血清成纤维生长因子-23/抗衰老基因Klotho、辅助性T淋巴细胞1/辅助性T淋巴细胞2细胞因子在老年终末期肾病患者中的表达及对医院感染的预测和预后的影响

Expressions of serum fibroblast growth factor-23/anti-aging gene Klotho,helper T lymphocyte 1/helper T lymphocyte 2 cytokines in elders with end-stage renal disease and their impacts on the prediction and prognosis of hospital-acquired infection

目的观察血清成纤维生长因子-23(fibroblast growth factor 23,FGF23)/抗衰老基因Klotho、辅助性T淋巴细胞(helper T lymphocytes,Th)1/Th2细胞因子在老年终末期肾病患者中的表达,并分析对医院感染的预测和预后的影响。方法选取2021年1月1日至2022年12月31日自贡市精神卫生中心(自贡市老年病医院)收治的106例老年终末期肾病患者,男65例,年龄范围60~84岁,年龄(67.21±3.07)岁,女41例,年龄范围60~84岁,年龄(67.65±2.98)岁,于入院第2天检测血清FGF23、抗衰老基因Klotho、Th1细胞因子[γ干扰素(interferon-γ,IFN-γ)、白介素2(interleukin-2,IL-2)]、Th2细胞因子(IL-4、IL-10)水平,进行急性生理功能及慢性健康状况评分Ⅱ(acute physiology and chronic health status scoring systemⅡ,APACHEⅡ)评估。根据住院期间是否发生医院感染分为感染组(28例)、未感染组(78例),比较两组各项血清指标及APACHEⅡ评分水平,分析各项指标与APACHEⅡ评分的相关性。随访3个月统计患者生存预后[生存(71例)、死亡(35例)],比较不同预后患者血清FGF23、Klotho、IFN-γ、IL-2、IL-4、IL-10水平,分析各项指标对医院感染及预后的预测价值及临床效用。结果106例老年终末期肾病患者根据住院期间是否发生医院感染分为感染组(28例)、未感染组(78例),随访3个月后生存71例、死亡35例。入院第2天感染组血清FGF23、IL-4、IL-10水平及APACHEⅡ评分分别为(78.64±20.16)ng/mL、(20.14±1.48)μg/L、(22.47±2.56)μg/L、(26.38±6.51)分,未感染组分别为(60.17±16.83)ng/mL、(16.25±1.21)μg/L、(19.52±1.86)μg/L、(22.97±6.45)分,感染组血清FGF23、IL-4、IL-10水平及APACHEⅡ评分均高于未感染组(P<0.05);入院第2天感染组血清Klotho、IFN-γ、IL-2水平分别为(34.95±12.62)ng/mL、(22.19±1.69)μg/L、(28.73±2.95)μg/L,未感染组分别为(51.61±16.08)ng/mL、(25.31±1.74)μg/L、(33.95±1.52)μg/L,感染组血清Klotho、IFN-γ、IL-2水平均低于未感染组(P<0.05);血清FGF23、IL-4、IL-10水平与APACHEⅡ评分呈正相关(相关系数r=0.629、0.597、0.612,P均<0.05),血清Klotho、IFN-γ、IL-2水平与APACHEⅡ评分呈负相关(相关系数r=-0.632、-0.718、-0.701、0.597,P均<0.05);死亡患者入组后1个月血清FGF23、IL-10、IL-4水平分别为(77.49±21.85)ng/mL、(24.76±4.77)μg/L、(24.81±6.28)μg/L,生存患者分别为(58.92±16.94)ng/mL、(18.10±3.82)μg/L、(13.57±4.38)μg/L,死亡患者入组后1个月血清FGF23、IL-10、IL-4水平高于生存患者(P<0.05);死亡患者入组后1个月血清Klotho、IFN-γ、IL-2水平分别为(30.03±11.76)ng/mL、(20.33±2.63)μg/L、(27.19±4.91)μg/L,生存患者分别为(55.68±17.02)ng/mL、(26.54±4.79)μg/L、(35.22±5.64)μg/L,死亡患者入组后1个月血清Klotho、IFN-γ、IL-2水平低于生存患者(P<0.05);血清FGF23、Klotho、IFN-γ、IL-2、IL-4、IL-10预测终末期老年肾病患者发生医院感染、生存预后曲线下面积分别为0.904(OR:0.832~0.953)、0.911(OR:0.840~0.958),且具有良好临床效用(P<0.05)。结论老年终末期肾病患者血清FGF23/Klotho、Th1/Th2细胞因子水平失衡,合并感染患者血清FGF23、IL-10、IL-4水平异常升高,血清Klotho、IFN-γ、IL-2水平表达降低,联合血清FGF23/Klotho、Th1/Th2细胞因子预测医院感染、评估预后的价值较高。

Objective To observe the expression of serum fibroblast growth factor 23(FGF23)/anti-aging gene Klotho and helper T lymphocyte(Th)1/Th2 cytokines in elders with end-stage renal disease(ESRD)and analyze their impact on the prediction and prognosis of hospital-acquired infection.Methods From January 1,2021 to December 31,2022,106 ESRD elders hospitalized into Zigong Mental Health Center(Zigong Geriatric Hospital)were recruited.There were 65 males with an average age of(67.21±3.07)(60-84)year and 41 females with an average age of(67.65±2.98)(60-84)year.Serum levels of FGF23,Klotho,Th1 cytokines[interferon-gamma(IFN-γ)&interleukin-2(IL-2)]and Th2 cytokines(IL-4&IL-10)were measured at Day 2 post-admission,acute physiology&chronic health status scoring system II(APACHE II)was evaluated.According to whether or not hospital-acquired infection occurred during hospitalization,they were assigned into two groups of infection(n=28)and non-infection(n=78).Various serum parameters and APACHE II scores of two groups were compared and the correlation between each parameter and APACHE II score was analyzed.Survival status was statistically analyzed after a 3-month follow-up.Serum levels of FGF23,Klotho,IFN-γ,IL-2,IL-4 and IL-10 were compared among patients with different prognoses.Predictive value and clinical utility of each indicator for hospital infection and prognosis were analyzed.Results A total of 106 ESRD elders were divided into two groups of infection(n=28)and non-infection(n=78)based upon whether or not hospital-acquired infection occurred during hospitalization.After a follow-up period of 3 months,71 patients survived and 35 patients died.At Day 2 post-admission,serum levels of FGF23,IL-4,IL-10 and APACHE II scores were(78.64±20.16)ng/mL,(20.14±1.48)μg/L,(22.47±2.56)μg/L and(26.38±6.51)points in infection group versus(60.17±16.83)ng/mL,(16.25±1.21)μg/L,(19.52±1.86)μg/L and(22.97±6.45)points in non-infection group.Serum levels of FGF23,IL-4,IL-10 and APACHE II scores were higher in infection group than those in non-infection group(P<0.05).At Day 2 post-admission,serum levels of Klotho,IFN-γand IL-2 were(34.95±12.62)ng/mL,(22.19±1.69)μg/L and(28.73±2.95)μg/L in infection group versus(51.61±16.08)ng/mL,(25.31±1.74)μg/L and(33.95±1.52)μg/L in non-infection group.Serum levels of Klotho,IFN-γand IL-2 in infection group were lower than those in non-infection group(P<0.05).Serum levels of FGF23,IL-4 and IL-10 were correlated positively with APACHE II score(correlation coefficients r=0.629,0.597 and 0.612,all P<0.05)while serum levels of Klotho,IFN-γand IL-2 negatively with APACHE II score(correlation coefficients r=−0.632,−0.718,−0.701 and 0.597,all P<0.05).Serum levels of FGF23,IL-10 and IL-4 were(77.49±21.85)ng/mL,(24.76±4.77)μg/L and(24.81±6.28)μg/L in deceased patients versus(58.92±16.94)ng/mL,(18.10±3.82)μg/L and(13.57±4.38)μg/L in survivors.Serum levels of FGF23,IL-10 and IL-4 were higher in deceased patients than those in survivors at Month 1 post-enrollment(P<0.05).At Month 1 post-enrollment,serum levels of Klotho,IFN-γand IL-2 were(30.03±11.76)ng/mL,(20.33±2.63)and(27.19±4.91)μg/L in deceased patients versus were(55.68±17.02)ng/mL,(26.54±4.79)μg/L and(35.22±5.64)μg/L in survivors.Serum levels of Klotho,IFN-γand IL-2 were lower in deceased patients than those in survivors(P<0.05).The areas under receiver operating characteristic(ROC)curve for serum levels of FGF23,Klotho,IFN-γ,IL-2,IL-4 and IL-10 in predicting the occurrence of hospital infection and survival status in ESRD patients were 0.904(OR:0.832-0.953)and 0.911(OR:0.840-0.958)with excellent clinical utilities(P<0.05).Conclusion In ESRD elders,an imbalance of serum FGF23/Klotho and Th1/Th2 cytokine levels,abnormal elevations in serum levels of FGF23,IL-10 and IL-4 and lower serum levels of Klotho,IFN-γand IL-2 are highly predictive of hospital-acquired infection and prognosis.