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Phosphate is associated with frailty in older patients with chronic kidney disease not on dialysis

  • Nephrology - Original Paper
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Abstract

Purpose

Frailty is common in older patients with chronic kidney disease (CKD) and has been considered an independent risk factor for adverse clinical outcomes in this population. CKD-associated mineral and bone metabolism (CKD-MBD) increases energy expenditure and causes malnutrition and inflammation leading to frailty. We investigated whether CKD-MBD markers and energy metabolism are associated with frailty in patients with advanced CKD on conservative management.

Methods

In this cross-sectional study, we investigated factors associated with frailty in a sample of 75 patients ≥ 65 years, with stage 4 or 5 CKD. Collected data included age, sex, body mass index, physical activity status, educational level, Charlson Comorbidity Index, and laboratory markers. Frailty was evaluated according to Fried’s classification.

Results

Frailty was observed in 51.3% and pre-frailty in 47.3%. The frail population was significantly older, with a high proportion of females, more inactive, had lower educational levels, spent a long time sitting throughout the day, and had higher phosphate and fibroblast growth factor 21 (FGF-21). In the multivariate logistic analysis age (odds ratio 1.13, p = 0.026) and phosphate (odds ratio 3.38, p = 0.021) remained independently associated with frailty.

Conclusion

Serum phosphate seems to be a toxin associated with the frailty phenotype in older patients with CKD. Whether strategies to decrease serum phosphate would reduce the risk of frailty in this population deserves further evaluation.

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Data availability

All data supporting the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Inaba M, Okuno S, Ohno Y (2021) Importance of considering malnutrition and sarcopenia in order to improve the QOL of elderly hemodialysis patients in Japan in the Era of 100-year life. Nutrients. https://doi.org/10.3390/nu13072377

    Article  PubMed  PubMed Central  Google Scholar 

  2. Dent E, Morley JE, Cruz-Jentoft AJ, Woodhouse L, Rodriguez-Manas L, Fried LP, Woo J, Aprahamian I, Sanford A, Lundy J, Landi F, Beilby J, Martin FC, Bauer JM, Ferrucci L, Merchant RA, Dong B, Arai H, Hoogendijk EO, Won CW, Abbatecola A, Cederholm T, Strandberg T, Gutierrez Robledo LM, Flicker L, Bhasin S, Aubertin-Leheudre M, Bischoff-Ferrari HA, Guralnik JM, Muscedere J, Pahor M, Ruiz J, Negm AM, Reginster JY, Waters DL, Vellas B (2019) Physical frailty: ICFSR International Clinical Practice Guidelines for Identification and Management. J Nutr Health Aging 23(9):771–787. https://doi.org/10.1007/s12603-019-1273-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Otobe Y, Rhee CM, Nguyen M, Kalantar-Zadeh K, Kopple JD (2022) Current status of the assessment of sarcopenia, frailty, physical performance and functional status in chronic kidney disease patients. Curr Opin Nephrol Hypertens 31(1):109–128. https://doi.org/10.1097/MNH.0000000000000763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wilkinson TJ, Miksza J, Zaccardi F, Lawson C, Nixon AC, Young HML, Khunti K, Smith AC (2022) Associations between frailty trajectories and cardiovascular, renal, and mortality outcomes in chronic kidney disease. J Cachexia Sarcopenia Muscle 13(5):2426–2435. https://doi.org/10.1002/jcsm.13047

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chao CT, Wang J, Huang JW, Chan DC, Chien KL (2019) Frailty predicts an increased risk of end-stage renal disease with risk competition by mortality among 165,461 diabetic kidney disease patients. Aging Dis 10(6):1270–1281. https://doi.org/10.14336/AD.2019.0216

    Article  PubMed  PubMed Central  Google Scholar 

  6. Nixon AC, Bampouras TM, Pendleton N, Woywodt A, Mitra S, Dhaygude A (2018) Frailty and chronic kidney disease: current evidence and continuing uncertainties. Clin Kidney J 11(2):236–245. https://doi.org/10.1093/ckj/sfx134

    Article  PubMed  Google Scholar 

  7. Zhang Q, Ma Y, Lin F, Zhao J, Xiong J (2020) Frailty and mortality among patients with chronic kidney disease and end-stage renal disease: a systematic review and meta-analysis. Int Urol Nephrol 52(2):363–370. https://doi.org/10.1007/s11255-019-02369-x

    Article  CAS  PubMed  Google Scholar 

  8. Wells JN, Andrus WG Jr (1969) Fate of 2-phenethylamino-1-phenylethanol,2–14C in rats. J Pharm Sci 58(12):1553–1554. https://doi.org/10.1002/jps.2600581234

    Article  CAS  PubMed  Google Scholar 

  9. Changchien CY, Lin YH, Cheng YC, Chang HH, Peng YS, Chen Y (2019) Indoxyl sulfate induces myotube atrophy by ROS-ERK and JNK-MAFbx cascades. Chem Biol Interact 304:43–51. https://doi.org/10.1016/j.cbi.2019.02.023

    Article  CAS  PubMed  Google Scholar 

  10. Chao CT, Lin SH (2021) Uremic toxins and frailty in patients with chronic kidney disease: a molecular insight. Int J Mol Sci. https://doi.org/10.3390/ijms22126270

    Article  PubMed  PubMed Central  Google Scholar 

  11. Chao CT, Yeh HY, Tsai YT, Chuang PH, Yuan TH, Huang JW, Chen HW (2019) Natural and non-natural antioxidative compounds: potential candidates for treatment of vascular calcification. Cell Death Discov 5:145. https://doi.org/10.1038/s41420-019-0225-z

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sosa P, Alcalde-Estevez E, Plaza P, Troyano N, Alonso C, Martinez-Arias L, de Melo E, Aroeira A, Rodriguez-Puyol D, Olmos G, Lopez-Ongil S, Ruiz-Torres MP (2018) Hyperphosphatemia promotes senescence of myoblasts by impairing autophagy through ilk overexpression, a possible mechanism involved in sarcopenia. Aging Dis 9(5):769–784. https://doi.org/10.14336/AD.2017.1214

    Article  PubMed  PubMed Central  Google Scholar 

  13. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, Ckd EPI (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612. https://doi.org/10.7326/0003-4819-150-9-200905050-00006

    Article  PubMed  PubMed Central  Google Scholar 

  14. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56(3):M146-156. https://doi.org/10.1093/gerona/56.3.m146

    Article  CAS  PubMed  Google Scholar 

  15. Chowdhury R, Peel NM, Krosch M, Hubbard RE (2017) Frailty and chronic kidney disease: a systematic review. Arch Gerontol Geriatr 68:135–142. https://doi.org/10.1016/j.archger.2016.10.007

    Article  PubMed  Google Scholar 

  16. Johansen KL, Chertow GM, Jin C, Kutner NG (2007) Significance of frailty among dialysis patients. J Am Soc Nephrol 18(11):2960–2967. https://doi.org/10.1681/ASN.2007020221

    Article  PubMed  Google Scholar 

  17. Wu PY, Chao CT, Chan DC, Huang JW, Hung KY (2019) Contributors, risk associates, and complications of frailty in patients with chronic kidney disease: a scoping review. Ther Adv Chronic Dis 10:2040622319880382. https://doi.org/10.1177/2040622319880382

    Article  PubMed  PubMed Central  Google Scholar 

  18. Brigola AG, Alexandre TDS, Inouye K, Yassuda MS, Pavarini SCI, Mioshi E (2019) Limited formal education is strongly associated with lower cognitive status, functional disability and frailty status in older adults. Dement Neuropsychol 13(2):216–224. https://doi.org/10.1590/1980-57642018dn13-020011

    Article  PubMed  PubMed Central  Google Scholar 

  19. Blodgett J, Theou O, Kirkland S, Andreou P, Rockwood K (2015) The association between sedentary behaviour, moderate-vigorous physical activity and frailty in NHANES cohorts. Maturitas 80(2):187–191. https://doi.org/10.1016/j.maturitas.2014.11.010

    Article  PubMed  Google Scholar 

  20. Kehler DS, Theou O (2019) The impact of physical activity and sedentary behaviors on frailty levels. Mech Ageing Dev 180:29–41. https://doi.org/10.1016/j.mad.2019.03.004

    Article  PubMed  Google Scholar 

  21. Kohara M, Masuda T, Shiizaki K, Akimoto T, Watanabe Y, Honma S, Sekiguchi C, Miyazawa Y, Kusano E, Kanda Y, Asano Y, Kuro OM, Nagata D (2017) Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease. PLoS ONE 12(6):e0178971. https://doi.org/10.1371/journal.pone.0178971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Suassuna PGA, de Paula RB, Sanders-Pinheiro H, Moe OW, Hu MC (2019) Fibroblast growth factor 21 in chronic kidney disease. J Nephrol 32(3):365–377. https://doi.org/10.1007/s40620-018-0550-y

    Article  CAS  PubMed  Google Scholar 

  23. Sun H, Sherrier M, Li H (2021) Skeletal muscle and bone - emerging targets of fibroblast growth factor-21. Front Physiol 12:625287. https://doi.org/10.3389/fphys.2021.625287

    Article  PubMed  PubMed Central  Google Scholar 

  24. Oost LJ, Kustermann M, Armani A, Blaauw B, Romanello V (2019) Fibroblast growth factor 21 controls mitophagy and muscle mass. J Cachexia Sarcopenia Muscle 10(3):630–642. https://doi.org/10.1002/jcsm.12409

    Article  PubMed  PubMed Central  Google Scholar 

  25. Veronesi F, Borsari V, Cherubini A, Fini M (2021) Association of Klotho with physical performance and frailty in middle-aged and older adults: a systematic review. Exp Gerontol 154:111518. https://doi.org/10.1016/j.exger.2021.111518

    Article  PubMed  Google Scholar 

  26. Jovanovich A, Ginsberg C, You Z, Katz R, Ambrosius WT, Berlowitz D, Cheung AK, Cho M, Lee AK, Punzi H, Rehman S, Roumie C, Supiano MA, Wright CB, Shlipak M, Ix JH, Chonchol M (2021) FGF23, Frailty, and Falls in SPRINT. J Am Geriatr Soc 69(2):467–473. https://doi.org/10.1111/jgs.16895

    Article  PubMed  Google Scholar 

  27. Tsai PH, Yang HC, Lin C, Sung CC, Chu P, Hsu YJ (2021) Association of serum phosphate with low handgrip strength in patients with advanced chronic kidney disease. Nutrients. https://doi.org/10.3390/nu13103605

    Article  PubMed  PubMed Central  Google Scholar 

  28. Zhang YY, Yang M, Bao JF, Gu LJ, Yu HL, Yuan WJ (2018) Phosphate stimulates myotube atrophy through autophagy activation: evidence of hyperphosphatemia contributing to skeletal muscle wasting in chronic kidney disease. BMC Nephrol 19(1):45. https://doi.org/10.1186/s12882-018-0836-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sundberg CW, Prost RW, Fitts RH, Hunter SK (2019) Bioenergetic basis for the increased fatigability with ageing. J Physiol 597(19):4943–4957. https://doi.org/10.1113/JP277803

    Article  CAS  PubMed  Google Scholar 

  30. Alcalde-Estevez E, Sosa P, Asenjo-Bueno A, Plaza P, Valenzuela PL, Naves-Diaz M, Olmos G, Lopez-Ongil S, Ruiz-Torres MP (2023) Dietary phosphate restriction prevents the appearance of sarcopenia signs in old mice. J Cachexia Sarcopenia Muscle 14(2):1060–1074. https://doi.org/10.1002/jcsm.13194

    Article  PubMed  PubMed Central  Google Scholar 

  31. Improving Global Outcomes CKDMBDUWG (2017) KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 7(1):1–59. https://doi.org/10.1016/j.kisu.2017.04.001

    Article  Google Scholar 

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Acknowledgements

The authors thank all patients for their participation in the trial.

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Author information

Authors and Affiliations

  1. Department of Medicine. Nephrology Service. Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo., São Paulo, Brazil

    Mariana P. Veloso, Rosa M. A. Moyses & Rosilene M. Elias

  2. Department of Medicine. Geriatric Division. Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo, São Paulo, Brazil

    Venceslau A. Coelho

  3. Department of Health Evidence and Impact, McMaster University, Hamilton, Canada

    Nigar Sekercioglu

  4. Department of Medicine, Division of Nephrology, Health Sciences University, Istanbul, Turkey

    Nigar Sekercioglu

  5. Universidade Nove de Julho. UNINOVE, São Paulo, Brazil

    Rosilene M. Elias

Authors
  1. Mariana P. Veloso
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  2. Venceslau A. Coelho
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  3. Nigar Sekercioglu
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  4. Rosa M. A. Moyses
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Contributions

All authors equally contributed to the study’s conception and design. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rosilene M. Elias.

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Conflict of interest

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Dr. Moysés and Dr. Elias are supported by CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), though this financial support had no role in writing this paper.

Ethical approval

This study was approved by the Ethics Committee of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (#80761617.9.0000.0068).

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Veloso, M.P., Coelho, V.A., Sekercioglu, N. et al. Phosphate is associated with frailty in older patients with chronic kidney disease not on dialysis. Int Urol Nephrol (2024). https://doi.org/10.1007/s11255-024-03985-y

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