【作者】 王玉；

【导师】 杜丰；

【作者基本信息】 中国医科大学 ， 内科学（专业学位）， 2024， 硕士

【摘要】 目的:ANCA相关性血管炎(AAV)可导致多个器官、组织损伤,出现功能障碍,最常累及肾脏和肺。本研究拟探讨AAV肾损害的危险因素,分析AAV肾损害预后的影响因素,以早期识别AAV肾损害的严重程度、评估疾病预后,为临床诊疗提供依据。研究方法:本研究回顾性地收集2017年1月至2022年12月于中国医科大学附属盛京医院初次确诊为AAV的患者,根据肾脏受累的定义,共筛选出118例AAV肾受累的患者纳入研究。探讨AAV肾损害患者的临床表现、实验室数据与肾功能(以血清肌酐表示)的相关性;根据基线血清肌酐水平是否>500μmol/L分为A组(血清肌酐>500μmol/L,n=49)和B组(血清肌酐≤500μmol/L,n=69)患者,比较两组患者的一般资料、实验室相关数据的差异,探讨AAV肾损害严重程度的影响因素;分析基线临床资料与AAV肾损害患者预后(包括全因性死亡及进展为终末期肾病)的相关性。应用SPSS23.0统计软件,通过相应的统计学方法对数据进行分析讨论。结果:1.本研究共纳入AAV肾损害的患者118例,男性59例(50%),女性59例(50%),男女之比为1:1;平均年龄为65.18岁;肾外表现以系统性表现(44.9%)多见,主要表现为发热、乏力、关节疼痛等,眼/黏膜(1.7%)及神经系统(0.8%)表现较为少见。治疗方面40例患者接受了糖皮质激素联合环磷酰胺或霉酚酸酯诱导治疗,24例(20.3%)患者除诱导治疗外接受了血浆置换治疗。随访期间,30例患者死亡,32例患者进展为终末期肾病,需依赖肾脏替代治疗,其余患者随访期间未出现因疾病复发、病情活动而调整治疗方案。2.通过Spearman秩相关分析探讨AAV肾损害患者的血清肌酐水平与临床参数的相关性,结果发现:血清肌酐与抗髓过氧化物酶抗体、尿红细胞、D二聚体、血尿素氮、血尿酸、胱抑素-C正相关(P<0.05),而与血红蛋白、血小板、活化部分凝血活酶时间、高密度脂蛋白、补体C3、总T细胞及T辅助细胞负相关(P<0.05)。3.AAV肾损害A组和B组组间比较显示:两组间抗髓过氧化物酶抗体、尿红细胞、血红蛋白、血小板、D二聚体、血尿素氮、血尿酸、胱抑素-C、总胆固醇、高密度脂蛋白、估算肾小球滤过率、补体C3、总T细胞和T辅助细胞有统计学差异(P<0.05)。与B组相比,A组患者表现为更高的髓过氧化物酶、尿红细胞、D-二聚体、血尿素氮、血尿酸、胱抑素-C,A组患者的血红蛋白、血小板、估算肾小球滤过率、总胆固醇、高密度脂蛋白、补体C3、T淋巴细胞、T辅助细胞低于B组(P<0.05)。4.多因素Logistic回归分析AAV肾损害严重程度的影响因素显示:血小板(OR=0.989,95%CI 0.979-0.999)、高密度脂蛋白(OR=0.049,95%CI 0.003-0.923)、血尿素氮(OR=1.578,95%CI 1.251-1.992)与AAV肾损害严重程度相关(P<0.05)。5.多因素Cox回归分析AAV肾损害全因性死亡的影响因素,结果显示:基线血清肌酐>500μmol/L与AAV肾损害患者全因性死亡风险增加相关(HR=2.658,95%CI1.204-5.871),而女性性别与AAV肾损害患者较低的全因性死亡风险相关(HR=0.365,95%CI 0.163-0.771)。6.多因素Cox回归分析AAV肾损害进展为终末期肾病的影响因素,结果提示基线血清肌酐>500μmol/L与AAV肾损害患者进展为终末期肾病相关(HR=6.394,95%CI2.561-15.965)。结论:1.较高的基线血尿素氮、较低的基线血小板及高密度脂蛋白与AAV肾损害患者更严重的肾脏损伤相关。2.较高的基线血清肌酐水平与AAV肾损害患者全因性死亡风险增加相关,同时与肾脏预后不良相关。AAV肾损害的患者中,女性性别与较低的全因性死亡风险相关。更多还原

【Abstract】 Objective: Anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV)can lead to damage and dysfunction of multiple organs and tissues,most often involving the kidneys and lungs.In this study,we intend to investigate the risk factors for renal damage in AAV,and analyze the influencing factors of the prognosis of AAV renal damage,in order to identify the severity of AAV renal damage at an early stage,assess the prognosis of the disease,and provide evidence for clinical diagnosis and treatment.Methods: In this study,we retrospectively collected patients who were first diagnosed with AAV at Shengjing Hospital of China Medical University from January 2017 to December 2022,and a total of 118 patients were screened for inclusion in the study according to the definition of renal involvement.To explore the correlation between clinical manifestations,laboratory data and renal function(expressed as serum creatinine)in patients with AAV renal damage.Patients were categorized into group A(serum creatinine >500μmol/L,n=49)and group B(serum creatinine ≤500μmol/L,n=69)according to whether the baseline serum creatinine level was >500μmol/L,and the general data of patients in the two groups were compared.Differences in laboratoryrelated data were investigated to explore the factors influencing the severity of AAV renal damage.The correlation between baseline clinical data and prognosis of patients with AAV renal damage(including all-cause death and progression to end-stage renal disease)was analyzed.SPSS23.0 statistical software was applied to analyze and discuss the data by corresponding statistical methods.Results: 1.A total of 118 patients with AAV renal damage were included in this study,59(50%)males and 59(50%)females,with a male-to-female ratio of 1:1.The mean age was 65.18 years.The extrarenal manifestations were mostly systemic(44.9%),mainly manifested as fever,fatigue,and joint pain,etc.The ocular/mucosal manifestations(1.7%)and nervous system manifestations(0.8%)were rare.In terms of treatment,40 patients received glucocorticoids combined with cyclophosphamide or mycophenolate mofetil induction therapy,and 24 patients(20.3%)received plasma exchange therapy in addition to induction therapy.During the follow-up period,30 patients died,32 patients progressed to end-stage renal disease and needed to rely on renal replacement therapy,and the rest of the patients did not have any adjustment of the treatment regimen due to disease recurrence or disease activity during the follow-up period.2.Spearman correlation analysis was performed to investigate the correlation between serum creatinine level and clinical parameters in patients with AAV renal damage.The results showed that serum creatinine was positively correlated with antimyeloperoxidase antibody,urinary red blood cells,D-dimer,blood urea nitrogen,blood uric acid,and cystatin C(P < 0.05),and negatively correlated with hemoglobin,platelets,activated partial thromboplastin time,high density lipoprotein,complement C3,T lymphocytes and T helper cells(P < 0.05).3.Comparison of AAV renal damage between group A and group B showed: There were statistically significant differences in anti-myeloperoxidase antibodies,urinary red blood cells,hemoglobin,platelets,D-dimer,blood urea nitrogen,blood uric acid,cystatin C,total cholesterol,high density lipoprotein,estimated glomerular filter rate,complement C3,total T cells,and T helper cells between the two groups(P <0.05).Compared with group B,patients in group A showed higher myeloperoxidase,urinary red blood cells,Ddimer,blood urea nitrogen,blood uric acid,cystatin C,and the hemoglobin,platelets,estimated glomerular filtration rate,total cholesterol,high density lipoprotein,complement C3,T lymphocytes,and T helper cells in group A are lower than those in group B(P < 0.05).4.Multivariate Logistic regression analysis of factors affecting the severity of renal damage in AAV showed that platelets(OR=0.989,95% CI 0.979-0.999),high density lipoproteins(OR=0.049,95% CI 0.003-0.923),blood urea nitrogen(OR=1.578,95% CI1.251-1.992)were associated with the severity of AAV renal damage(P < 0.05).5.Multivariate Cox regression analysis of factors influencing all-cause mortality in AAV renal damage showed that baseline serum creatinine >500μmol/L was associated with an increased risk of all-cause mortality in patients with AAV renal damage(HR =2.658,95% CI 1.204-5.871),whereas female gender was associated with a lower risk of all-cause mortality in patients with AAV renal damage(HR = 0.365,95% CI 0.163-0.771).6.Multivariate Cox regression analysis suggested that baseline serum creatinine >500μmol/L was associated with progression to end-stage renal disease in patients with AAV renal damage(HR=6.394,95%CI 2.561-15.965).Conclusion: 1.Higher baseline blood urea nitrogen,lower baseline platelets,and high density lipoprotein were associated with more severe kidney injury in patients with AAV renal damage.2.Higher baseline serum creatinine level was associated with an increased risk of allcause mortality in patients with AAV renal damage,as well as with poor renal outcomes.Among patients with AAV renal damage,female sex was associated with a lower risk of all-cause mortality.更多还原