移植肾局灶节段性肾小球硬化的临床病理特征及预后

Clinicopathological features and allograft outcomes of post-transplant focal segmental glomerulosclerosis

目的:分析移植肾局灶节段性肾小球硬化(FSGS)患者的临床病理特征及预后.方法:回顾性分析国家肾脏疾病临床医学研究中心2013年1月至2019年12月经移植肾活检首次确诊FSGS患者的临床病理及随访资料,将患者分为肾病范围蛋白尿(NP)组和非肾病范围蛋白尿(nNP)组进行比较.结果:共纳入52例移植肾FSGS患者(NP组19例,nNP组33例),移植肾活检距肾移植的中位时间为12.4月,中位尿蛋白2.5 g/24h,血清肌酐203.3μmol/L.经典型FSGS占69.2%,塌陷型、细胞型、顶部型和门部型各占11.5%、7.7%、7.7%和3.8%.55.8%患者硬化袢周围可见足细胞增生,13.5%伴假性新月体形成.电镜下56.3%(18/32)患者可见足突广泛融合.与nNP组相比,NP组患者移植肾活检距肾移植的时间更短,活检时水肿及感染的比例更高,肾小管间质病变和足突融合的程度更重(P均<0.05).11例患者失随访,余41例中位随访16.9月,17例(41.5%)进入终末期肾病,中位肾脏存活29.3月.NP组的移植肾存活率明显低于nNP组(P=0.040).血浆置换和利妥昔单抗(RTX)治疗组、单用RTX组和其他治疗组尿蛋白缓解率分别为60.0%、50.0%和36.4%.结论:移植肾FSGS患者主要表现为中等量蛋白尿和移植肾功能不全;肾移植术后早期发病者,蛋白尿更多、足突融合程度更重,预后更差.

Objective:To explore the clinicopathological features and allograft outcomes of post-transplant focal segmental glomerulosclerosis(FSGS). Methodology:Patients with kidney allograft biopsy-proven FSGS from January 2013 to December 2019 were studied retrospectively and divided into nephrotic-range proteinuria(NP) group and non-nephrotic-range proteinuria(nNP) group for comparative analysis. Results:Fifty-two patients were enrolled(19 cases in NP group and 33 cases in nNP group).Forty-seven(90.4%) were male.The median time from transplantation to allograft biopsy was 12.4 months.The median serum creatinine and proteinuria were 203.3 μmol/L and 2.5 g/24 h.The not otherwise specified(NOS),collapsing, cellular, tip and perihilar variant type of FSGS accounted for 69.2%,11.5%,7.7%,7.7% and 3.8%,respectively.Podocyte hyperplasia was found in 29(55.8%) patients, and pseudocrescents were present in 7(13.5%) patients.Diffuse foot process effacement(FPE) was observed in 18 of 32(56.3%) patients.The NP group was diagnosed earlier after transplantation and had higher incidence of edema and infection at biopsy, and more severe degree of tubulointerstitial lesions and FPE than the nNP group(all P<0.05).Clinical follow-up was available for 41 patients with a median time of 16.9 months, and 17(41.5%) developed allograft failure.Kidney allograft survival rates were significantly lower in the NP group than in the nNP group(P=0.040).Partial or complete remission rates were 60.0%,50.0% and 36.4% in plasma exchange and rituximab(PE+RTX) group, RTX group and non-PE/RTX group, respectively. Conclusion:Patients with post-transplant FSGS mainly presented with moderate proteinuria and allograft dysfunction;those with early onset after transplantation had more proteinuria, more severe foot process effacement and worse allograft survival.