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The prevalence and potential aetiological factors associated with restless legs syndrome in patients with chronic kidney disease: a cross-sectional study

  • Nephrology - Original Paper
  • Published:
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Abstract

Background

There is limited understanding of aetiological factors of and treatment options for restless leg syndrome (RLS) in patients with chronic kidney disease (CKD). This study aimed to estimate the prevalence of RLS in CKD patients and identify factors that may contribute to RLS.

Methods

A questionnaire-based cross-sectional study of patients with CKD stage 4 (CKD 4), pre-dialysis stage 5 (CKD-5ND) and haemodialysis-dependent stage 5 (CKD-5D) was conducted. Eligible patients were enrolled from the local dialysis units and renal clinics. The International RLS Study Group rating scale was used to establish the diagnosis of RLS and quantify its severity.

Results

212 patients with CKD 4 (n = 92), CKD-5ND (n = 14) and CKD-5D (n = 106) were included. The overall prevalence of RLS was 32.1%. Women had a significantly higher odds of having RLS despite adjustment for age, diabetes, cardiovascular disease and whether patients were on dialysis (odds ratio 2.8 [95% confidence intervals 1.5–5.2]). In pre-dialysis groups, patients with RLS had significantly higher serum ferritin (323.9 [SD 338.1] vs 177.5 [SD 178.5] µg/L, p = 0.020) compared to non-RLS patients. In dialysis patients (CKD-5D), those with RLS had significantly higher total white cell (8.0 [SD 3.5] vs 6.8 [SD 1.9] × 109/L, p = 0.026) and neutrophil (6.4 [SD 3.9] vs 4.6 [SD1.7] × 109/L, p = 0.002) counts compared to patients without RLS.

Conclusion

RLS remains a significant problem in patients with CKD and may be related to underlying inflammation. Targeting this pathway may be useful. Prevalence of RLS, diagnosed using validated measures, is higher than previous reports.

Trial registration

N/A (the current study is not a trial).

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Availability of data and material

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BMI:

Body mass index

BP:

Blood pressure

CI:

Confidence interval

CKD:

Chronic kidney disease

CKD-EPI:

Chronic Kidney Disease Epidemiology Collaboration

CKD-5ND:

Chronic Kidney Disease stage 5 non-dialysis-dependent

CKD-5D:

Chronic Kidney Disease stage 5 dialysis-dependent

CVD:

Cardiovascular disease

DM:

Diabetes mellitus

HD:

Haemodialysis/haemodiafiltration

IQR:

Interquartile range

IRLSSG:

International Restless Legs Syndrome Study Group

NICE:

National Institute of Health and Care Excellence

RLS:

Restless leg syndrome

SD:

Standard deviation

UK:

United Kingdom

USA:

United States of America

References

  1. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J et al (2003) Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 4:101–119

    Article  Google Scholar 

  2. Kennedy C, Ryan SA, Kane T, Costello RW, Conlon PJ (2018) The impact of change of renal replacement therapy modality on sleep quality in patients with end-stage renal disease: a systematic review and meta-analysis. J Nephrol 31:61–70

    Article  CAS  Google Scholar 

  3. Sinclair PM (2018) Interventions for chronic kidney disease-associated restless legs syndrome. Int J Evid Based Healthc 16:182–184

    Article  Google Scholar 

  4. Novak M, Winkelman JW, Unruh M (2015) restless legs syndrome in patients with chronic kidney disease. Semin Nephrol 35:347–358

    Article  Google Scholar 

  5. Mucsi I, Molnar MZ, Ambrus C, Szeifert L, Kovacs AZ, Zoller R et al (2005) Restless legs syndrome, insomnia and quality of life in patients on maintenance dialysis. Nephrol Dial Transplant 20:571–577

    Article  Google Scholar 

  6. DeFerio JJ, Govindarajulu U, Brar A, Cukor D, Lee KG, Salifu MO (2017) Association of restless legs syndrome and mortality in end-stage renal disease: an analysis of the United States Renal Data System (USRDS). BMC Nephrol 18:258

    Article  Google Scholar 

  7. Molnar MZ, Lu JL, Kalantar-Zadeh K, Kovesdy CP (2016) Association of incident restless legs syndrome with outcomes in a large cohort of US veterans. J Sleep Res 25:47–56

    Article  Google Scholar 

  8. Winkelman JW, Chertow GM, Lazarus JM (1996) Restless legs syndrome in end-stage renal disease. Am J Kidney Dis 28:372–378

    Article  CAS  Google Scholar 

  9. Zhang J, Wang C, Gong W, Peng H, Tang Y, Li CC et al (2014) Association between sleep quality and cardiovascular damage in pre-dialysis patients with chronic kidney disease. BMC Nephrol 15:131

    Article  Google Scholar 

  10. Pierratos A, Hanly PJ (2011) Sleep disorders over the full range of chronic kidney disease. Blood Purif 31:146–150

    Article  Google Scholar 

  11. Anand S, Johansen KL, Grimes B, Kaysen GA, Dalrymple LS, Kutner NG et al (2013) Physical activity and self-reported symptoms of insomnia, restless legs syndrome, and depression: the comprehensive dialysis study. Hemodial Int 17:50–58

    Article  Google Scholar 

  12. Giannaki CD, Sakkas GK, Karatzaferi C, Hadjigeorgiou GM, Lavdas E, Liakopoulos V et al (2011) Evidence of increased muscle atrophy and impaired quality of life parameters in patients with uremic restless legs syndrome. PLoS ONE 6:e25180

    Article  CAS  Google Scholar 

  13. Mao S, Shen H, Huang S, Zhang A (2014) Restless legs syndrome in dialysis patients: a meta-analysis. Sleep Med 15:1532–1538

    Article  Google Scholar 

  14. Neves PD, Graciolli FG, Oliveira IB, Bridi RA, Moyses RM, Elias RM (2017) Effect of mineral and bone metabolism on restless legs syndrome in hemodialysis patients. J Clin Sleep Med 13:89–94

    Article  Google Scholar 

  15. Zadeh Saraji N, Hami M, Boostani R, Mojahedi MJ (2017) Restless leg syndrome in chronic hemodialysis patients in Mashhad hemodialysis centers. J Renal Inj Prev 6:137–141

    Article  Google Scholar 

  16. Gigli GL, Adorati M, Dolso P, Piani A, Valente M, Brotini S et al (2004) Restless legs syndrome in end-stage renal disease. Sleep Med 5:309–315

    Article  Google Scholar 

  17. Kim JM, Kwon HM, Lim CS, Kim YS, Lee SJ, Nam H (2008) Restless legs syndrome in patients on hemodialysis: symptom severity and risk factors. J Clin Neurol 4:153–157

    Article  Google Scholar 

  18. Murtagh FE, Addington-Hall J, Higginson IJ (2007) The prevalence of symptoms in end-stage renal disease: a systematic review. Adv Chronic Kidney Dis 14:82–99

    Article  Google Scholar 

  19. Hazara AM, Bhandari S (2019) Can incremental haemodialysis reduce early mortality rates in patients starting maintenance haemodialysis? Curr Opin Nephrol Hypertens 28:641–647

    Article  Google Scholar 

  20. Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP et al (2003) Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 4:121–132

    Article  Google Scholar 

  21. NICE Guideline (2018) Chronic kidney disease in adults: assessment and management (CG182). National Institute of Health and Care Excellence, London (Online)

    Google Scholar 

  22. Lin Z, Zhao C, Luo Q, Xia X, Yu X, Huang F (2016) Prevalence of restless legs syndrome in chronic kidney disease: a systematic review and meta-analysis of observational studies. Ren Fail 38:1335–1346

    Article  Google Scholar 

  23. Kutner NG, Bliwise DL (2002) Restless legs complaint in African–American and Caucasian hemodialysis patients. Sleep Med 3:497–500

    Article  Google Scholar 

  24. Stefanidis I, Vainas A, Dardiotis E, Giannaki CD, Gourli P, Papadopoulou D et al (2013) Restless legs syndrome in hemodialysis patients: an epidemiologic survey in Greece. Sleep Med 14:1381–1386

    Article  CAS  Google Scholar 

  25. Lin XW, Zhang JF, Qiu MY, Ni LY, Yu HL, Kuo SH et al (2019) Restless legs syndrome in end stage renal disease patients undergoing hemodialysis. BMC Neurol 19:47

    Article  Google Scholar 

  26. Rohani M, Aghaei M, Jenabi A, Yazdanfar S, Mousavi D, Miri S (2015) Restless legs syndrome in hemodialysis patients in Iran. Neurol Sci 36:723–727

    Article  Google Scholar 

  27. Weinstock LB, Walters AS, Paueksakon P (2012) Restless legs syndrome—theoretical roles of inflammatory and immune mechanisms. Sleep Med Rev 16:341–354

    Article  Google Scholar 

  28. Nuhu F, Bhandari S (2018) Oxidative stress and cardiovascular complications in chronic kidney disease, the impact of anaemia. Pharmaceuticals (Basel) 11:103

    Article  CAS  Google Scholar 

  29. La Manna G, Pizza F, Persici E, Baraldi O, Comai G, Cappuccilli ML et al (2011) Restless legs syndrome enhances cardiovascular risk and mortality in patients with end-stage kidney disease undergoing long-term haemodialysis treatment. Nephrol Dial Transplant 26:1976–1983

    Article  Google Scholar 

  30. Seeman MV (2020) Why are women prone to restless legs syndrome? Int J Environ Res Public Health 17:368

    Article  Google Scholar 

  31. Trenkwalder C, Allen R, Hogl B, Paulus W, Winkelmann J (2016) Restless legs syndrome associated with major diseases: a systematic review and new concept. Neurology 86:1336–1343

    Article  CAS  Google Scholar 

  32. Hazara AM, Bhandari S (2015) Intravenous iron administration is associated with reduced platelet counts in patients with chronic kidney disease. J Clin Pharm Ther 40:20–23

    Article  CAS  Google Scholar 

  33. Gopaluni S, Sherif M, Ahmadouk NA (2016) Interventions for chronic kidney disease-associated restless legs syndrome. Cochrane Database Syst Rev 11:CD010690

    PubMed  Google Scholar 

  34. Happe S, Sauter C, Klosch G, Saletu B, Zeitlhofer J (2003) Gabapentin versus ropinirole in the treatment of idiopathic restless legs syndrome. Neuropsychobiology 48:82–86

    Article  CAS  Google Scholar 

  35. Oertel W, Trenkwalder C, Benes H, Ferini-Strambi L, Hogl B, Poewe W et al (2011) Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study. Lancet Neurol 10:710–720

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Mr. Archie Lamplugh and Ms. Tracy Cathcart for their help with data collection during this study.

Funding

None.

Author information

Authors and Affiliations

  1. Cardiology Department, Calderdale and Huddersfield NHS Foundation Trust, Salterhebble, Halifax, HX3 0PW, West Yorkshire, UK

    Aleksandra Brzuszek

  2. Department of Nephrology and Transplant Medicine, Hull Royal Infirmary, Hull University Teaching Hospitals NHS Trust, Anlaby Road, Hull, HU3 2JZ, UK

    Adil M. Hazara & Sunil Bhandari

  3. Hull York Medical School, Hull, UK

    Adil M. Hazara & Sunil Bhandari

Authors
  1. Aleksandra Brzuszek
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  2. Adil M. Hazara
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  3. Sunil Bhandari
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Contributions

AB and SB conceived the study. AB and AMH, conducted the analysis and wrote the first draft. AMH and SB completed the final draft. All authors approve the final draft.

Corresponding author

Correspondence to Sunil Bhandari.

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Conflict of interest

The authors declare that they have no competing interests. The results presented in this paper have not been published previously in whole or part, except in abstract format.

Ethics approval and consent to participate

The study received favourable ethical approval from the South Central—Oxford C Research Ethics Committee reference 18/SC/0476; and IRAS Reference 251719.

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Not applicable.

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Brzuszek, A., Hazara, A.M. & Bhandari, S. The prevalence and potential aetiological factors associated with restless legs syndrome in patients with chronic kidney disease: a cross-sectional study. Int Urol Nephrol 54, 2599–2607 (2022). https://doi.org/10.1007/s11255-022-03166-9

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