【作者】 李灏；

【导师】 王伟铭；

【作者基本信息】 上海交通大学 ， 内科学（肾脏病学）， 2015， 博士

【摘要】 目的IgA肾病在原发性肾小球疾病中最为常见,有部分患者常常进展至ESRD。本研究通过回顾性分析患者的临床资料和随访情况,探究原发性IgA肾病的临床特点和长期预后,同时,通过前瞻性随机对照研究探讨糖皮质激素联合环磷酰胺或霉酚酸酯治疗伴肾功能损伤原发性IgA肾病的疗效及安全性。方法回顾性分析2002年1月至2013年12月期间于上海交通大学医学院附属瑞金医院肾脏科诊断随访的1052例原发性IgA肾病患者,收集病史、实验室检查、治疗等临床资料,并从中筛选出随访时间达5年的297例患者进行分组研究。通过前瞻性随机对照试验分别比较糖皮质激素及糖皮质激素联合环磷酰胺或霉酚酸酯治疗伴肾功能损伤的IgA肾病的疗效及安全性。结果为进一步探究原发性IgA肾病临床特点及预后,本研究回顾性分析了2002年至2013年间1052例我院成人IgA肾病患者,肾活检确诊后5年的肾脏累计生存率为92%,10年为88%。对随访时间达5年的297例患者进行分组研究,结果显示,肾活检时处于CKD1-3a期患者的肾脏预后较好,CKD3b期患者5年肾脏累计生存率为85.3%,CKD4期患者则只有65.3%。肾活检时的肾功能较差,24小时尿蛋白定量较多,血压较高,伴有贫血和低白蛋白血症可能是IgA肾病进展的危险因素。对于缓慢进展型的IgA肾病目前仍缺乏统一的治疗方案,为探究糖皮质激素联合环磷酰胺治疗伴肾功能损伤的IgA肾病的疗效及安全性,我们将伴肾功能损伤的IgA肾病患者随机入组单纯激素组和CTX组(激素联合环磷酰胺治疗),各60例,随访5年。单纯激素组男女比为36:24,平均年龄38.65±12.53岁,有2例进入主要终点;CTX组男女比为34:26,平均年龄40.15±14.05岁,有11例进入主要终点。两组患者基线资料无明显差异(P>0.05)。在治疗及随访期间,两组各时间点的24小时尿蛋白定量、血清白蛋白等指标均较基线水平明显改善,差异有统计学意义(P<0.05)。CTX组36月时的血肌酐水平(171.27±110.44umol/L)较治疗前(131.57±16.19umol/L)有所上升(P<0.05),且60月时(157.29±83.42umol/L)与基线相比无明显差异(P>0.05);单纯激素组血肌酐水平在60月时(121.47±48.37umol/L)较基线(155.38±70.07umol/L)有所下降(P<0.05)。K-M法分析单纯激素组和CTX组的肾脏平均生存时间分别为(58.49±1.05)月和(53.14±1.93)月,差异有统计学意义(P=0.003)。两组均未见严重不良事件。对于伴有肾功能损伤的原发性IgA肾病患者,糖皮质激素联合霉酚酸酯的疗效目前仍存在一定争议。我们通过前瞻性、随机、对照研究比较单纯激素及激素联合霉酚酸酯的治疗效果,并观察其治疗的安全性。伴肾功能损伤IgA肾病患者随机入组单纯激素组和MMF组(激素联合霉酚酸酯治疗),各30例,随访5年。单纯激素组平均年龄37.63±13.16岁,MMF组平均年龄36.33±13.06岁。两组男女比均为17:13,各有2例进入终末期肾病。两组患者基线资料无明显差异(P>0.05)。在治疗及随访期间,两种方案均能较基线显著地减少尿蛋白、升高血白蛋白(P<0.05),而各个时间点血肌酐和e GFR与基线值相比均无明显差异(P>0.05)。K-M法分析两组患者肾脏生存时间无统计学差异(单纯激素组57.24±1.91月,MMF组56.17±2.43月,P>0.05)。MMF组在治疗3月左右时发生了6例严重的肺部感染。结论我院成人IgA肾病患者肾活检确诊后的5年肾脏累计生存率为92%,10年肾脏累计生存率为88%。肾活检时处于CKD3b期及以上的患者5年肾脏生存率较低,预后也相对较差(P<0.05)。肾活检时的肾功能较差,24小时尿蛋白定量较多,血压较高,伴有贫血和低白蛋白血症可能是IgA肾病进展的危险因素。在治疗伴肾功能损伤的IgA肾病时,糖皮质激素及糖皮质激素联合环磷酰胺或霉酚酸酯均具有降低尿蛋白和稳定肾功能的作用,但加用免疫抑制剂治疗并未显示出明显的额外收益。故治疗上应慎重选择,同时需要对患者进行严密的观察和随访。更多还原

【Abstract】 ObjectivePrimary IgA nephropathy is the most common primary glomerulonephritis in China.It is the main cause of end-stage renal disease.In this study we try to investigate the clinical characteristics and the long-term outcomes of patients with primary IgA nephropathy through the retrospective analysis of their clinical data.We conduct RCTs to evaluate the safety and effect of glucocorticoid combined with or without cyclophosphamide or mycophenolate mofetil in the treatment of primary IgA nephropathy patients with impaired renal function.MethodsPatients with biopsy-proved primary IgA nephropathy hospitalized in Department of Nephrology in Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine from January 2002 to December 2013 were included in the retrospective analysis.We collected medical history,laboratory test reports and other clinical data.Then we enrolled the patients who were followed up for 5 years.The patients’ outcome and renal survival were analyzed.Through the prospective randomized controlled trial,we try to compare the safety and effect of glucocorticoid combined with or without cyclophosphamide or mycophenolate mofetil in the treatment of IgAnephropathy patients with impaired renal function.ResultsPrimary IgA nephropathy has various clinical manifestations and pathological performance.In order to further explore the clinical characteristics and outcomes,this study retrospectively analyzed 1052 cases with primary IgA nephropathy from 2002 to2013.Five-year renal survival rate of patients with primary IgA nephropathy was 92%,and ten-year renal survival rate was 88%.We enrolled 297 patients who were followed up for 5 years.The results show that patients with CKD1-3a stage by the time of renal biopsy can have a better outcome.The 5-year renal survival rate of patients with CKD3 b stage was 85.3%,while it is only 65.3% for patients with CKD4 stage.Progressive IgA nephropathy is still lack of certain treatment.We try to evaluate the safety and effect of glucocorticoid combined with or without cyclophosphamide in the treatment of primary IgA nephropathy patients with impaired renal function.A total of120 patients were randomized into two groups.Both CTX group(glucocorticoid combined with cyclophosphamide)and glucocorticoid group(glucocorticoid alone)had60 cases in each group.These patients were followed up for 5 years.In the glucocorticoid group,the sex ratio is 36 males to 24 females and the average age was38.65±12.53 years old.Eleven cases in this group progressed to the following end point.While in CTX group the sex ratio is 34:26 and the average age was 40.15±14.05 years old.Two cases in CTX group proceed to the following end point.The baseline between the two groups of patients didn’t have significant difference(P>0.05).During the treatment and the follow-up,24-hour proteinuria,serum albumin and other indicators of each time point in both groups improved significantly compared with the baseline,meanwhile the difference was statistically significant(P<0.05).Serum creatinine of CTX group was(171.27±110.44umol/L)at the 36 th month which is statistically different from baseline(131.57±16.19umol/L)(P<0.05).And serum creatinine at the 60 th month(157.29±83.42umol/L)did not show any significant difference(P>0.05).Serum creatinine(121.47±48.37umol/L)in glucocorticoid group at the 60 th month was decreased compared with the baseline(155.38±70.07umol/L)(P<0.05).The renal survival time of the glucocorticoid group and the CTX group were(58.49±1.05)months and(53.14±1.93)months by K-M method,and the difference was statistically significant(P=0.003).Serious adverse effects were not found in the two groups.For the treatment of primary IgA nephropathy patients with impaired renal function,the effect of glucocorticoid combined with mycophenolate mofetil is still controversial.We try to evaluate the safety and effect of glucocorticoid combined with mycophenolate mofetil in the treatment of primary IgA nephropathy patients with impaired renal function.A total of 60 patients were randomized into two groups.Both MMF group(glucocorticoid combined with MMF)and glucocorticoid group(glucocorticoid alone)had 30 cases in each group.These patients were followed up for 5 years.The average age was 37.63 ±13.16 years old in glucocorticoid group and 36.33±13.06 years old in MMF group.Sex ratio of two groups was 17:13,each group had 2 cases reached to end-stage renal disease.The baseline between the two groups of patients didn’t have significant difference(P>0.05).During the treatment and follow-up,in both two groups,proteinuria showed significantly reduced and serum albumin increased compared with the baseline(P<0.05),while there were no significantly different(P > 0.05)in serum creatinine and e GFR.By K-M method,renal survival time of two groups was nostatistical difference(57.24±1.91 months in glucocorticoid group,56.17 ±2.43 months in MMF group,P > 0.05).Six patients in MMF group suffered from severe pulmonary infection.ConclusionsFive-year renal survival rate of patients with primary IgA nephropathy was 92% in our hospital,and the ten-year renal survival rate was 88%.Patients in CKD3 b or CKD4 stage at the time of renal biopsy may have a worse outcome.In the treatment of IgA nephropathy patients with impaired renal function,glucocorticoid combined with or without cyclophosphamide or mycophenolate mofetil showed a certain effect on improving the proteinuria and renal function,but immunosuppressant did not show extra benefit.The immunosuppressant should be applied to these patients carefully,and a more strict observation and follow-up for the patients should be conducted.更多还原