IgA肾病肾小球节段性硬化或粘连和肾功能下降的相关性分析

Analysis of association between segmental glomerulosclerosis and renal function decline in IgA nephropathy

目的探讨IgA肾病(IgAN)肾小球节段性硬化或粘连与肾功能变化的关系。方法本研究为单中心回顾性队列研究,选取2011年1月至2018年12月在深圳市第二人民医院住院、经肾活检证实为IgAN的患者。排除继发性IgAN、缺乏基线血肌酐或牛津病理分型数据、基线估算的肾小球滤过率(eGFR)<30 ml·min^-1·(1.73 m^2)^-1、随访时间小于6个月、少于3次以上血肌酐随访数据等患者。收集患者的临床资料和实验室检查、肾脏病理等数据。根据牛津病理分型是否伴肾小球节段性硬化或粘连(S)将患者分为无肾小球节段性硬化或粘连(S0)组和肾小球节段性硬化或粘连(S1)组。采用广义相加混合效应模型分析IgAN患者S和肾功能下降的关系(肾功能评价采用eGFR)。结果共有280例患者入选本研究,其中S0组199例,S1组81例。与S0组相比,S1组患者基线的三酰甘油、血尿酸及24 h尿蛋白量水平更高,eGFR更低,病理表现为肾小管萎缩/间质纤维化(T)的比例更高(均P<0.05)。应用广义相加混合效应模型分析,校正年龄、性别、平均动脉压、24 h尿蛋白量、肾小球系膜细胞增生(M)、毛细血管内细胞增多(E)、T、新月体形成(C)后,S1的效应值(基线S1组和S0组eGFR的差值)为-14.09 ml·min-1·(1.73 m^2)^-1。时间每增加1年,S0组的eGFR平均下降1.29 ml·min^-1·(1.73 m^2)-1(95%CI 0.47~2.12,P=0.002),S1组比S0组的eGFR平均多下降2.85 ml·min^-1·(1.73 m^2)^-1(95%CI 1.05~4.64,P=0.002)。结论IgAN患者肾小球节段性硬化或粘连与长期肾功能下降有关,提示早期治疗节段硬化病变可能对于延缓肾功能下降进展具有重要作用。

Objective To explore the relationship between segmental glomerulosclerosis and the change of renal function in IgA nephropathy(IgAN).Methods It was a single⁃center retrospective cohort study.The patients with biopsy⁃proven primary IgAN who were hospitalized in Shenzhen Second People's Hospital from January 1,2011 to December 31,2018 were included.Participants with a secondary cause of IgAN,without baseline serum creatinine or renal pathology data for Oxford classification,baseline estimated glomerulofiltration rate(eGFR)<30 ml·min^-1·(1.73 m^2)^-1,follow⁃up time<6 months,or less than three times measurements of followed⁃up serum creatinine were excluded.The clinical data,laboratory tests and renal pathology data and so on were collected.Patients were divided into absence of segmental glomerulosclerosis(S0)group and segmental glomerulosclerosis(S1)group according to the Oxford classification.The generalized additive mixed model was used to analyze the associations of segmental glomerulosclerosis and longitudinal renal function decline(Renal function was evaluated by using the eGFR).Results There were 280 patients included in this study,with 199 patients in S0 group,and 81 patients in S1 group.Compared with S0 group,patients in S1 group exhibited higher levels of triglyceride,serum uric acid as well as 24⁃hour urinary protein,and a lower level of eGFR,and had higher proportions of tubular atrophy and interstitial fibrosis(T)(all P<0.05).After adjusting for age,gender,mean arterial pressure,24⁃hour urinary protein,mesangial hypercellularity(M),endocapillary hypercellularity(E),T and crescent(C)in the generalized additive mixed model,the effect value of S1(the difference of baseline eGFR between S1 group and S0 group)was⁃14.09 ml·min^-1·(1.73 m^2)^-1.For every additional year,the eGFR of S0 group decreased 1.29 ml·min^-1·(1.73 m^2)^-1(95%CI 0.47-2.12,P=0.002)in average,and eGFR decline in S1 group had 2.85 ml·min^-1·(1.73 m^2)^-1 more than that in S0 group[95%CI 1.05-4.64,P=0.002].Conclusion Segmental glomerulosclerosis is independently associated with the longitudinal decrease in renal function in patients with IgAN,which suggests therapies targeted for improving the early damages of segmental glomerulosclerosis may be essential to delay the renal function decline progression.