Journal of Shanghai Jiao Tong University (Medical Science) >
Characteristics and clinical significance of serum renalase in patients with acute ischemic stroke
Received date: 2022-07-06
Accepted date: 2022-09-26
Online published: 2022-10-20
Supported by
National Natural Science Foundation of China(82071283);Shanghai Natural Science Foundation(22ZR1437700)
Objective ·To examine the level change of serum renalase in the patients with acute ischemic stroke (AIS), and analyze its role in evaluating disease. Methods ·A total of 118 AIS patients admitted to the Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from July 2020 to November 2021 were enrolled in the case group (AIS group). The patients were assessed for neurological deficits according to the National Institutes of Health Stroke Scale (NIHSS), and were classified as mild and moderate-severe neurological deficits. Another 133 healthy people who participated in physical examination in the physical examination center of the hospital during the same period were selected as the control group. The serum renalase levels of the two groups were detected by ELISA. Spearman's rank correlation analysis was used to evaluate the correlation between the levels of serum renalase and gender, age, fasting blood glucose, blood lipids and NIHSS scores in the patient with AIS. The predictive value of renalase expression level in AIS diagnosis was analyzed by receiver operator characteristic (ROC) curve. The factors that were statistically significant in the results of the univariate Logistic regression analysis were included in the multivariate Logistic regression model. Results ·The level of serum renalase in the AIS group was 2 960.01 (1 557.99, 4 053.70) pg/mL, which was higher than 821.02 (391.29, 1 752.70) pg/mL in the control group, with a statistically significant difference (P=0.000). Spearman's rank correlation analysis showed that the levels of serum renalase in the patients with AIS were negatively correlated with the NIHSS scores (r=-0.216, P=0.019), positively correlated with the serum fasting glucose (r=0.200, P=0.030), and not significantly correlated with gender, age, low-density lipoprotein levels, total cholesterol levels, and the presence of hypertension, diabetes, or coronary heart disease. Serum renalase levels were higher in the AIS with mild neurological deficit patients than those in the moderate-severe deficit patients, and the difference was statistically significant (P=0.034). The ROC curve showed that the cut-off value of serum renalase level to diagnose AIS was 1 856.49 pg/mL, the area under the curve was 0.777±0.030 and its 95%CI was 0.718?0.836 (P=0.000). Multivariate Logistic regression analysis showed that elevated serum renalase level [>1 856.49 pg/mL, odds ratio (OR)=6.980, P=0.000], hypertension (OR=5.382, P=0.000), and diabetes (OR=2.453, P=0.040) were risk factors for AIS. Conclusion ·Serum renalase level is significantly elevated in AIS patients, and negatively correlated with NIHSS score. Serum renalase might be a potential biomarker for the auxiliary diagnosis and assessment of AIS, providing new ideas for the assessment of stroke disease progression and precise treatment.
Key words: renalase; acute ischemic stroke (AIS); biomarker; NIHSS score
Wenqun JIANG , Pinpin HOU , Yan CHEN , Feng JIA , Xiaohua ZHANG , Li GAO , Qin HU . Characteristics and clinical significance of serum renalase in patients with acute ischemic stroke[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023 , 43(1) : 29 -35 . DOI: 10.3969/j.issn.1674-8115.2023.01.004
1 | GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990?2016: a systematic analysis for the Global Burden of Disease Study 2016[J]. Lancet Neurol, 2019, 18(5): 459-480. |
2 | KAMTCHUM-TATUENE J, JICKLING G C. Blood biomarkers for stroke diagnosis and management[J]. Neuromolecular Med, 2019, 21(4): 344-368. |
3 | XU J C, LI G Y, WANG P L, et al. Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure[J]. J Clin Invest, 2005, 115(5): 1275-1280. |
4 | FEDCHENKO V, GLOBA A, BUNEEVA O, et al. Renalase mRNA levels in the brain, heart, and kidneys of spontaneously hypertensive rats with moderate and high hypertension[J]. Med Sci Monit Basic Res, 2013, 19: 267-270. |
5 | MORAN G R, HOAG M R. The enzyme: renalase[J]. Arch Biochem Biophys, 2017, 632: 66-76. |
6 | SEVERINA I S, FEDCHENKO V I, VESELOVSKY A V, et al. The history of renalase from amine oxidase to a a-NAD(P)H-oxidase/anomerase[J]. Biomed Khim, 2015, 61(6): 667-679. |
7 | WANG Y, SAFIRSTEIN R, VELAZQUEZ H, et al. Extracellular renalase protects cells and organs by outside-in signalling[J]. J Cell Mol Med, 2017, 21(7): 1260-1265. |
8 | LI Y, WU W D, LIU W H, et al. Roles and mechanisms of renalase in cardiovascular disease: a promising therapeutic target[J]. Biomed Pharmacother, 2020, 131: 110712. |
9 | ZHANG R Y, LI X Y, LIU N N, et al. An association study on renalase polymorphisms and ischemic stroke in a Chinese population[J]. Neuromolecular Med, 2013, 15(2): 396-404. |
10 | LI X Y, WANG Z Z, LIU Y, et al. Association of imaging classification of intracranial cerebral atherosclerotic vascular stenosis in ischemic stroke and renalase gene polymorphisms[J]. J Mol Neurosci, 2014, 52(4): 461-466. |
11 | RAMROODI N, KHORRAMI A, HASHEMI S M, et al. The effect of renalase rs2576178 and rs10887800 polymorphisms on ischemic stroke susceptibility in young patients (<50 years): a case-control study and in silico analysis[J]. Dis Markers, 2021, 2021: 5542292. |
12 | 中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性缺血性脑卒中诊治指南2018[J]. 中华神经科杂志, 2018, 51(9): 666-682. |
12 | Chinese Society of Neurology, Chinese Stroke Society. Chinese guidelines for the diagnosis and treatment of acute ischemic stroke 2018[J]. Chinese Journal of Neurology, 2018, 51(9): 666-682. |
13 | MENDELSON S J, PRABHAKARAN S. Diagnosis and management of transient ischemic attack and acute ischemic stroke: a review[J]. JAMA, 2021, 325(11): 1088-1098. |
14 | SAFDAR B, GUO X J, JOHNSON C, et al. Elevated renalase levels in patients with acute coronary microvascular dysfunction: a possible biomarker for ischemia[J]. Int J Cardiol, 2019, 279: 155-161. |
15 | LEE H T, KIM J Y, KIM M, et al. Renalase protects against ischemic AKI[J]. J Am Soc Nephrol, 2013, 24(3): 445-455. |
16 | GUO X J, XU L Y, VELAZQUEZ H, et al. Kidney-targeted renalase agonist prevents cisplatin-induced chronic kidney disease by inhibiting regulated necrosis and inflammation[J]. J Am Soc Nephrol, 2022, 33(2): 342-356. |
17 | BARAKA A, EL GHOTNY S. Cardioprotective effect of renalase in 5/6 nephrectomized rats[J]. J Cardiovasc Pharmacol Ther, 2012, 17(4): 412-416. |
18 | WANG F, CAI H Y, ZHAO Q, et al. Epinephrine evokes renalase secretion via α?adrenoceptor/NF?κB pathways in renal proximal tubular epithelial cells[J]. Kidney Blood Press Res, 2014, 39(4): 252-259. |
19 | DESIR G V, WANG L, PEIXOTO A J. Human renalase: a review of its biology, function, and implications for hypertension[J]. J Am Soc Hypertens, 2012, 6(6): 417-426. |
20 | AOKI K, YANAZAWA K, TOKINOYA K, et al. Renalase is localized to the small intestine crypt and expressed upon the activation of NF-κB p65 in mice model of fasting-induced oxidative stress[J]. Life Sci, 2021, 267: 118904. |
21 | MELOUX A, RIGAL E, ROCHETTE L, et al. Ischemic stroke increases heart vulnerability to ischemia-reperfusion and alters myocardial cardioprotective pathways[J]. Stroke, 2018, 49(11): 2752-2760. |
22 | WANG F, LI J H, XING T, et al. Serum renalase is related to catecholamine levels and renal function[J]. Clin Exp Nephrol, 2015, 19(1): 92-98. |
23 | DESIR G V, TANG L Q, WANG P L, et al. Renalase lowers ambulatory blood pressure by metabolizing circulating adrenaline[J]. J Am Heart Assoc, 2012, 1(4): e002634. |
24 | STOJANOVIC D, MITIC V, STOJANOVIC M, et al. The partnership between renalase and ejection fraction as a risk factor for increased cardiac remodeling biomarkers in chronic heart failure patients[J]. Curr Med Res Opin, 2020, 36(6): 909-919. |
25 | SCHLAICH M P, LAMBERT G W, EIKELIS N. Renalase: a potential biomarker for risk of atrial fibrillation?[J]. Kardiol Pol, 2018, 76(8): 1201-1202. |
26 | HE B H, HAO J J, SHENG W W, et al. Correlation between plasma renalase level and coronary artery disease[J]. Pak J Med Sci, 2014, 30(5): 863-967. |
27 | LIBRUDER C, RAM A, HERSHKOVITZ Y, et al. The contribution of potentially modifiable risk factors to acute ischemic stroke burden: comparing young and older adults[J]. Prev Med, 2022, 155: 106933. |
28 | BURACZYNSKA M, ZUKOWSKI P, BURACZYNSKA K, et al. Renalase gene polymorphisms in patients with type 2 diabetes, hypertension and stroke[J]. Neuromolecular Med, 2011, 13(4): 321-327. |
29 | BURACZYNSKA M, GWIAZDA-TYNDEL K, DROP B, et al. Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus[J]. Acta Diabetol, 2021, 58(12): 1595-1602. |
30 | CZUBILI?SKA-?ADA J, GLIWI?SKA A, BADE?SKI A, et al. Associations between renalase concentration and the occurrence of selected diseases[J]. Endokrynol Pol, 2020, 71(4): 334-342. |
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