Preprint has been submitted for publication in journal
Preprint / Version 2

Quality matters: chronic kidney disease progressively impacts muscle strength independently of changes in skeletal muscle mass


  • Antoine Chatrenet APCoSS – Institute of Physical Education and Sports Sciences (IFEPSA), UCO, Angers, France
  • Pierre-Yves de Müllenheim APCoSS - Institute of Physical Education and Sports Sciences (IFEPSA), UCO Angers, France.
  • Massimo Torreggiani Néphrologie et Dialyse, Centre Hospitalier Le Mans, 72037 Le Mans, France
  • Julia Nava Hernández Centro de Atención Nutricional de Fresenius Kabi México; Sociedad Mexicana de Estudios en Ciencias de la Salud S.C.
  • Rocio Urbina Arronte Centro de Atención Nutricional de Fresenius Kabi México
  • Abril Gutiérrez Espinoza Centro de Atención Nutricional de Fresenius Kabi México; Sociedad Mexicana de Estudios en Ciencias de la Salud S.C.
  • Giorgina Barbara Piccoli Néphrologie et Dialyse, Centre Hospitalier Le Mans, 72037 Le Mans, France



kidney cachexia, skeletal muscle, nutritional status, sarcopenia, muscle force, musculoskeletal health


Background. Chronic kidney disease (CKD) is commonly associated with multifactorial neuromuscular impairment. Few studies have investigated CKD-induced changes in maximal voluntary force (MVF), and even fewer have longitudinal follow-up. The aim of this study is to investigate whether CKD progression modifies the relationship between skeletal muscle mass and force and the prevalence of sarcopenia and sarcopenic obesity.

Methods. The data used were prospectively gathered during routine check-ups in a network of nutritional centres in Mexico. From a dataset of 5430 patients, we selected 1098 patients with available anthropometric, kidney function, handgrip and bioimpedance data. The relationship between appendicular skeletal mass (ASM) and MVF was investigated in the different CKD stages using mixed models, while sarcopenia and sarcopenic obesity were compared using the Chi-2 test. Longitudinal analysis, considering individuals with at least two visits (n=516), was performed via regression models using the linear slopes with time of MVF, ASM and kidney function.

Results. After normalization with ASM, MVF was higher in CKD G1-G3 compared to G4 and G5 (p≤0.001, Cohen’s d=0.270-0.576). Slopes between MVF and ASM were lower in CKD G3, G4 and G5 than in CKD G1-G2 (-1.131 [-2.067,-0.195], p=0.019; -1.728 [-2.809,-0.647], p=0.002; -1.744 [-2.876,-0.613], p=0.003, respectively). The prevalence of sarcopenia and sarcopenic obesity did not differ across CKD stages, but recovery was most commonly observed in CKD G1-G2. Longitudinal analysis showed an independent association between the slopes of MVF, kidney function and ASM. 

Conclusions. CKD negatively, progressively and independently affects the neuromuscular system, and force production is reduced for any given muscle mass as CKD progresses. While no association was found between CKD stage and prevalence of sarcopenia, recovery was more frequent in the early CKD stages. These results suggest the importance of early rehabilitation programs to improve musculoskeletal health, quality of life and survival in CKD patients.


Metrics Loading ...


Gollie JM, Patel SS, Harris-Love MO, Cohen SD, Blackman MR. Fatigability and the Role of Neuromuscular Impairments in Chronic Kidney Disease. Am J Nephrol. 2022 Mar;1–11.

Watanabe H, Enoki Y, Maruyama T. Sarcopenia in Chronic Kidney Disease: Factors, Mechanisms, and Therapeutic Interventions. Biol Pharm Bull. 2019;42(9):1437–45.

Chatrenet A, Piccoli G, Anthierens A, Torreggiani M, Audebrand JM, Morel B, et al. Neural Drive Impairment in Chronic Kidney Disease Patients Is Associated with Neuromuscular Fatigability and Fatigue. Med Sci Sports Exerc. 2023 Apr;55(4):727–39.

Chatrenet A, Piccoli G, Audebrand JM, Torreggiani M, Barbieux J, Vaillant C, et al. Analysis of the rate of force development reveals high neuromuscular fatigability in elderly patients with chronic kidney disease. J Cachexia Sarcopenia Muscle. 2023 Jul DOI: 10.1002/jcsm.13280

Kirkman DL, Bohmke N, Carbone S, Garten RS, Rodriguez-Miguelez P, Franco RL, et al. Exercise intolerance in kidney diseases: physiological contributors and therapeutic strategies. Am J Physiol Renal Physiol. 2021 Feb;320(2):F161–73.

Wilkinson TJ, Miksza J, Yates T, Lightfoot CJ, Baker LA, Watson EL, et al. Association of sarcopenia with mortality and end-stage renal disease in those with chronic kidney disease: a UK Biobank study. J Cachexia Sarcopenia Muscle. 2021 May DOI: 10.1002/jcsm.12705

Ikizler TA, Burrowes JD, Byham-Gray LD, Campbell KL, Carrero J-J, Chan W, et al. KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update. Am J Kidney Dis. 2020 Sep;76(3):S1–107.

Leal VO, Mafra D, Fouque D, Anjos LA. Use of handgrip strength in the assessment of the muscle function of chronic kidney disease patients on dialysis: a systematic review. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2011 Apr;26(4):1354–60.

Levey AS, Eckardt K-U, Dorman NM, Christiansen SL, Hoorn EJ, Ingelfinger JR, et al. Nomenclature for kidney function and disease: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference. Kidney Int. 2020 Jun;97(6):1117–29.

Adams GR, Vaziri ND. Skeletal muscle dysfunction in chronic renal failure: effects of exercise. Am J Physiol Renal Physiol. 2006 Apr;290(4):F753-761.

Nielsen VK. The peripheral nerve function in chronic renal failure. X. Decremental nerve conduction in uremia? Acta Med Scand. 1974 Aug;196(1–2):83–6.

Doshi S, Moorthi RN, Fried LF, Sarnak MJ, Satterfield S, Shlipak M, et al. Chronic kidney disease as a risk factor for peripheral nerve impairment in older adults: A longitudinal analysis of Health, Aging and Body Composition (Health ABC) study. PloS One. 2020;15(12):e0242406.

Arnold R, Pianta TJ, Issar T, Kirby A, Scales CMK, Kwai NCG, et al. Peripheral neuropathy: an important contributor to physical limitation and morbidity in stages 3 and 4 chronic kidney disease. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2022 Mar;37(4):713–9.

Heiwe S, Clyne N, Tollbäck A, Borg K. Effects of regular resistance training on muscle histopathology and morphometry in elderly patients with chronic kidney disease. Am J Phys Med Rehabil. 2005 Nov;84(11):865–74.

Avesani CM, de Abreu AM, Ribeiro HS, Brismar TB, Stenvinkel P, Sabatino A, et al. Muscle fat infiltration in chronic kidney disease: a marker related to muscle quality, muscle strength and sarcopenia. J Nephrol. 2023 Apr;36(3):895–910.

Momb BA, Patino E, Akchurin OM, Miller MS. Iron Supplementation Improves Skeletal Muscle Contractile Properties in Mice with CKD. Kidney360. 2022 May;3(5):843.

Chalupsky M, Goodson DA, Gamboa JL, Roshanravan B. New insights into muscle function in chronic kidney disease and metabolic acidosis. Curr Opin Nephrol Hypertens. 2021 May;30(3):369–76.

Moreno-González R, Cruzado JM, Corsonello A, Fabbietti P, Tap L, Mattace-Raso F, et al. Kidney function and other associated factors of sarcopenia in community-dwelling older adults: The SCOPE study. Eur J Intern Med. 2023 Dec;0(0). DOI: 10.1016/j.ejim.2023.12.002

Troutman AD, Arroyo E, Sheridan EM, D’Amico DJ, Brandt PR, Hinrichs R, et al. Skeletal muscle atrophy in clinical and preclinical models of chronic kidney disease: A systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2024 Feb;15(1):21–35.

Lin Y-L, Chen S-Y, Lai Y-H, Wang C-H, Kuo C-H, Liou H-H, et al. Serum creatinine to cystatin C ratio predicts skeletal muscle mass and strength in patients with non-dialysis chronic kidney disease. Clin Nutr Edinb Scotl. 2019 Nov DOI: 10.1016/j.clnu.2019.10.027

Zhou Y, Hellberg M, Svensson P, Höglund P, Clyne N. Sarcopenia and relationships between muscle mass, measured glomerular filtration rate and physical function in patients with chronic kidney disease stages 3-5. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2018 Feb;33(2):342–8.

Nava J, Moran S, Figueroa V, Salinas A, Lopez M, Urbina R, et al. Successful pregnancy in a CKD patient on a low-protein, supplemented diet: an opportunity to reflect on CKD and pregnancy in Mexico, an emerging country. J Nephrol. 2017 Dec;30(6):877–82.

Chew-Harris JSC, Chin PKL, Florkowski CM, George P, Endre Z. Removal of body surface area normalisation improves raw-measured glomerular filtration rate estimation by the Chronic Kidney Disease Epidemiology Collaboration equation and drug dosing in the obese. Intern Med J. 2015;45(7):766–73.

Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known. 1916. Nutr Burbank Los Angel Cty Calif. 1916;5(5):303–11; discussion 312-313.

Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan;48(1):16–31.

Donini LM, Busetto L, Bischoff SC, Cederholm T, Ballesteros-Pomar MD, Batsis JA, et al. Definition and Diagnostic Criteria for Sarcopenic Obesity: ESPEN and EASO Consensus Statement. Obes Facts. 2022 Feb;15(3):321–35.

Studenski SA, Peters KW, Alley DE, Cawthon PM, McLean RR, Harris TB, et al. The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci. 2014 May;69(5):547–58.

Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998 Apr;147(8):755–63.

Katayıfçı N, Hüzmeli İ, İriş D, Turgut FH. Impairments of functional exercise capacity, muscle strength, balance and kinesiophobia in patients with chronic kidney disease: a cross-sectional study. BMC Nephrol. 2024 Jan;25(1):19.

Leikis MJ, McKenna MJ, Petersen AC, Kent AB, Murphy KT, Leppik JA, et al. Exercise Performance Falls over Time in Patients with Chronic Kidney Disease Despite Maintenance of Hemoglobin Concentration. Clin J Am Soc Nephrol. 2006 May;1(3):488–95.

Duarte MP, Almeida LS, Neri SGR, Oliveira JS, Wilkinson TJ, Ribeiro HS, et al. Prevalence of sarcopenia in patients with chronic kidney disease: a global systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2024 Jan DOI: 10.1002/jcsm.13425

Chatzipetrou V, Bégin M-J, Hars M, Trombetti A. Sarcopenia in Chronic Kidney Disease: A Scoping Review of Prevalence, Risk Factors, Association with Outcomes, and Treatment. Calcif Tissue Int. 2022 Jan;110(1):1–31.

Ishikawa S, Naito S, Iimori S, Takahashi D, Zeniya M, Sato H, et al. Loop diuretics are associated with greater risk of sarcopenia in patients with non-dialysis-dependent chronic kidney disease. PLOS ONE. 2018 Feb;13(2):e0192990.

Vettoretti S, Caldiroli L, Armelloni S, Ferrari C, Cesari M, Messa P. Sarcopenia is Associated with Malnutrition but Not with Systemic Inflammation in Older Persons with Advanced CKD. Nutrients. 2019 Jun;11(6):1378.

Souza VA de, Oliveira D, Barbosa SR, Corrêa JO do A, Colugnati FAB, Mansur HN, et al. Sarcopenia in patients with chronic kidney disease not yet on dialysis: Analysis of the prevalence and associated factors. PLOS ONE. 2017 Apr;12(4):e0176230.

Zheng X, Ren X, Jiang M, Han L, Zhong C. Association of sarcopenia with rapid kidney function decline and chronic kidney disease in adults with normal kidney function. Br J Nutr. 2024 Mar;131(5):821–8.

Gortan Cappellari G, Guillet C, Poggiogalle E, Ballesteros Pomar MD, Batsis JA, Boirie Y, et al. Sarcopenic obesity research perspectives outlined by the sarcopenic obesity global leadership initiative (SOGLI) - Proceedings from the SOGLI consortium meeting in rome November 2022. Clin Nutr Edinb Scotl. 2023 May;42(5):687–99.

Androga L, Sharma D, Amodu A, Abramowitz MK. Sarcopenia, obesity, and mortality in US adults with and without chronic kidney disease. Kidney Int Rep. 2017 Mar;2(2):201–11.

Carrero JJ, Johansen KL, Lindholm B, Stenvinkel P, Cuppari L, Avesani CM. Screening for muscle wasting and dysfunction in patients with chronic kidney disease. Kidney Int. 2016;90(1):53–66.

Bellafronte NT, Diani LM, Vega-Piris L, Cuadrado GB, Chiarello PG. Comparison between dual-energy x-ray absorptiometry and bioelectrical impedance for body composition measurements in adults with chronic kidney disease: A cross-sectional, longitudinal, multi-treatment analysis. Nutrition. 2021 Feb;82:111059.



2024-06-19 — Updated on 2024-06-24