Beneficial Effects of Physical Exercise on the Osteo-renal Klotho-FGF-23 Axis in Chronic Kidney Disease: A Systematic Review with Meta-analysis

Overview

Journal Int J Med Sci

Specialty General Medicine

Date 2024 Jan 3

PMID 38169578

Authors

Rafael Fernandez Castillo

Raquel Garcia Perez

Antonio Linan Gonzalez

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to investigate the efficacy of physical exercise in chronic kidney disease, describing its impact on the Klotho-FGF23 axis. PubMed, Web of Science and Scopus databases, updated to January 2023, were searched. The present study employed mean difference and a 95% confidence interval (CI) to examine the efficacy of the intervention. Heterogeneity was assessed through inconsistency statistics (I2). Out of the 299 studies identified, a total of 4 randomized controlled trials (RCTs), comprising 272 participants, met the eligibility criteria. Compared with the control group, physical exercise significantly decreased the concentrations of FGF23 (MD: -102.07 Pg/mL, 95% CI: -176.23.47, -27.91 I2= 97%, p = 0.001), and a significantly increased the concentrations of Klotho protein: (MD: 158.82 Pg/mL, 95% CI: 123.33, -194.31, I2 = 0%, p = 0.001). The results of our study indicated that the exercise has a direct relationship with Klotho-FGF23 axis. We can conclude that physical exercise in patients with CKD produces beneficial effects on the pathophysiological components related to this disease, including cardiorespiratory fitness and vascular functions. As observed, both endurance and aerobic physical exercise increase Klotho production and decrease FGF23 levels. Evidence indicates that exercise attenuates the progression of CKD, improves uremic parameters and down-regulates inflammation-related markers.

Citing Articles

Skeletal Muscle Injury in Chronic Kidney Disease-From Histologic Changes to Molecular Mechanisms and to Novel Therapies.

Heitman K, Alexander M, Faul C Int J Mol Sci. 2024; 25(10).

PMID: 38791164 PMC: 11121428. DOI: 10.3390/ijms25105117.

References

Scialla J, Wolf M . Roles of phosphate and fibroblast growth factor 23 in cardiovascular disease. Nat Rev Nephrol. 2014; 10(5):268-78. DOI: 10.1038/nrneph.2014.49. View

Shardell M, Semba R, Kalyani R, Hicks G, Bandinelli S, Ferrucci L . Serum 25-Hydroxyvitamin D, Plasma Klotho, and Lower-Extremity Physical Performance Among Older Adults: Findings From the InCHIANTI Study. J Gerontol A Biol Sci Med Sci. 2015; 70(9):1156-62. PMC: 4553717. DOI: 10.1093/gerona/glv017. View

Isakova T, Xie H, Yang W, Xie D, Anderson A, Scialla J . Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011; 305(23):2432-9. PMC: 3124770. DOI: 10.1001/jama.2011.826. View

Gutierrez O, Isakova T, Rhee E, Shah A, Holmes J, Collerone G . Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol. 2005; 16(7):2205-15. DOI: 10.1681/ASN.2005010052. View

Neves R, Correa H, Deus L, Reis A, Souza M, Simoes H . Dynamic not isometric training blunts osteo-renal disease and improves the sclerostin/FGF23/Klotho axis in maintenance hemodialysis patients: a randomized clinical trial. J Appl Physiol (1985). 2020; 130(2):508-516. DOI: 10.1152/japplphysiol.00416.2020. View

Beetham K, Howden E, Fassett R, Petersen A, Trewin A, Isbel N . High-intensity interval training in chronic kidney disease: A randomized pilot study. Scand J Med Sci Sports. 2019; 29(8):1197-1204. DOI: 10.1111/sms.13436. View

Schuler G, Adams V, Goto Y . Role of exercise in the prevention of cardiovascular disease: results, mechanisms, and new perspectives. Eur Heart J. 2013; 34(24):1790-9. DOI: 10.1093/eurheartj/eht111. View

Greenwood S, Koufaki P, Mercer T, MacLaughlin H, Rush R, Lindup H . Effect of exercise training on estimated GFR, vascular health, and cardiorespiratory fitness in patients with CKD: a pilot randomized controlled trial. Am J Kidney Dis. 2014; 65(3):425-34. DOI: 10.1053/j.ajkd.2014.07.015. View

Hu M, Shi M, Zhang J, Quinones H, Griffith C, Kuro-O M . Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2010; 22(1):124-36. PMC: 3014041. DOI: 10.1681/ASN.2009121311. View

10.

Larsson T, Nisbeth U, Ljunggren O, Juppner H, Jonsson K . Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int. 2003; 64(6):2272-9. DOI: 10.1046/j.1523-1755.2003.00328.x. View

11.

Yamamoto R, Nagasawa Y, Shoji T, Iwatani H, Hamano T, Kawada N . Cigarette smoking and progression of IgA nephropathy. Am J Kidney Dis. 2010; 56(2):313-24. DOI: 10.1053/j.ajkd.2010.02.351. View

12.

Guo C, Tam T, Bo Y, Chang L, Lao X, Neil Thomas G . Habitual physical activity, renal function and chronic kidney disease: a cohort study of nearly 200 000 adults. Br J Sports Med. 2020; 54(20):1225-1230. DOI: 10.1136/bjsports-2019-100989. View

13.

Villanego F, Naranjo J, Vigara L, Cazorla J, Montero M, Garcia T . Impact of physical exercise in patients with chronic kidney disease: Sistematic review and meta-analysis. Nefrologia (Engl Ed). 2020; 40(3):237-252. DOI: 10.1016/j.nefro.2020.01.002. View

14.

Shlipak M, Fried L, Cushman M, Manolio T, Peterson D, Stehman-Breen C . Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors. JAMA. 2005; 293(14):1737-45. DOI: 10.1001/jama.293.14.1737. View

15.

Hu M, Kuro-O M, Moe O . The emerging role of Klotho in clinical nephrology. Nephrol Dial Transplant. 2012; 27(7):2650-7. PMC: 3398064. DOI: 10.1093/ndt/gfs160. View

16.

Castillo R . Pathophysiologic Implications and Therapeutic Approach of Klotho in Chronic Kidney Disease: A Systematic Review. Lab Invest. 2023; 103(7):100178. DOI: 10.1016/j.labinv.2023.100178. View

17.

Mustata S, Chan C, Lai V, Miller J . Impact of an exercise program on arterial stiffness and insulin resistance in hemodialysis patients. J Am Soc Nephrol. 2004; 15(10):2713-8. DOI: 10.1097/01.ASN.0000140256.21892.89. View

18.

Van Craenenbroeck A, Van Craenenbroeck E, Kouidi E, Vrints C, Couttenye M, Conraads V . Vascular effects of exercise training in CKD: current evidence and pathophysiological mechanisms. Clin J Am Soc Nephrol. 2014; 9(7):1305-18. PMC: 4078973. DOI: 10.2215/CJN.13031213. View

19.

Xie J, Yoon J, An S, Kuro-O M, Huang C . Soluble Klotho Protects against Uremic Cardiomyopathy Independently of Fibroblast Growth Factor 23 and Phosphate. J Am Soc Nephrol. 2014; 26(5):1150-60. PMC: 4413766. DOI: 10.1681/ASN.2014040325. View

20.

Fliser D, Kollerits B, Neyer U, Ankerst D, Lhotta K, Lingenhel A . Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol. 2007; 18(9):2600-8. DOI: 10.1681/ASN.2006080936. View