Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Protein, malnutrition and wasting disorders

Lower thigh muscle mass is associated with all-cause and cardiovascular mortality in elderly hemodialysis patients

Abstract

Background/Objectives:

Higher body mass index appears protective in hemodialysis patients, although it remains to be determined which component of muscle or fat mass is primarily associated with this survival advantage.

Subjects/Methods:

Eighty-one hemodialysis patients in our institution were prospectively followed from July 2011 to August 2015. Muscle and fat mass were evaluated by measuring the cross-sectional areas of the thigh and abdomen using computed tomography. The relationship between muscle and fat mass, and all-cause and cardiovascular mortality was studied using the Kaplan–Meier analyses and multivariate Cox proportional hazard models.

Results:

During more than 4 years of follow-up, 26 patients (32%) died. In the Kaplan–Meier curve analyses, lower thigh muscle mass was significantly associated with all-cause and cardiovascular mortality (log-rank test, P<0.01 and P<0.001, respectively), but there was no such association with thigh fat, abdominal muscle and fat mass levels. In multivariate Cox proportional hazard models, each 0.1 cm2/kg increase in the thigh muscle area adjusted by dry weight was associated with an estimated 22% lower risk of all-cause mortality (95% confidence interval (95% CI), 0.64–0.95, P<0.05) and a 30% lower risk of cardiovascular mortality (95% CI, 0.54–0.90, P<0.01).

Conclusions:

Lower thigh muscle mass is significantly associated with all-cause and cardiovascular mortality in hemodialysis patients. Our findings indicate the importance of focusing on the muscle mass of lower extremities to predict the clinical outcomes of hemodialysis patients.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1
Figure 2

References

  1. Bergstrom J . Nutrition and mortality in hemodialysis. J Am Soc Nephrol 1995; 6: 1329–1341.

    CAS  PubMed  Google Scholar 

  2. Kopple JD, Zhu X, Lew NL, Lowrie EG . Body weight-for-height relationships predict mortality in maintenance hemodialysis patients. Kidney Int 1999; 56: 1136–1148.

    Article  CAS  Google Scholar 

  3. Degoulet P, Legrain M, Reach I, Aime F, Devries C, Rojas P et al. Mortality risk factors in patients treated by chronic hemodialysis. Report of the Diaphane collaborative study. Nephron 1982; 31: 103–110.

    Article  CAS  Google Scholar 

  4. Leavey SF, McCullough K, Hecking E, Goodkin D, Port FK, Young EW . Body mass index and mortality in 'healthier' as compared with 'sicker' haemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 2001; 16: 2386–2394.

    Article  CAS  Google Scholar 

  5. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr . Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999; 341: 1097–1105.

    Article  CAS  Google Scholar 

  6. Fleischmann EH, Bower JD, Salahudeen AK . Risk factor paradox in hemodialysis: better nutrition as a partial explanation. ASAIO J 2001; 47: 74–81.

    Article  CAS  Google Scholar 

  7. Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD . Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int 2003; 63: 793–808.

    Article  Google Scholar 

  8. Beddhu S, Pappas LM, Ramkumar N, Samore M . Effects of body size and body composition on survival in hemodialysis patients. J Am Soc Nephrol 2003; 14: 2366–2372.

    Article  Google Scholar 

  9. Caetano C, Valente A, Oliveira T, Garagarza C . Body composition and mortality predictors in hemodialysis patients. J Ren Nutr 2016; 26: 81–86.

    Article  Google Scholar 

  10. Fukasawa H, Kaneko M, Niwa H, Matsuyama T, Yasuda H, Kumagai H et al. Circulating 20 S proteasome is independently associated with abdominal muscle mass in hemodialysis patients. PLoS One 2015; 10: e0121352.

    Article  Google Scholar 

  11. Fukasawa H, Ishigaki S, Kinoshita-Katahashi N, Niwa H, Yasuda H, Kumagai H et al. Plasma levels of fibroblast growth factor-23 are associated with muscle mass in haemodialysis patients. Nephrology (Carlton) 2014; 19: 784–790.

    Article  CAS  Google Scholar 

  12. Fukasawa H, Ishigaki S, Kinoshita-Katahashi N, Yasuda H, Kumagai H, Furuya R . Plasma levels of the pro-inflammatory protein S100A12 (EN-RAGE) are associated with muscle and fat mass in hemodialysis patients: a cross-sectional study. Nutr J 2014; 13: 48.

    Article  Google Scholar 

  13. Kaizu Y, Ohkawa S, Kumagai H . Muscle mass index in haemodialysis patients: a comparison of indices obtained by routine clinical examinations. Nephrol Dial Transplant 2002; 17: 442–448.

    Article  Google Scholar 

  14. Ohkawa S, Kaizu Y, Odamaki M, Ikegaya N, Hibi I, Miyaji K et al. Optimum dietary protein requirement in nondiabetic maintenance hemodialysis patients. Am J Kidney Dis 2004; 43: 454–463.

    Article  Google Scholar 

  15. Ochi M, Kohara K, Tabara Y, Kido T, Uetani E, Ochi N et al. Arterial stiffness is associated with low thigh muscle mass in middle-aged to elderly men. Atherosclerosis 2010; 212: 327–332.

    Article  CAS  Google Scholar 

  16. KDOQI . KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Am J Kidney Dis 2007; 49: S12–154.

    Article  Google Scholar 

  17. Walther CP, Carter CW, Low CL, Williams P, Rifkin DE, Steiner RW et al. Interdialytic creatinine change versus predialysis creatinine as indicators of nutritional status in maintenance hemodialysis. Nephrol Dial Transplant 2012; 27: 771–776.

    Article  CAS  Google Scholar 

  18. Park J, Mehrotra R, Rhee CM, Molnar MZ, Lukowsky LR, Patel SS et al. Serum creatinine level, a surrogate of muscle mass, predicts mortality in peritoneal dialysis patients. Nephrol Dial Transplant 2013; 28: 2146–2155.

    Article  CAS  Google Scholar 

  19. Carrero JJ, Chmielewski M, Axelsson J, Snaedal S, Heimburger O, Barany P et al. Muscle atrophy, inflammation and clinical outcome in incident and prevalent dialysis patients. Clin Nutr 2008; 27: 557–564.

    Article  Google Scholar 

  20. Kalantar-Zadeh K, Kuwae N, Wu DY, Shantouf RS, Fouque D, Anker SD et al. Associations of body fat and its changes over time with quality of life and prospective mortality in hemodialysis patients. Am J Clin Nutr 2006; 83: 202–210.

    Article  CAS  Google Scholar 

  21. Kakiya R, Shoji T, Tsujimoto Y, Tatsumi N, Hatsuda S, Shinohara K et al. Body fat mass and lean mass as predictors of survival in hemodialysis patients. Kidney Int 2006; 70: 549–556.

    Article  CAS  Google Scholar 

  22. Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I et al. A global clinical measure of fitness and frailty in elderly people. CMAJ 2005; 173: 489–495.

    Article  Google Scholar 

  23. Wolfe RR . The underappreciated role of muscle in health and disease. Am J Clin Nutr 2006; 84: 475–482.

    Article  CAS  Google Scholar 

  24. Roshanravan B, Robinson-Cohen C, Patel KV, Ayers E, Littman AJ, de Boer IH et al. Association between physical performance and all-cause mortality in CKD. J Am Soc Nephrol 2013; 24: 822–830.

    Article  Google Scholar 

  25. Hida T, Ishiguro N, Shimokata H, Sakai Y, Matsui Y, Takemura M et al. High prevalence of sarcopenia and reduced leg muscle mass in Japanese patients immediately after a hip fracture. Geriatr Gerontol Int 2013; 13: 413–420.

    Article  Google Scholar 

  26. Isoyama N, Qureshi AR, Avesani CM, Lindholm B, Barany P, Heimburger O et al. Comparative associations of muscle mass and muscle strength with mortality in dialysis patients. Clin J Am Soc Nephrol 2014; 9: 1720–1728.

    Article  Google Scholar 

  27. Kato A, Ishida J, Endo Y, Takita T, Furuhashi M, Maruyama Y et al. Association of abdominal visceral adiposity and thigh sarcopenia with changes of arteriosclerosis in haemodialysis patients. Nephrol Dial Transplant 2011; 26: 1967–1976.

    Article  Google Scholar 

  28. Carnagarin R, Dharmarajan AM, Dass CR . Molecular aspects of glucose homeostasis in skeletal muscle - a focus on the molecular mechanisms of insulin resistance. Mol Cell Endocrinol 2015; 417: 52–62.

    Article  CAS  Google Scholar 

  29. Srikanthan P, Karlamangla AS . Relative muscle mass is inversely associated with insulin resistance and prediabetes. Findings from the third National Health and Nutrition Examination Survey. J Clin Endocrinol Metab 2011; 96: 2898–2903.

    Article  CAS  Google Scholar 

  30. Srikanthan P, Karlamangla AS . Muscle mass index as a predictor of longevity in older adults. Am J Med 2014; 127: 547–553.

    Article  Google Scholar 

  31. Koppe L, Pelletier CC, Alix PM, Kalbacher E, Fouque D, Soulage CO et al. Insulin resistance in chronic kidney disease: new lessons from experimental models. Nephrol Dial Transplant 2014; 29: 1666–1674.

    Article  CAS  Google Scholar 

  32. Mitch WE, Goldberg AL . Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med 1996; 335: 1897–1905.

    Article  CAS  Google Scholar 

  33. Fukasawa H . The role of the ubiquitin-proteasome system in kidney diseases. Clin Exp Nephrol 2012; 16: 507–517.

    Article  CAS  Google Scholar 

  34. Cheema B, Abas H, Smith B, O'Sullivan AJ, Chan M, Patwardhan A et al. Investigation of skeletal muscle quantity and quality in end-stage renal disease. Nephrology (Carlton) 2010; 15: 454–463.

    Article  CAS  Google Scholar 

  35. Tuttle LJ, Sinacore DR, Cade WT, Mueller MJ . Lower physical activity is associated with higher intermuscular adipose tissue in people with type 2 diabetes and peripheral neuropathy. Phys Ther 2011; 91: 923–930.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Dr Kazuhiro Saisu (Juzen hospital, Hamamatsu, Japan) for providing the clinical advice and information. This work was supported by grants from The Kidney Foundation, Japan (JKFB 15–19).

Author contributions

HF, HY, HK and RF designed the study. MK, HN and TM were involved in the data acquisition. HF, HK and RF carried out the statistical analysis and drafted the manuscript. All authors read, revised and approved the final version of manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H Fukasawa.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Fukasawa, H., Kaneko, M., Niwa, H. et al. Lower thigh muscle mass is associated with all-cause and cardiovascular mortality in elderly hemodialysis patients. Eur J Clin Nutr 71, 64–69 (2017). https://doi.org/10.1038/ejcn.2016.186

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2016.186

This article is cited by

Search

Quick links