Calcified Tissue International

, Volume 99, Issue 1, pp 13–22 | Cite as

Factors Associated with the Serum Myostatin Level in Patients Undergoing Peritoneal Dialysis: Potential Effects of Skeletal Muscle Mass and Vitamin D Receptor Activator Use

  • Shunsuke Yamada
  • Kazuhiko Tsuruya
  • Hisako Yoshida
  • Masanori Tokumoto
  • Kenji Ueki
  • Hiroaki Ooboshi
  • Takanari Kitazono
Original Research
First Online:
Received:
Accepted:

Abstract

Myostatin is a member of the transforming growth factor-β family, which regulates synthesis and degradation of skeletal muscle proteins and is associated with the development of sarcopenia. It is up-regulated in the skeletal muscle of chronic kidney disease patients and is considered to be involved in the development of uremic sarcopenia. However, serum myostatin levels have rarely been determined, and the relationship between serum myostatin levels with clinical and metabolic factors remains unknown. This cross-sectional study investigated the association between serum myostatin level and clinical factors in 69 outpatients undergoing peritoneal dialysis. Serum myostatin level was determined by commercially available enzyme-linked immunosorbent assay (ELISA). Univariable and multivariable analysis were conducted to determine factors associated with serum myostatin levels. The factors included age, sex, diabetes mellitus, dialysis history, body mass index, residual kidney function, peritoneal dialysate volume, serum biochemistries, and the use of vitamin D receptor activators (VDRAs). Mean serum myostatin level was 7.59 ± 3.37 ng/mL. There was no association between serum myostatin level and residual kidney function. Serum myostatin levels were significantly and positively associated with lean body mass measured by the creatinine kinetic method and negatively associated with the use of VDRAs after adjustment for potential confounding factors. Our study indicated that serum myostatin levels are associated with skeletal muscle mass and are lower in patients treated with VDRAs. Further studies are necessary to determine the significance of measuring serum myostatin level in patients undergoing peritoneal dialysis.

Keywords

Creatinine Myostatin Peritoneal dialysis Sarcopenia Skeletal muscle mass 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

We thank the investigators and the doctors of the participating dialysis centers. We thank Edanz Editing (http://www.edanzediting.co.jp/) for carefully reading and preparing our manuscript.

Compliance with Ethical Standards

Conflict of interest

Shunsuke Yamada, Kazuhiko Tsuruya, Hisako Yoshida, Masanori Tokumoto, Kenji Ueki, Hiroaki Ooboshi, and Takanari Kitazono declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

223_2016_118_MOESM1_ESM.pptx (57 kb)
Supplementary material 1 (PPTX 56 kb)
223_2016_118_MOESM2_ESM.docx (34 kb)
Supplementary material 2 (DOCX 34 kb)

References

  1. 1.
    Kalyani RR, Corriere M, Ferrucci L (2014) Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. Lancet Diabetes Endocrinol 2:819–829CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Domański M, Ciechanowski K (2012) Sarcopenia: a major challenge in elderly patients with end-stage renal disease. J Aging Res 2012:754739PubMedPubMedCentralGoogle Scholar
  3. 3.
    Fahal IH (2014) Uraemic sarcopenia: aetiology and implications. Nephrol Dial Transplant 29:1655–1665CrossRefPubMedGoogle Scholar
  4. 4.
    Wilhelm-Leen ER, Hall YN, Tamura MK, Chertow GM (2009) Frailty and chronic kidney disease: the Third National Health and Nutrition Evaluation Survey. Am J Med 122:664–671CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Pereira RA, Cordeiro AC, Avesani CM, Carrero JJ, Lindholm B, Amparo FC, Amodeo C, Cuppari L, Kamimura M (2015) Sarcopenia in chronic kidney disease on conservative therapy: prevalence and association with mortality. Nephrol Dial Transplant 30:1718–1725CrossRefPubMedGoogle Scholar
  6. 6.
    Wang XH, Mitch WE (2014) Mechanisms of muscle wasting in chronic kidney disease. Nat Rev Nephrol 10:504–516CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Wang H, Casaburi R, Taylor WE, Aboellail H, Storer TW, Kopple JD (2005) Skeletal muscle mRNA for IGF-IEa, IGF-II, and IGF-I receptor is decreased in sedentary chronic hemodialysis patients. Kidney Int 68:352–361CrossRefPubMedGoogle Scholar
  8. 8.
    Thomas SS, Mitch WE (2013) Mechanisms stimulating muscle wasting in chronic kidney disease: the roles of the ubiquitin-proteasome system and myostatin. Clin Exp Nephrol 17:174–182CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Lee SJ, McPherron AC (2001) Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci USA 98:9306–9311CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    White TA, LeBrasseur NK (2014) Myostatin and sarcopenia: opportunities and challenges—a mini-review. Gerontology 60:289–293CrossRefPubMedGoogle Scholar
  11. 11.
    Whittemore LA, Song K, Li X, Aghajanian J, Davies M, Girgenrath S, Hill JJ, Jalenak M, Kelley P, Knight A, Maylor R, O’Hara D, Pearson A, Quazi A, Ryerson S, Tan XY, Tomkinson KN, Veldman GM, Widom A, Wright JF, Wudyka S, Zhao L, Wolfman NM (2003) Inhibition of myostatin in adult mice increases skeletal muscle mass and strength. Biochem Biophys Res Commun 300:965–971CrossRefPubMedGoogle Scholar
  12. 12.
    McCroskery S, Thomas M, Maxwell L, Sharma M, Kambadur R (2003) Myostatin negatively regulates satellite cell activation and self-renewal. J Cell Biol 162:1135–1147CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Zimmers TA, Davies MV, Koniaris LG, Haynes P, Esquela AF, Tomkinson KN, McPherron AC, Wolfman NM, Lee SJ (2002) Induction of cachexia in mice by systemically administered myostatin. Science 296:1486–1488CrossRefPubMedGoogle Scholar
  14. 14.
    Lin J, Arnold HB, Della-Fera MA, Azain MJ, Hartzell DL, Baile CA (2002) Myostatin knockout in mice increases myogenesis and decreases adipogenesis. Biochem Biophys Res Commun 291:701–706CrossRefPubMedGoogle Scholar
  15. 15.
    Verzola D, Procopio V, Sofia A, Villaggio B, Tarroni A, Bonanni A, Mannucci I, De Cian F, Gianetta E, Saffioti S, Garibotto G (2011) Apoptosis and myostatin mRNA are upregulated in the skeletal muscle of patients with chronic kidney disease. Kidney Int 79:773–782CrossRefPubMedGoogle Scholar
  16. 16.
    Zhang L, Rajan V, Lin E, Hu Z, Han HQ, Zhou X, Song Y, Min H, Wang X, Du J, Mitch WE (2011) Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease. FASEB J 25:1653–1663CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Han DS, Chen YM, Lin SY, Chang HH, Huang TM, Chi YC, Yang WS (2011) Serum myostatin levels and grip strength in normal subjects and patients on maintenance haemodialysis. Clin Endocrinol (Oxf) 75:857–863CrossRefGoogle Scholar
  18. 18.
    Yamada S, Tsuruya K, Taniguchi M, Yoshida H, Tokumoto M, Hasegawa S, Tanaka S, Eriguchi M, Nakano T, Kitazono T (2014) Relationship between residual renal function and serum fibroblast growth factor 23 in patients on peritoneal dialysis. Ther Apher Dial 18:383–390CrossRefPubMedGoogle Scholar
  19. 19.
    Working Group Committee for Preparation of Guidelines for Peritoneal Dialysis, Japanese Society for Dialysis Therapy; Japanese Society for Dialysis Therapy (2010) 2009 Japanese Society for Dialysis Therapy guidelines for peritoneal dialysis. Ther Apher Dial 14:489–504CrossRefGoogle Scholar
  20. 20.
    Payne RB, Little AJ, Williams RB, Milner JR (1973) Interpretation of serum calcium in patients with abnormal serum proteins. Br Med J 15:643–646CrossRefGoogle Scholar
  21. 21.
    Kaida H, Ishibashi M, Nishida H, Baba K, Hiromatsu Y, Okuda S, Hayabuchi N (2005) Usefulness of whole PTH assay in patients with renal osteodystrophy-correlation with bone scintigraphy. Ann Nucl Med 19:179–184CrossRefPubMedGoogle Scholar
  22. 22.
    Park J, Mehrotra R, Rhee CM, Molnar MZ, Lukowsky LR, Patel SS, Nissenson AR, Kopple JD, Kovesdy CP, Kalantar-Zadeh K (2013) Serum creatinine level, a surrogate of muscle mass, predicts mortality in peritoneal dialysis patients. Nephrol Dial Transplant 28:2146–2155CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Patel SS, Molnar MZ, Tayek JA, Ix JH, Noori N, Benner D, Heymsfield S, Kopple JD, Kovesdy CP, Kalantar-Zadeh K (2013) Serum creatinine as a marker of muscle mass in chronic kidney disease: results of a cross-sectional study and review of literature. J Cachexia Sarcopenia Muscle 4:19–29CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Tzamaloukas AH, Murata GH, Piraino B, Raj DS, VanderJagt DJ, Bernardini J, Servilla KS, Sun Y, Glew RH, Oreopoulos DG (2010) Sources of variation in estimates of lean body mass by creatinine kinetics and by methods based on body water or body mass index in patients on continuous peritoneal dialysis. J Ren Nutr 20:91–100CrossRefPubMedGoogle Scholar
  25. 25.
    Bhatla B, Moore H, Emerson P, Keshaviah P, Prowant B, Nolph KD, Singh A (1995) Lean body mass estimation by creatinine kinetics, bioimpedance, and dual energy X-ray absorptiometry in patients on continuous ambulatory peritoneal dialysis. ASAIO J 41:M442–M446CrossRefPubMedGoogle Scholar
  26. 26.
    Churchill DN, Blake PG, Jindal KK, Toffelmire EB, Goldstein MB (1999) Clinical practice guidelines for initiation of dialysis: Canadian Society of Nephrology. J Am Soc Nephrol 10(13):S289–S291PubMedGoogle Scholar
  27. 27.
    Keshaviah PR, Nolph KD, Moore HL, Prowant B, Emerson PF, Meyer M, Twardowski ZJ, Khanna R, Ponferrada L, Collins A (1994) Lean body mass estimation by creatinine kinetics. J Am Soc Nephrol 4:1475–1485PubMedGoogle Scholar
  28. 28.
    Dong J, Li YJ, Lu XH, Gan HP, Zuo L, Wang HY (2008) Correlations of lean body mass with nutritional indicators and mortality in patients on peritoneal dialysis. Kidney Int 73:334–340CrossRefPubMedGoogle Scholar
  29. 29.
    Pedersen BK (2011) Muscles and their myokines. J Exp Biol 214:337–346CrossRefPubMedGoogle Scholar
  30. 30.
    Tanner SB, Harwell SA (2015) More than healthy bones: a review of vitamin D in muscle health. Ther Adv Musculoskelet Dis 7:152–159CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Garcia LA, King KK, Ferrini MG, Norris KC, Artaza JN (2011) 1, 25(OH)2 vitamin D3 stimulates myogenic differentiation by inhibiting cell proliferation and modulating the expression of promyogenic growth factors and myostatin in C2C12 skeletal muscle cells. Endocrinology 152:2976–2986CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Taskapan H, Baysal O, Karahan D, Durmus B, Altay Z, Ulutas O (2011) Vitamin D and muscle strength, functional ability and balance in peritoneal dialysis patients with vitamin D deficiency. Clin Nephrol 76:110–116CrossRefPubMedGoogle Scholar
  33. 33.
    Girgis CM, Cha KM, Houweling PJ, Rao R, Mokbel N, Lin M, Clifton-Bligh RJ, Gunton JE (2015) Vitamin D receptor ablation and vitamin D deficiency result in reduced grip strength, altered muscle fibers, and increased myostatin in mice. Calcif Tissue Int 97:602–610CrossRefPubMedGoogle Scholar
  34. 34.
    Szulc P, Schoppet M, Goettsch C, Rauner M, Dschietzig T, Chapurlat R, Hofbauer LC (2012) Endocrine and clinical correlates of myostatin serum concentration in men: the STRAMBO Study. J Clin Endocrinol Metab 97:3700–3708CrossRefPubMedGoogle Scholar
  35. 35.
    Ballak SB, Degens H, de Haan A, Jaspers RT (2014) Aging related changes in determinants of muscle force generating capacity: a comparison of muscle aging in men and male rodents. Ageing Res Rev 14:43–55CrossRefPubMedGoogle Scholar
  36. 36.
    Miljkovic N, Lim JY, Miljkovic I, Frontera WR (2015) Aging of skeletal muscle fibers. Ann Rehabil Med 39:155–162CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Yano S, Nagai A, Isomura M, Yamasaki M, Kijima T, Takeda M, Hamano T, Nabika T (2015) Relationship between blood myostatin levels and kidney function: Shimane CoHRE Study. PLoS One 10:e0141035CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    White TA, LeBrasseur NK (2014) Myostatin and sarcopenia: opportunities and challenges—a mini-review. Gerontology 60:289–293CrossRefPubMedGoogle Scholar
  39. 39.
    Bergen HR 3rd, Farr JN, Vanderboom PM, Atkinson EJ, White TA, Singh RJ, Khosla S, LeBrasseur NK (2015) Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: insights using a new mass spectrometry-based assay. Skelet Muscle 5:21CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Bellizzi V, Scalfi L, Terracciano V, De Nicola L, Minutolo R, Marra M, Guida B, Cianciaruso B, Conte G, Di Iorio BR (2006) Early changes in bioelectrical estimates of body composition in chronic kidney disease. J Am Soc Nephrol 17:1481–1487CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Shunsuke Yamada
    • 1
    • 3
  • Kazuhiko Tsuruya
    • 1
    • 2
  • Hisako Yoshida
    • 2
  • Masanori Tokumoto
    • 3
  • Kenji Ueki
    • 1
  • Hiroaki Ooboshi
    • 3
  • Takanari Kitazono
    • 1
  1. 1.Department of Medicine and Clinical Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of Internal MedicineFukuoka Dental CollegeFukuokaJapan

Personalised recommendations