Serum sclerostin is an independent predictor of mortality in hemodialysis patients

BMC Nephrology

Rosa MA Moysés¹  Vanda Jorgetti²  Rodrigo B Oliveira²  Fernando Godinho Zampieri³  Fabiana G Graciolli²  Luciene M dos Reis²  Rosilene M Elias²  Flávia Letícia Carvalho Gonçalves² 

[1] Universidade Nove de Julho (UNINOVE), Rua Iperoig, 690 ap 121 – Perdizes, São Paulo 05016-000, SP, Brazil;Nephrology Division, Universidade de São Paulo, São Paulo, Brazil;Emergency Medicine Division, Universidade de São Paulo, São Paulo, Brazil

关键词: Mortality risk;    Hemodialysis;    CKD-MBD;    Chronic renal failure;    Sclerostin;   

Others  :  1082546
DOI  :  10.1186/1471-2369-15-190

 received in 2014-08-13, accepted in 2014-11-27,  发布年份 2014

【 摘 要 】

Background

Sclerostin (Scl) has recently emerged as a novel marker of bone remodeling and vascular calcification. However, whether high circulating Scl is also a risk factor for death is not well established. The purpose of this study was to test whether serum Scl would be associated with mortality.

Methods

we measured serum Scl in a hemodialysis patients’ cohort, which was followed during a ten-year period. Competing risk regression models were applied, as during the follow-up, patients were exposed to both events kidney transplant and death.

Results

Ninety-one patients aged 42.3 ± 18.8 years (55% of male gender, 15% of diabetes) were included. During the follow-up, 32 patients underwent kidney transplant and 26 patients died. Non-survivals presented higher FGF23, higher Scl and lower creatinine. There was an association between all-cause mortality and higher Scl (HR = 2.2), higher age (HR = 1.04) and presence of diabetes (HR = 2.27), by competing risk analyses. Even including potential markers of mortality, as creatinine, FGF 23, and gender, Scl, age and diabetes remained significantly related to higher mortality.

Conclusion

Serum Scl is an independent predictor of mortality in dialysis patients. However, whether clinical interventions to modulate Scl would be able to improve these patients survival needs to be determined.

【 授权许可】

   
2014 Gonçalves et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G, Kidney Disease: Improving Global Outcomes (KDIGO): Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006, 69(11):1945-1953.
• [2]Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM: Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004, 15(8):2208-2218.
• [3]Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, Young EW, Akizawa T, Akiba T, Pisoni RL, Robinson BM, Port FK: 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 2008, 52(3):519-530.
• [4]Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M, Wolf M: Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008, 359(6):584-592.
• [5]Bonewald LF: The amazing osteocyte. J Bone Miner Res 2011, 26(2):229-238.
• [6]Wesseling-Perry K, Juppner H: The osteocyte in CKD: new concepts regarding the role of FGF23 in mineral metabolism and systemic complications. Bone 2013, 54(2):222-229.
• [7]Cejka D, Herberth J, Branscum AJ, Fardo DW, Monier-Faugere MC, Diarra D, Haas M, Malluche HH: Sclerostin and Dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrol 2011, 6(4):877-882.
• [8]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: Repression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy. J Bone Miner Res 2012, 27(8):1757-1772.
• [9]Viaene L, Behets GJ, Claes K, Meijers B, Blocki F, Brandenburg V, Evenepoel P, D’Haese PC: Sclerostin: another bone-related protein related to all-cause mortality in haemodialysis? Nephrol Dial Transplant 2013, 28(12):3024-3030.
• [10]Gooi JH, Pompolo S, Karsdal MA, Kulkarni NH, Kalajzic I, McAhren SH, Han B, Onyia JE, Ho PW, Gillespie MT, Walsh NC, Chia LY, Quinn JM, Martin TJ, Sims NA: Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes. Bone 2010, 46(6):1486-1497.
• [11]Klein JP, Rizzo JD, Zhang MJ, Keiding N: Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part I: unadjusted analysis. Bone Marrow Transplant 2001, 28(10):909-915.
• [12]Klein JP, Rizzo JD, Zhang MJ, Keiding N: Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part 2: Regression modeling. Bone Marrow Transplant 2001, 28(11):1001-1011.
• [13]Scrucca L, Santucci A, Aversa F: Regression modeling of competing risk using R: an in depth guide for clinicians. Bone Marrow Transplant 2010, 45(9):1388-1395.
• [14]Fine JPG, Gray RJ: A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999, 94:496-509.
• [15]Kidney Disease: Improving Global Outcomes CKDMBDWG: KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 2009, 113:S1-S130.
• [16]Baron R, Kneissel M: WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 2013, 19(2):179-192.
• [17]Kramer I, Halleux C, Keller H, Pegurri M, Gooi JH, Weber PB, Feng JQ, Bonewald LF, Kneissel M: Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis. Mol Cell Biol 2010, 30(12):3071-3085.
• [18]Ferreira JC, Ferrari GO, Neves KR, Cavallari RT, Dominguez WV, Dos Reis LM, Graciolli FG, Oliveira EC, Liu S, Sabbagh Y, Jorgetti V, Schiavi S, Moysés RM: Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease - role of sclerostin? PLoS One 2013, 8(11):e79721.
• [19]Zhu D, Mackenzie NC, Millan JL, Farquharson C, MacRae VE: The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. PLoS One 2011, 6(5):e19595.
• [20]Brandenburg VM, Kramann R, Koos R, Kruger T, Schurgers L, Muhlenbruch G, Hubner S, Gladziwa U, Drechsler C, Ketteler M: Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study. BMC Nephrol 2013, 14:219. BioMed Central Full Text
• [21]Verduijn M, Grootendorst DC, Dekker FW, Jager KJ, le Cessie S: The analysis of competing events like cause-specific mortality–beware of the Kaplan-Meier method. Nephrol Dial Transplant 2011, 26(1):56-61.
• [22]Teixeira L, Rodrigues A, Carvalho MJ, Cabrita A, Mendonca D: Modelling competing risks in nephrology research: an example in peritoneal dialysis. BMC Nephrol 2013, 14(1):110. BioMed Central Full Text
• [23]Kanbay M, Wolf M, Selcoki Y, Solak Y, Ikizek M, Uysal S, Segall L, Armutcu F, Eryonucu B, Duranay M, Goldsmith D, Covic A, Goldsmith D, Covic A: Association of serum calcitonin with coronary artery disease in individuals with and without chronic kidney disease. Int Urol Nephrol 2012, 44(4):1169-1175.
• [24]de Oliveira RB, Graciolli FG, dos Reis LM, Cancela AL, Cuppari L, Canziani ME, Carvalho AB, Jorgetti V, Moyses RM: Disturbances of Wnt/beta-catenin pathway and energy metabolism in early CKD: effect of phosphate binders. Nephrol Dial Transplant 2013, 28(10):2510-2517.
• [25]Costa AG, Cremers S, Dworakowski E, Lazaretti-Castro M, Bilezikian JP: Comparison of two commercially available ELISAs for circulating sclerostin. Osteoporos Int 2014, 25(5):1547-1554.
• [26]Vittinghoff E, McCulloch CE: Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol 2007, 165(6):710-718.