Serum levels of NGAL and cystatin C as markers of early kidney dysfunction in patients with obstructive sleep apnea syndrome
- 128 Downloads
Obstructive sleep apnea syndrome (OSAS) has been recently proposed as an independent risk factor for chronic kidney disease. Cystatin C (Cyst C) and neutrophil gelatinase-associated lipocalin (NGAL) are novel biomarkers for the earlier detection of latent kidney disease. The aim of the study was to assess serum Cyst C and NGAL levels in otherwise healthy OSAS patients and to explore possible associations with sleep parameters.
Consecutive subjects (n = 96, 79.2% males), without known comorbidities, with symptoms suggestive of OSAS were included. All of them underwent polysomnography (PSG) and blood examination for the measurement of serum Cyst C and NGAL levels.
Based on apnea-hypopnea index (AHI), subjects were classified into two groups: 32 controls and 64 OSAS patients, with no significant differences in terms of age (50.1 ± 11.7 vs 51 ± 12.2 years, p = 0.747) and BMI (33.9 ± 8.8 vs 35.9 ± 13.1 kg/m2, p = 0.449). Serum Cyst C and NGAL mean levels were higher in OSAS patients compared to those in controls (1155.2 ± 319.3 vs 966.8 ± 173 ng/ml, p = 0.001, and 43.7 ± 23.2 vs 35.6 ± 13.8 ng/ml, p = 0.035, respectively). After adjustment for age and BMI in OSAS patients, serum NGAL levels were associated with AHI (β = 0.341, p = 0.015) and minimum oxyhemoglobin saturation during sleep (β = − 0.275, p = 0.032), while serum Cyst C levels were associated with percentage of time with oxyhemoglobin saturation < 90% (β = 0.270, p = 0.043), average (β = − 0.308, p = 0.018), and minimum (β = − 0.410, p = 0.001) oxyhemoglobin saturation during sleep.
Higher risk for latent kidney disease in otherwise healthy OSAS patients is indicated. Sleep hypoxia seems to be a significant contributor in the pathogenetic process of renal dysfunction in OSAS.
KeywordsCystatin C NGAL Kidney injury Kidney dysfunction Obstructive sleep apnea syndrome
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 3.Gottlieb DJ, Yenokyan G, Newman AB, O'Connor GT, Punjabi NM, Quan SF, Redline S, Resnick HE, Tong EK, Diener-West M, Shahar E (2010) Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the sleep heart health study. Circulation 122:352–360. https://doi.org/10.1161/CIRCULATIONAHA.109.901801 CrossRefGoogle Scholar
- 4.Redline S, Yenokyan G, Gottlieb DJ, Shahar E, O’Connor GT, Resnick HE, Diener-West M, Sanders MH, Wolf PA, Geraghty EM, Ali T, Lebowitz M, Punjabi NM (2010) Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study. Am J Respir Crit Care Med 182:269–277. https://doi.org/10.1164/rccm.200911-1746OC CrossRefGoogle Scholar
- 7.Molnar MZ, Mucsi I, Novak M, Szabo Z, Freire AX, Huch KM, Arah OA, Ma JZ, Lu JL, Sim JJ, Streja E, Kalantar-Zadeh K, Kovesdy CP (2015) Association of incident obstructive sleep apnoea with outcomes in a large cohort of US veterans. Thorax 70:888–895. https://doi.org/10.1136/thoraxjnl-2015-206970 CrossRefGoogle Scholar
- 8.Lee Y-C, Hung S-Y, Wang H-K, Lin CW, Wang HH, Chen SW, Chang MY, Ho LC, Chen YT, Liou HH, Tsai TC, Tseng SH, Wang WM, Lin SH, Chiou YY (2015) Sleep apnea and the risk of chronic kidney disease: a nationwide population-based cohort study. Sleep 38:213–221. https://doi.org/10.5665/sleep.4400 CrossRefGoogle Scholar
- 9.Marrone O, Battaglia S, Steiropoulos P, Basoglu OK, Kvamme JA, Ryan S, Pepin JL, Verbraecken J, Grote L, Hedner J, Bonsignore MR, the ESADA study group (2016) Chronic kidney disease in European patients with obstructive sleep apnea: the ESADA cohort study. J Sleep Res 25:739–745. https://doi.org/10.1111/jsr.12426 CrossRefGoogle Scholar
- 14.Kjeldsen L, Johnsen AH, Sengeløv H, Borregaard N (1993) Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem 268:10425–10432Google Scholar
- 16.Mishra J, Mori K, Ma Q, Kelly C, Yang J, Mitsnefes M, Barasch J, Devarajan P (2004) Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 15:3073–3082. https://doi.org/10.1097/01.ASN.0000145013.44578.45 CrossRefGoogle Scholar
- 18.Murase K, Mori K, Yoshimura C, Aihara K, Chihara Y, Azuma M, Harada Y, Toyama Y, Tanizawa K, Handa T, Hitomi T, Oga T, Mishima M, Chin K (2013) Association between plasma neutrophil gelatinase associated lipocalin level and obstructive sleep apnea or nocturnal intermittent hypoxia. PLoS One 8:e54184. https://doi.org/10.1371/journal.pone.0054184 CrossRefGoogle Scholar
- 21.James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E (2014) Evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311:507–520. https://doi.org/10.1001/jama.2013.284427 CrossRefGoogle Scholar
- 23.Levey AS, Coresh J, Greene T, Stevens LA, Zhang Y(L), Hendriksen S, Kusek JW, van Lente F, for the Chronic Kidney Disease Epidemiology Collaboration* (2006) Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145:247–254CrossRefGoogle Scholar
- 24.IBER C (2007) Respiratory rules. AASM Man Scoring Sleep Assoc Events Rules Terminol Tech Specif 45–50Google Scholar
- 25.Kiskac M, Zorlu M, Akkoyunlu ME, Kilic E, Karatoprak C, Cakirca M, Yavuz E, Ardic C, Camli AA, Cikrikcioglu M, Kart L (2014) Vaspin and lipocalin-2 levels in severe obsructive sleep apnea. J Thorac Dis 6:720–725. https://doi.org/10.3978/j.issn.2072-1439.2014.06.17 Google Scholar
- 27.Chen Y, Li Y, Jiang Q, Xu X, Zhang X, Simayi Z, Ye H (2015) Analysis of early kidney injury-related factors in patients with hypertension and obstructive sleep apnea hypopnea syndrome (OSAHS). Arch Iran Med 18:827–833Google Scholar
- 33.Marin JM, Carrizo SJ, Vicente E, Agusti AGN (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365:1046–1053. https://doi.org/10.1016/S0140-6736(05)71141-7 CrossRefGoogle Scholar
- 34.Zhao YY, Wang R, Gleason KJ, Lewis EF, Quan SF, Toth CM, Morrical M, Rueschman M, Weng J, Ware JH, Mittleman MA, Redline S, on behalf of the BestAIR Investigators (2017) Effect of continuous positive airway pressure treatment on health-related quality of life and sleepiness in high cardiovascular risk individuals with sleep apnea: Best Apnea Interventions for Research (BestAIR) trial. Sleep 40. https://doi.org/10.1093/sleep/zsx040
- 35.Nicholl DDM, Hanly PJ, Poulin MJ, Handley GB, Hemmelgarn BR, Sola DY, Ahmed SB (2014) Evaluation of continuous positive airway pressure therapy on renin-angiotensin system activity in obstructive sleep apnea. Am J Respir Crit Care Med 190:572–580. https://doi.org/10.1164/rccm.201403-0526OC CrossRefGoogle Scholar
- 37.Marrone O, Cibella F, Pépin J-L, Grote L, Verbraecken J, Saaresranta T, Kvamme JA, Basoglu OK, Lombardi C, McNicholas WT, Hedner J, Bonsignore MR (2018) Fixed but not autoadjusting positive airway pressure attenuates the time-dependent decline in glomerular filtration rate in patients with obstructive sleep apnea. Chest. https://doi.org/10.1016/j.chest.2018.04.020
- 40.Adams RJ, Appleton SL, Vakulin A et al (2017) Chronic Kidney Disease and Sleep Apnea Association of Kidney Disease With Obstructive Sleep Apnea in a population study of men. Sleep 40. https://doi.org/10.1093/sleep/zsw015
- 41.López Gómez JM, Sacristán Enciso B, Micó M et al (2011) Serum cystatin C and microalbuminuria in the detection of vascular and renal damage in early stages. Nefrol 31:560–566. https://doi.org/10.3265/Nefrologia.pre2011.Jul.10834 Google Scholar