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Study of serum cystatin C levels in patients with obstructive sleep apnea

Abstract

Background

Serum cystatin C is a sensitive indicator for early renal impairment in patients with obstructive sleep apnea (OSA). In patients with OSA without known chronic kidney disease (CKD), serum cystatin C was found to be elevated, indicating latent renal disease, which may be caused by recurrent episodes of hypoxemia and reoxygenation that trigger inflammatory process.

Objective

To evaluate serum levels of cystatin C in otherwise healthy patients with OSA to predict the future risk of latent renal impairment in these patients.

Patients and methods

A total of 30 patients were classified into two groups: group I included 10 healthy controls, and group II included 20 patients with OSA.

The following were done: full history taking, clinical examination, pulmonary function tests, subjective evaluation of daytime sleepiness using the Epworth Sleepiness Scale, and overnight polysomnography. Finally, serum cystatin C levels at the end of polysomnography and glomerular filtration rate was calculated using modification of diet in renal disease formula and CKD-Epidemiology Collaboration cystatin equation.

Results

In patients with OSA, the mean level of serum cystatin C was statistically significantly higher than that in controls. These higher levels were sex, age, and BMI independently. Moreover, serum levels of cystatin C in patients with OSA were significantly correlated with OSA severity (apnea-hypopnea index) and degree of nocturnal hypoxia through positive correlation with total sleep time less than 90%, total sleep time less than 80%, and respiratory disturbance index and negative correlation with average SPO2%, lowest SPO2%, and estimated glomerular filtration rate by CKD-Epidemiology Collaboration cystatin equation.

Conclusions

Higher serum levels of cystatin C were detected in patients with OSA without known comorbidities, which indicates that these patients are at a higher risk of developing CKD. Intermittent hypoxia seems to have the main role in the progression of this process.

References

  1. Banno K, Manfreda J, Walld R, Walld R, Delaive K, Kryger M. Healthcare utilization in women with obstructive sleep apnea syndrome 2 years after diagnosis and treatment. Sleep 2006; 29:1307–1311.

    Article  Google Scholar 

  2. Fleischmann G, Fillafer G, Matterer H, Skrabal F, Kotanko P. Prevalence of chronic kidney disease in patients with suspected sleep apnoea. Transplant 2010; 25:181–186.

    Google Scholar 

  3. Nicholl DDM, Ahmed SB, Loewen AHS, Hemmelgarn BR, Sola DY, Beecroft JM, et al. Declining kidney function increases the prevalence of sleep apnea and nocturnal hypoxia. Chest 2012; 141;1422–1430.

    Article  Google Scholar 

  4. Blaydon DC, Nitoiu D, Eckl KM, Cabra RM, Bland P, Hausser I, et al. Mutations in CSTA, encoding cystatin A, underlie exfoliative ichthyosis and reveal a role for this protease inhibitor in cell-cell adhesion. Am J Human Genet 2011; 89;564–571.

    Article  CAS  Google Scholar 

  5. Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 2002 40;221–226.

    Article  CAS  Google Scholar 

  6. American Academy of Sleep Medicine. International classification of sleep disorders. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014.

    Google Scholar 

  7. Johns MW. A new method for measuring daytime sleepiness: The Epworth Sleepiness Scale. Sleep 1991; 14:540–545.

    PubMed  CAS  Google Scholar 

  8. Berry RB, Brooks R, Gamaldo CE, Harding SM, Lloyd RM, Marcus CL, Vaughn BV, for the American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications, Version 2.3: American Academy of Sleep Medicine, Westchester, IL, 2016.

    Google Scholar 

  9. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003; 26:3160–3167.

    Article  Google Scholar 

  10. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150;604–612.

    Article  Google Scholar 

  11. Levey AS, Stevens LA. Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions. Am J Kidney Dis 2010; 55:622–627.

    Article  Google Scholar 

  12. Kato K, Takata Y, Usuietal Y. Severe obstructive sleep apnea increases cystatin C in clinically latent renal dysfunction. Respir Med 2011; 105:643–649.

    Article  Google Scholar 

  13. Zhang XB, Lin QC, Deng CS, Chen GP, Cai ZM, Chen H, et al. Elevated serum cystatin C in severe OSA younger men without complications. Sleep Breath 2013; 17:235–241.

    Article  CAS  Google Scholar 

  14. Archontogeorgis K, Nena E, Tsigalou C, Voulgaris A, Xanthoudaki M, Froudarakis M, et al. Cystatin C levels in middle-aged patients with obstructive sleep apnea syndrome. Pulm Med 2016; 2016:8081723.

    Article  CAS  Google Scholar 

  15. Chuang LP, Lin SW, Lee LA, Chang CH, Huang HY, Chung H. Elevated serum markers of acute kidney injury in patients with obstructive sleep apnea. J Clin Sleep Med 2019; 15:207–213.

    Article  Google Scholar 

  16. Chung L, Yan EB, You H, Wai J, Zhi Z. Preliminary study on the relationship between OSA and renal function. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2019; 33:298–303.

    Google Scholar 

  17. Beben T, Rifkin DE. GFR estimating equations and liver disease. Adv Chronic Kidney Dise 2015; 22:337–342.

    Article  Google Scholar 

  18. Chou YT, Lee PH, Yang CT, Lin CL, Veasey S, Chuang LP, et al. Obstructive sleep apnea: a stand-alone risk factor for chronic kidney disease. Nephrol Dialy Transplant 2011; 26:2244–2250.

    Article  Google Scholar 

  19. Matsushita K, Mahmoodi BK, Woodward M, Emberson JR, Jafar TH, Jee SH, et al. Chronic Kidney Disease Prognosis Consortium. Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. JAMA 2012; 307:1941–1951.

    Article  CAS  Google Scholar 

  20. Shlipak MG, Matsushita K, Ärnlöv J, Inker LA, Phil RK, Polkinghorne KR, et al. Cystatin C versus creatinine in determining risk based on kidney function. New Engl J Med 2013; 369:932–943.

    Article  CAS  Google Scholar 

  21. Rogacev KS, Pickering JW, Seiler S, Zawada AM, Emrich I, Fliser D, et al. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation incorporating both cystatin C and creatinine best predicts individual risk. Nephrol Dial Transplant 2014; 29:348–355.

    Article  CAS  Google Scholar 

  22. Zalucky AA, Nicholl DD, Hanly PJ, Poulin MJ, Turin TC, Walji S, et al. Nocturnal hypoxemia severity and renin-angiotensin system activity in obstructive sleep apnea. Am J Respir Crit Care Med 2015; 192;873–880.

    Article  CAS  Google Scholar 

  23. Doğaner YÇ, Aydoğan Ü, Rohrer JE, Aydoğdu A, Çaycı T, Barçın C, et al. Comparison of estimated GFR equations based on serum cystatin C alone and in combination with serum creatinine in patients with coronary artery disease. Anatol J Cardiol 2015; 15:571.

    Article  CAS  Google Scholar 

  24. Uyar M, Davutoğlu V, Gündoğdu N, Kosovalı D, Sarı İ. Renal functions in obstructive sleep apnea patients. Sleep Breath 2016; 20:191–195.

    Article  Google Scholar 

  25. Shardlow A, McIntyre NJ, Fraser SD, Roderick P, Raftery J, Fluck RJ, et al. The clinical utility and cost impact of cystatin C measurement in the diagnosis and management of chronic kidney disease: a primary care cohort study. PLoS Med 2017; 14:e1002400.

    Article  Google Scholar 

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Correspondence to Salwa Ganna MD.

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Elfeky, E., El-Zaher, A.A., Elbendary, A. et al. Study of serum cystatin C levels in patients with obstructive sleep apnea. Egypt J Bronchol 13, 563–569 (2019). https://doi.org/10.4103/ejb.ejb_31_19

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  • DOI: https://doi.org/10.4103/ejb.ejb_31_19

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