髓过氧化物酶抗中性粒细胞胞质抗体相关性肾小球肾炎患者的临床病理特征及肾脏预后分析

Analysis of clinicopathological characteristics and renal prognosis of patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated glomerulonephritis

目的:研究髓过氧化物酶(myeloperoxidase,MPO)抗中性粒细胞胞质抗体(anti-neutrophil cytoplasmic antibody,ANCA)相关性肾小球肾炎(MPO-ANCA-glomerulonephritis,MPO-ANCA-GN)患者的临床病理特征以及患者肾脏预后的相关因素。方法:收集2005年1月至2018年12月在南京医科大学附属第一医院住院的172例MPO-ANCA-GN患者。回顾性分析患者的基线临床特征、肾活检病理特征,且对患者的肾脏预后进行随访。分析所有患者不同肾脏预后的临床特征及接受肾活检的112例患者的病理特征,并进一步探讨影响肾脏生存的相关因素。结果:172例患者中男81例,女91例,年龄为66.0(59.0,72.0)岁,诊断时的血清肌酐为343.7(174.2,606.6)μmol/L,估算肾小球滤过率(estimated glomerular filtration rate,eGFR)为15.81(7.61,38.04)ml·min^(-1)·(1.73 m ^(2))^(-1)。76例(44.2%)患者接受了初始肾替代治疗(renal replacement therapy,RRT)。经过20(3,60)个月的随访,73例(42.4%)患者进展为终末期肾病(end-stage renal disease,ESRD)需依赖透析,其中包括6例(8.2%)随访过程中进入RRT的患者和67例(91.8%)初始即接受RRT的患者。接受肾活检的112例患者中,硬化型组进展为ESRD的患者比例最高(15/25,60.0%)。非透析依赖组的基线血清肌酐水平(P<0.001)、尿红细胞计数(P=0.012)和球性废弃比例(P=0.002)均明显低于透析依赖组,而eGFR(P<0.001)、血清白蛋白(P=0.002)和血红蛋白(P<0.001)水平均高于透析依赖组。Kaplan-Meier生存分析显示,局灶型组患者的肾脏生存率最高(χ^(2)=19.488,P<0.001),而硬化型组的肾脏生存率显著低于新月体型组(χ^(2)=5.655,P=0.017);较高的血清肌酐(>320μmol/L,χ^(2)=77.229,P<0.001)和尿红细胞计数(>300个/μl,χ^(2)=8.511,P=0.004)水平,较低的类风湿因子(<20 IU/ml,χ^(2)=8.610,P=0.003)、血清白蛋白(<30 g/L,χ^(2)=11.060,P=0.001)和血红蛋白(<90 g/L,χ^(2)=21.921,P<0.001)水平与较低的肾脏生存率相关;在治疗方面,糖皮质激素加霉酚酸酯组的肾脏生存率显著高于糖皮质激素加环磷酰胺(χ^(2)=5.056,P=0.025)和单独使用糖皮质激素组(χ^(2)=16.459,P<0.001)。多因素Cox回归分析结果显示,基线血清肌酐水平>320μmol/L(HR=8.803,95%CI 3.087~25.106,P<0.001)和血清白蛋白<30 g/L(HR=2.566,95%CI 1.246~5.281,P=0.011)是患者进展至ESRD的影响因素。结论:MPO-ANCA-GN患者诊断时的血清肌酐和血清白蛋白水平可能是影响患者肾脏预后的相关因素。

Objective To determine the prognostic values of clinical and laboratory features at the time of presentation on renal survival of patients with myeloperoxidase(MPO)-antineutrophil cytoplasmic antibody(ANCA)-associated glomerulonephritis(MPO-ANCA-GN).Methods A total of 172 patients with MPO-ANCA-GN and hospitalized at the First Affiliated Hospital of Nanjing Medical University from January 2005 to December 2018 were enrolled.The baseline clinical characteristics and renal biopsy pathological data were analyzed,and the renal prognosis was followed up.The clinical and pathological characteristics of different renal prognosis in all patients and 112 patients who underwent renal biopsy were analyzed,and the related factors affecting renal survival were further discussed.Results Among these 172 patients,81 were males and 91 were females.The median serum creatinine at diagnosis was 343.7(174.2,606.6)μmol/L and the median estimated glomerular filtration rate(eGFR)was 15.81(7.61,38.04ml·min^(-1)·(1.73 m ^(2))^(-1).In total,76 patients(44.2%)received initial renal replacement therapy(RRT).During a median follow-up duration of 20(3,60)months,73 patients(42.4%)progressed to end-stage renal disease(ESRD)and required dialysis,including 6(8.2%)patients who entered RRT during follow-up and 67(91.8%)patients who received RRT at the beginning.Among the 112 patients who underwent renal biopsy,the proportion of patients who progressed to ESRD in the sclerotic group was the highest(15/25,60.0%).The baseline serum creatinine level(P<0.001),urine red blood cell count(P=0.012)and the proportion of glomerular sclerosis(P=0.002)in the non-dialysis dependent group were significantly lower than those in the dialysis dependent group,while the levels of eGFR(P<0.001),serum albumin(P=0.002)and hemoglobin(P<0.001)were higher than those of the dialysis-dependent group.Kaplan-Meier survival analysis showed that the renal survival rate of the focal group was the highest(χ^(2)=19.488,P<0.001,log-rank test),while the renal survival rate of the sclerotic group was significantly lower than that of the crescentic group(χ^(2)=5.655,P=0.017);higher levels of serum creatinine(>320μmol/L,χ^(2)=77.229,P<0.001)and urine red blood cell count(>300 cells/μl,χ^(2)=8.511,P=0.004),lower levels of rheumatoid factor(<20 IU/ml,χ^(2)=8.610,P=0.003),serum albumin(<30 g/L,χ^(2)=11.060,P=0.001)and hemoglobin(<90 g/L,χ^(2)=21.921,P<0.001)were associated with lower renal survival rate;in terms of treatment,the renal survival rate of the glucocorticoids plus mycophenolate mofetil group was significantly higher than that of the glucocorticoids plus cyclophosphamide(χ^(2)=5.056,P=0.025)or the glucocorticoids alone group(χ^(2)=16.459,P<0.001).Multivariate Cox regression showed that baseline serum creatinine>320μmol/L(HR=8.803,95%CI 3.087-25.106,P<0.001)and serum albumin<30 g/L(HR=2.566,95%CI 1.246-5.281,P=0.011)were the related factors affecting renal survival.Conclusion Serum creatinine and albumin levels of MPO-ANCA-GN patients at diagnosis may be the related factors that affect the patient's renal prognosis.