Abstract
Background
Sclerostin is an osteocyte-derived inhibitor of the Wnt pathway and has been shown to play a key role in chronic kidney disease-mineral and bone disorder (CKD-MBD). The present study aimed to validate its potential as a predictor of vascular calcification in patients with CKD stages 3–4.
Methods
A total of 97 patients with CKD stages 3–4 were enrolled in this cross-sectional study. Routine clinical biochemistry tests and assays for sclerostin and mineral metabolism markers were performed. Additionally, vascular calcification was assessed by multislice spiral computed tomography. Logistic regression analyses were used to study the relationships between sclerostin and vascular calcification.
Results
Serum sclerostin levels (30.8 ± 6.4 vs. 41.7 ± 12.6 pmol/L, P < 0.05) were significantly elevated in patients with CKD stage 3a compared to in controls and increased with the decline in glomerular filtration rates. Furthermore, patients with vascular calcification had higher serum sclerostin levels. Patients with sclerostin levels above the median value had increased the prevalence of vascular calcification. Multivariate analysis revealed that sclerostin levels were positively associated with vascular calcification.
Conclusion
Our data indicate that sclerostin levels are elevated in patients with CKD and are associated with vascular calcification. Therefore, sclerostin may be used as a predictor of vascular calcification in the clinical setting.
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Abbreviations
- CKD:
-
Chronic kidney disease
- CVD:
-
Cardiovascular disease
- CKD-MBD:
-
Chronic kidney disease-mineral bone disorder
- ALP:
-
Alkaline phosphatase
- PTH:
-
Parathyroid hormone
- FGF23:
-
Fibroblast growth factor-23
- KDIGO:
-
Kidney Disease: Improving Global Outcomes
- eGFR:
-
Estimated glomerular filtration rates
- MDRD:
-
Modification of Diet in Renal Disease equation
- SCr:
-
Creatinine
- CRP:
-
C-reactive protein
- iPTH:
-
Intact PTH
- ECLIA:
-
Electrochemiluminescence immunoassay
- ELISA:
-
Enzyme-linked immunosorbent assay
- CVs:
-
Coefficients of variation
- CT:
-
Nonenhanced computed tomography
- SEM:
-
Standard error of the mean
- BMI:
-
Body mass index
- HDL:
-
High-density lipoprotein
- LDL:
-
Low-density lipoprotein
- ND-CKD:
-
Nondialysis chronic kidney disease
- CAC:
-
Coronary artery calcification
- VSMCs:
-
Vascular smooth muscle cells
References
Noordzij M, Cranenburg EM, Engelsman LF, Hermans MM, Boeschoten EW, Brandenburg VM, Bos WJ, Kooman JP, Dekker FW, Ketteler M, Schurgers LJ, Krediet RT, Korevaar JC, NECOSAD Study Group (2011) Progression of aortic calcification is associated with disorders of mineral metabolism and mortality in chronic dialysis patients. Nephrol Dial Transplant 26:1662–1669
Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, Young EW, Akizawa T, Akiba T, Pisoni RL, Robinson BM, Port FK (2008) Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 52:519–530
Cunningham J, Locatelli F, Rodriguez M (2011) Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol 6:913–921
Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL (2005) Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 16:520–528
Sigrist M, Bungay P, Taal MW, McIntyre CW (2006) Vascular calcification and cardiovascular function in chronic kidney disease. Nephrol Dial Transplant 21:707–714
Sumida Y, Nakayama M, Nagata M, Nakashita S, Suehiro T, Kaizu Y, Ikeda H, Izumaru K (2010) Carotid artery calcification and atherosclerosis at the initiation of hemodialysis in patients with end-stage renal disease. Clin Nephrol 73:360–369
London GM, Guerin AP, Marchais SJ, Métivier F, Pannier B, Adda H (2003) Arterial media calcification in endstage renal diseases: impact on all cause and cardiovascular mortality. Nephrol Dial Transplant 18:1731–1740
Adeney KL, Siscovick DS, Ix JH, Seliger SL, Shlipak MG, Jenny NS, Kestenbaum BR (2009) Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol 20:381–387
Moe SM, Reslerova M, Ketteler M, O’Neill K, Duan D, Koczman J, Westenfeld R, Jahnen-Dechent W, Chen NX (2005) Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD). Kidney Int 67:2295–2304
Nakayama M, Kaizu Y, Nagata M, Ura Y, Ikeda H, Shimamoto S, Kuma K (2013) Fibroblast growth factor 23 is associated with carotid artery calcification in chronic kidney disease patients not undergoing dialysis: a cross-sectional study. BMC Nephrol 14:22
Sabbagh Y, Graciolli FG, O’Brien S, Tang W, dos Reis LM, Ryan S, Phillips L, Boulanger J, Song W, Bracken C, Liu S, Ledbetter S, Dechow P, Canziani ME, Carvalho AB, Jorgetti V, Moyses RM, Schiavi SC (2012) Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy. J Bone Miner Res 27:1757–1772
Cejka D, Marculescu R, Kozakowski N (2014) Renal elimination of sclerostin increases with declining kidney function. J Clin Endocrinol Metab 99:248–255
Moester MJ, Papapoulos SE, Löwik CW, van Bezooijen RL (2010) Sclerostin: current knowledge and future perspectives. Calcif Tissue Int 87:99–107
Brandenburg VM, Kramann R, Koos R, Krüger T, Schurgers L, Mühlenbruch G, Hübner S, Gladziwa U, Drechsler C, Ketteler M (2013) Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study. BMC Nephrol 14:219
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 130:461–470
Morena M, Jaussent I, Dupuy AM, Bargnoux AS, Kuster N, Chenine L, Leray-Moragues H, Klouche K, Vernhet H, Canaud B, Cristol JP (2015) Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis: potential partners in vascular calcifications. Nephrol Dial Transplant 30:1345–1356
Pelletier S, Dubourg L, Carlier MC, Hadj-Aissa A, Fouque D (2013) The relation between renal function and serum sclerostin in adult patients with CKD. Clin J Am Soc Nephrol 8:819–823
Moe SM, Drüeke T (2008) Improving global outcomes in mineral and bone disorders. Clin J Am Soc Nephrol 3:S127–S130
Craver L, Marco MP, Martínez I, Rue M, Borràs M, Martín ML, Sarró F, Valdivielso JM, Fernández E (2007) Mineral metabolism parameters throughout chronic kidney disease stages 1–5—achievement of K/DOQI target ranges. Nephrol Dial Transplant 22:1171–1176
Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM (2011) Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res 109:697–711
Cannata-Andia JB, Roman-Garcia P, Hruska K (2011) The connections between vascular calcification and bone health. Nephrol Dial Transplant 26:3429–3436
Thambiah S, Roplekar R, Manghat P, Fogelman I, Fraser WD, Goldsmith D, Hampson G (2012) Circulating sclerostin and Dickkopf-1 (DKK1) in predialysis chronic kidney disease (CKD): relationship with bone density and arterial stiffness. Calcif Tissue Int 90:473–480
Mödder UI, Hoey KA, Amin S, McCready LK, Achenbach SJ, Riggs BL, Melton LJ 3rd, Khosla S (2011) Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res 26:373–379
Krishnan V, Bryant HU, Macdougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202–1209
Drüeke TB, Lafage-Proust MH (2011) Sclerostin: just one more player in renal bone disease? Clin J Am Soc Nephrol 6:700–703
Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW, Reeve J (2005) Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J 19:1842–1844
Cejka D, Herberth J, Branscum AJ, Fardo DW, Monier-Faugere MC, Diarra D, Haas M, Malluche HH (2011) Sclerostin and Dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrol 6:877–882
Viaene L, Behets GJ, Claes K, Meijers B, Blocki F, Brandenburg V, Evenepoel P, D’Haese PC (2013) Sclerostin: another bone-related protein related to all-cause mortality in haemodialysis? Nephrol Dial Transplant 28:3024–3030
Morales-Santana S, García-Fontana B, García-Martín A, Rozas-Moreno P, García-Salcedo JA, Reyes-García R, Muñoz-Torres M (2013) Atherosclerotic disease in type 2 diabetes is associated with an increase in sclerostin levels. Diabetes Care 36:1667–1674
Claes KJ, Viaene L, Heye S, Meijers B, d’Haese P, Evenepoel P (2013) Sclerostin: another vascular calcification inhibitor? J Clin Endocrinol Metab 98:3221–3228
Acknowledgments
This work was funded by Promotive Research Fund for Science and Technology Development Plan Project of Yantai, Shandong Province (2016), and was supported by National Natural Science Foundation of China (81302234).
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The authors declare that they have no competing interests.
Ethical standard
This study was conducted in accordance with the Declaration of Helsinki. All of the participants provided written informed consent for the protocol, which was approved by the Ethics Committee of Yuhuangding Hospital.
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Lv, W., Guan, L., Zhang, Y. et al. Sclerostin as a new key factor in vascular calcification in chronic kidney disease stages 3 and 4. Int Urol Nephrol 48, 2043–2050 (2016). https://doi.org/10.1007/s11255-016-1379-8
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DOI: https://doi.org/10.1007/s11255-016-1379-8