Circulating Matrix Metalloproteinase Activity and Functional Capacity in Individuals Undergoing Hemodialysis: Exploratory Findings from a Resistance Training Trial

Hugo de Luca Correa , Rafael Lavarini dos Santos , Ivo Vieira Sousa de Neto , Rodrigo Vanerson Passos Neves , Thaís Amaral Ferreira Baracho , Taynah Oliveira Martins , Jéssica Mycaella da Silva Barbosa , Thaís Branquinho de Araújo , Leandro Lima Sousa , Rebecca Salomão , Rita de Cássia Marqueti , Lysleine Alves de Deus , Fernando Costa , Thiago dos Santos Rosa

Journal of Science in Sport and Exercise ›› : 1 -11.

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Journal of Science in Sport and Exercise ›› :1 -11. DOI: 10.1007/s42978-026-00399-3
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Circulating Matrix Metalloproteinase Activity and Functional Capacity in Individuals Undergoing Hemodialysis: Exploratory Findings from a Resistance Training Trial
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Abstract

Purpose

To investigate the effects of 24 weeks of resistance training (RT) on pro- and active matrix metalloproteinases (MMPs) and their association with functional performance in end-stage kidney disease (ESKD) patients undergoing hemodialysis.

Methods

Forty-two ESKD patients (mean age: 65 ± 4 years; dry body mass: 71 ± 16 kg; body mass index: 25 ± 3 kg/m2) were randomized into two groups: the control (CTL, n = 20) and RT group (n = 22). RT was comprised three times per week for 24 weeks. Plasma MMP-2 and MMP-9 activity were assessed by zymography. Functional and body-composition outcomes included handgrip strength, fat-free mass (FFM), 5-min walking test, and the Timed Up and Go (TUG) test.

Results

Using bioinformatics tools, we found that MMP-2 gene expression in PBMCs was decreased in ESKD patients undergoing hemodialysis. At post-intervention, RT displayed a higher active MMP-2 activity, while MMP-9 did not change. After baseline adjustment, the estimated effect of RT on active MMP-2 was attenuated, whereas active MMP-9 showed a lower adjusted response in the RT group. Active MMP-2 activity was positively associated with handgrip strength, FFM (P < 0.05), and negatively correlated with TUG test (P < 0.05).

Conclusion

RT improved functional outcomes and the complex effects of RT on MMPs should be thoroughly investigated in future experimental and clinical studies.

Keywords

Matrix metalloproteinases / Strength training / End-stage kidney disease / Chronic kidney disease

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Hugo de Luca Correa, Rafael Lavarini dos Santos, Ivo Vieira Sousa de Neto, Rodrigo Vanerson Passos Neves, Thaís Amaral Ferreira Baracho, Taynah Oliveira Martins, Jéssica Mycaella da Silva Barbosa, Thaís Branquinho de Araújo, Leandro Lima Sousa, Rebecca Salomão, Rita de Cássia Marqueti, Lysleine Alves de Deus, Fernando Costa, Thiago dos Santos Rosa. Circulating Matrix Metalloproteinase Activity and Functional Capacity in Individuals Undergoing Hemodialysis: Exploratory Findings from a Resistance Training Trial. Journal of Science in Sport and Exercise 1-11 DOI:10.1007/s42978-026-00399-3

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References

[1]

Thurlow JS, Joshi M, Yan G, Norris KC, Agodoa LY, Yuan CM, et al.. Global Epidemiology of End-Stage Kidney Disease and Disparities in Kidney Replacement Therapy. Am J Nephrol, 2021, 52(2): 98-107

[2]

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, 53(4): 253-63

[3]

Correa HL, Rosa TDS, Dutra MT, Sales MM, Noll M, Deus LA, et al.. Association between dynapenic abdominal obesity and inflammatory profile in diabetic older community-dwelling patients with end-stage renal disease. Exp Gerontol, 2021, 146: 111243

[4]

Bishop NC, Burton JO, Graham-Brown MPM, Stensel DJ, Viana JL, Watson EL. Exercise and chronic kidney disease: potential mechanisms underlying the physiological benefits. Nat Rev Nephrol, 2023, 19(4): 244-56

[5]

Gadelha AB, Cesari M, Correa HL, Neves RVP, Sousa CV, Deus LA, et al.. Effects of pre-dialysis resistance training on sarcopenia, inflammatory profile, and anemia biomarkers in older community-dwelling patients with chronic kidney disease: a randomized controlled trial. Int Urol Nephrol, 2021, 53(10): 2137-47

[6]

Becerra LA, Mansour SG. Exercise and Kidney Health: Core Curriculum 2026. Am J Kidney Dis, 2026, 87(2): 246-59

[7]

de Araujo TB, de Luca Correa H, de Deus LA, Neves RVP, Reis AL, Honorato FS, et al.. The effects of home-based progressive resistance training in chronic kidney disease patients. Exp Gerontol, 2023, 171: 112030

[8]

Cai X, Zeng D, Deng J. A systematic review and meta-analysis of the efficacy of aerobic exercise combined with resistance training on maintenance hemodialysis patients. Ann Palliat Med, 2022, 11(4): 1360-8

[9]

Boukadida R, Saadaoui M, Thabet N, Olfa M, Asma F, Nouir S, et al.. The effect of intradialytic resistance exercise on physical function and dialysis adequacy in patients on maintenance hemodialysis. PLoS ONE, 2026, 21(3): e0337910

[10]

Hallan SI, Ovrehus MA, Shlipak MG, Potok OA, Romundstad S, Aspvik NP, et al.. Long-Term Physical Exercise for Preventing CKD in Older Adults: A Randomized Clinical Trial. J Am Soc Nephrol, 2025, 36(7): 1352-62

[11]

Laroui A, Galarneau L, Abolghasemi A, Benachenhou S, Plantefeve R, Bouchouirab FZ, et al.. Clinical significance of matrix metalloproteinase-9 in Fragile X Syndrome. Sci Rep, 2022, 12(1): 15386

[12]

de Almeida LGN, Thode H, Eslambolchi Y, Chopra S, Young D, Gill S, et al.. Matrix Metalloproteinases: From Molecular Mechanisms to Physiology, Pathophysiology, and Pharmacology. Pharmacol Rev, 2022, 74(3): 712-68

[13]

Ma Y, Kuang Y, Bo W, Liang Q, Zhu W, Cai M, et al. Exercise training alleviates cardiac fibrosis through increasing fibroblast growth factor 21 and regulating TGF- β1-Smad2/3-MMP2/9 signaling in mice with myocardial infarction. Int J Mol Sci. 2021;22(22):12341.

[14]

Yu W, Wang Z, Li Y, Liu L, Liu J, Ding F, et al.. Effects of autophagy and endocytosis on the activity of matrix metalloproteinase–2 in human renal proximal tubular cells under hypoxia. Mol Med Rep, 2017, 15(5): 3225-30

[15]

Cheng Z, Limbu MH, Wang Z, Liu J, Liu L, Zhang X, et al. MMP-2 and 9 in chronic kidney disease. Int J Mol Sci. 2017;18(4):776.

[16]

Marson BP, Lacchini R, Belo V, Dickel S, da Costa BP, de Figueiredo CEP, et al. Matrix metalloproteinase (MMP)-2 genetic variants modify the circulating MMP-2 levels in end-stage kidney disease. Am J Nephrol. 2012;35(3):209 –15.

[17]

Pawlak K, Mysliwiec M, Pawlak D. Peripheral blood level alterations of MMP-2 and MMP-9 in patients with chronic kidney disease on conservative treatment and on hemodialysis. Clin Biochem, 2011, 44(10–11): 838-43

[18]

Taherkhani S, Sheibani M, Mohammadkhanizadeh A, Virag JAI, de Castro Braz L, Azizi Y. Metalloproteinases (MMPs) in hypertensive disorders: role, function, pharmacology, and potential strategies to mitigate pathophysiological changes. Front Pharmacol, 2025, 16: 1559288

[19]

Akinleye AA, Chapman HM, Roman RJ, Bidwell GL. 3rd. Kidney-specific delivery of a matrix metalloproteinase-2 inhibitory peptide fused to elastin-like polypeptide reduces proteinuria and renal fibrosis in a model of salt-sensitive hypertension. J Pharmacol Exp Ther, 2025, 392(12): 103556

[20]

Baudier RL, Orlandi PF, Yang W, Chen HY, Bansal N, Blackston JW, et al.. Matrix Metalloproteinase-2 and CKD Progression: The Chronic Renal Insufficiency Cohort (CRIC) Study. Kidney Med, 2024, 6(8): 100850

[21]

de Sousa Neto IV, Durigan JLQ, Carreiro de Farias Junior G, Bogni FH, Ruivo AL, de Araujo JO, et al.. Resistance Training Modulates the Matrix Metalloproteinase-2 Activity in Different Trabecular Bones in Aged Rats. Clin Interv Aging, 2021, 16: 71-81

[22]

de Sousa Neto IV, Durigan JLQ, Guzzoni V, Tibana RA, Prestes J, de Araujo HSS, et al.. Effects of Resistance Training on Matrix Metalloproteinase Activity in Skeletal Muscles and Blood Circulation During Aging. Front Physiol, 2018, 9: 190

[23]

Segura-Orti E, Johansen KL. Exercise in end-stage renal disease. Semin Dial, 2010, 23(4): 422-30

[24]

Lagally KM, Robertson RJ. Construct validity of the OMNI resistance exercise scale. J Strength Cond Res, 2006, 20(2): 252-6

[25]

Rosa TS, Neves RVP, Deus LA, Sousa CV, da Silva Aguiar S, de Souza MK, et al.. Sprint and endurance training in relation to redox balance, inflammatory status and biomarkers of aging in master athletes. Nitric Oxide, 2020, 102: 42-51

[26]

Fan WH, Karnovsky MJ. Increased MMP-2 expression in connective tissue growth factor over-expression vascular smooth muscle cells. J Biol Chem, 2002, 277(12): 9800-5

[27]

Ma X, Liu B, Jiang Z, Rao Z, Zheng L. Physical exercise: a promising treatment against organ fibrosis. Int J Mol Sci. 2025;26(1):343.

[28]

Momi S, Falcinelli E, Petito E, Ciarrocca Taranta G, Ossoli A, Gresele P. Matrix metalloproteinase-2 on activated platelets triggers endothelial PAR-1 initiating atherosclerosis. Eur Heart J, 2022, 43(6): 504-14

[29]

Ali MAM, Garcia-Vilas JA, Cromwell CR, Hubbard BP, Hendzel MJ, Schulz R. Matrix metalloproteinase-2 mediates ribosomal RNA transcription by cleaving nucleolar histones. FEBS J, 2021, 288(23): 6736-51

[30]

Zhao Z, Zhu Y, Wan D. Exercise and tissue fibrosis: recent advances in therapeutic potential and molecular mechanisms. Front Endocrinol (Lausanne), 2025, 16: 1557797

[31]

Jones SP, O’Leary N, Pena Calderin E, Singhal R, Hellmann J, de Damacena C, et al.. Exercise sensitizes the pressure diuresis response: shifting immune landscapes may underlie renal adaptations. Am J Physiol Ren Physiol, 2025, 329(3): F362-73

[32]

Hangelbroek RW, Fazelzadeh P, Tieland M, Boekschoten MV, Hooiveld GJ, van Duynhoven JP, et al.. Expression of protocadherin gamma in skeletal muscle tissue is associated with age and muscle weakness. J Cachexia Sarcopenia Muscle, 2016, 7(5): 604-14

[33]

Kanzleiter T, Rath M, Gorgens SW, Jensen J, Tangen DS, Kolnes AJ, et al.. The myokine decorin is regulated by contraction and involved in muscle hypertrophy. Biochem Biophys Res Commun, 2014, 450(2): 1089-94

[34]

Arroyo E, Umukoro PE, Burney HN, Li Y, Li X, Lane KA, et al.. Initiation of Dialysis Is Associated With Impaired Cardiovascular Functional Capacity. J Am Heart Assoc, 2022, 11(14): e025656

[35]

Sumida K, Yamagata K, Iseki K, Tsubakihara Y. Different impact of hemodialysis vintage on cause-specific mortality in long-term hemodialysis patients. Nephrol Dial Transpl, 2016, 31(2): 298-305

[36]

Rayner HC, Zepel L, Fuller DS, Morgenstern H, Karaboyas A, Culleton BF, et al.. Recovery time, quality of life, and mortality in hemodialysis patients: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis, 2014, 64(1): 86-94

[37]

Chen Y, Aratani Y, Osawa T, Fukuyama N, Tsuji C, Nakazawa H. Activation of inducible nitric oxide synthase increases MMP-2 and MMP-9 levels in ApoE-knockout mice. Tokai J Exp Clin Med, 2008, 33(1): 28-34

[38]

Novaro V, Pustovrh C, Colman-Lerner A, Radisky D, Lo Nostro F, Paz D, et al.. Nitric oxide induces gelatinase A (matrix metalloproteinase 2) during rat embryo implantation. Fertil Steril, 2002, 78(6): 1278-87

[39]

Shen D, Lin L, Su Y, Xu J, Jiang W, Zhang Z, et al.. Inhibition of matrix metalloproteinase-9 attenuates kidney fibrosis and cellular senescence in the transition from acute kidney injury to chronic kidney disease. Ren Fail, 2025, 47(1): 2499897

[40]

Li SY, Huang PH, Yang AH, Tarng DC, Yang WC, Lin CC, et al.. Matrix metalloproteinase-9 deficiency attenuates diabetic nephropathy by modulation of podocyte functions and dedifferentiation. Kidney Int, 2014, 86(2): 358-69

[41]

Kryst J, Matejko B, Czerwinska-Ledwig O, Tota L, Zuziak R, Piotrowska A. Effects of Acute Maximum-Intensity Exercise on Matrix Metalloproteinase-2, -9, and Tissue Inhibitor of Metalloproteinase-1 Levels in Adult Males with Type 1 Diabetes Mellitus Treated with Insulin Pumps. J Clin Med, 2024, 13: 23

[42]

Al-Masri S, Coelho JN, Thomas L. Molecular pathways and emerging therapeutic targets in the pathogenesis of diabetic kidney disease. Front Physiol, 2026, 17: 1747053

[43]

Shiu YT, Northrup H, Huang Y, Cho ME, Bunsawat K. Cellular and molecular mechanisms underlying hemodialysis arteriovenous fistula dysfunction and approaches to promote maturation: a vascular perspective. Am J Physiol Heart Circ Physiol, 2025, 329(1): H241-57

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Universidade Católica De Brasília

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