstawie ich wyników w najbliższych latach oznaczanie suPAR w wybranych chorobach nerek będzie rutynowe.

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The Relation between Renal Function and Serum Sclerostin in Adult Patients with CKD

Cited by 184 publications

References 22 publications

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Sclerostin: Intracellular mechanisms of action and its role in the pathogenesis of skeletal and vascular disorders

The role of suPAR in kidney diseases

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