狼疮性肾炎治疗展课件-.ppt

1、狼疮性肾炎治疗进展SLEn6075 狼疮性肾炎（LN）n100 病理学上改变 SLE预后因素n 严重发作n 社会经济地位低n 高AI、CIn 未控制的高血压n 起始治疗反应差n 依从性差n 种族n LN Multivariate analysis of predictors of good long term renal outcomevariantsPOR95%CLAge(30 years)Gender(F)Baseline diastolic pressure(90mmHg)Baseline serum creatinine(1.4mg/dL)Baseline serum albumin(

2、3g/dL)Baseline 24h proteinuria(3g)WHO classes(III or V)Activity index(10)Chronicity index(1)Treatment(HD IV CTX)ACEI used(yes)Serum creatinine at 6 months(drop)0.0114.92.0 11.824h proteinuria at 6 months (0.05)n 71%(LD)缓解 27(LD)复发n 54%(HD)缓解 29%(HD)复发n 感染发生率 HD:LD=2:1P+MMF vs.P+CYC(Aza)(诱导6月，维持6月）Ch

3、an TM et al.N Engl J Med 2000Figure 1.Mean(SD)Serum C3 and Creatinine Concentrations in Patients with Diffuse Proliferative Lupus Nephritis Who Were Treated with Mycophenolate Mofetil and Prednisolone(Group 1)or with Cyclophosphamide and Prednisolone Followed by Azathioprine and Prednisolone(Group 2

4、).Figure 2.Mean(SD)Serum Albumin Concentration and Urinary Protein Excretion in Patients with Diffuse Proliferative Lupus Nephritis Who Were Treated with Mycophenolate Mofetil and Prednisolone(Group 1)or with Cyclophosphamide and Prednisolone Followed by Azathioprine and Prednisolone(Group 2).n81%CR

5、+14%PR in MMF,15%复发，19感染n76CR+14%PR in CYC,11%复发，19感染n （P0.29）nIn CYC：23 停经 10 WBC减少 19 脱发 10 死亡 59 LN(12 Class III,46 IV,1 V)0.51g/m2 IV CYC monthly7GC 0.5mg/kg/d(13yrs)MMF0.53g/dAza13mg/kg/dIV CYC0.51g/m2/3m72months 随访Contreras G et al.N Engl J Med 2019,350:971-980Fig.3.Kaplan-Meier Estimates of P

6、atient Survival Fig.4.KaplanMeier Estimates of Event-free Survival Fig.5.KaplanMeier Estimates of Relapse-free Survival副作用（%）050100停经感染恶心呕吐AzaMMFCYC P0.05 P0.01 P0.01 P8%in P(50m)30%in P+OP CYCIllei et al 2019145 III(22),IV(118)IV-MP,IV-CYC both45%12yrsCiruelo et al 201948II(2),III IV(42)PO CYC or I

7、V CYC+P25%5yrs,46%10yrsIoannidis et al200085III(33),IV(52)P+IV-CYC27%19mHoussiau et al201990III(21),IV(62),V(7)P+IV-CYC Aza28%41mLN复发的危险因素n 青年n 男性n 黑人n 重症狼疮n 动脉高压n 高活动评分n 开始治疗延误n 缓解延迟n 部分反应n 低C4n 抗ds-DNA升高对LN治疗的再认识n PIV CYC仍常用n PMMF等效，毒性低n 诱导缓解时间短？n 维持治疗n Aza或MMF疗效高于IV CYCn 口服CYC累积量提高，性腺抑制n 维持治疗时间长？

8、重症难治性LN治疗策略n血浆置换或免疫吸附联合诱导治疗n非清髓性化疗n干细胞移植（清髓性）非清髓性诱导治疗朱。女，25岁。SLE病程3年。肾活检 IV LNBP160、105mmHgCTX累积用量4.8g骁悉 2g/d+P(1年）诱导治疗 P(20mg/d)+CTX 2.2g诱导治疗后血细胞的变化Plt0204060801001201401609.130天(9.20)9.2610.310.810.21日期109WBC01234569.130天(9.20)9.2610.310.810.21日期10924小时尿蛋白的变化血清Cr,BUN的变化SPECT检测GFRSLE与干细胞移植T,B细胞高度活化

9、HSC transfer ADCD34+apoptosis Papadaki HA,et al.(2019)Br J Haematol 115:167-174.SLE(CD34+)SLE-HSCsSun Lingyun et al Clin Rheumatol Comparison of BM CD34+cells surface markers between SLE patients and normal control*P0.05 vs normalSLE-CD34+The expression percentage of CD166 on BM CD34+cells correlate

10、d with SLEDAI scorer=0.480，P=0.026SLE-HSCsThe expression percentage of CD123 on BM CD34+cells correlated with WBC countr=0.700 P=0.03SLE-HSCsSLE-SLE-Mesenchymal Stem Cells Mesenchymal Stem Cells，MSCsMSCs生物学特性来源广泛自我更新、多向分化潜能易扩增传代能力MSCsIL-6,IL-7,IL-10,IL-11,SCF,SDF-1GM-CSF,M-CSF.adipocyteosteocytechon

11、drocytemyoblastcardiocyteNerve cellhepatocyte可来源于骨髓、胰腺、皮肤、肺脏等多处器官组织 体外能够传40代，并保持稳定的表型和多向分化的潜能 SLE 骨髓MSC 异常原代生长缓慢细胞因子分泌异常:IL-6,IL-7凋亡增加传代减少 Sun Lingyun,et al Lupus,2019,16:121-128MSCsMSCs的免疫调节作用的免疫调节作用 MSC-mediated modulation of cells involved in the immune response:the bidirectional interaction betw

12、een MSC,T cells,B cells andNK cells is described.In the case of DC,the influence of DC on MSC has not yet been proven.The effects ofimmune cells on MSC are depicted in black while those of MSC on immune cells are in red.*#*#*#*#*#MSC移植后24小时尿蛋白变化未治疗对照组 MSC移植组BDCAMSC移植对MRL/lpr鼠肾组织病理改变的影响A:对照组，B:CTX组，C

13、:MSC组，D:MSC+CTX组BACDMSC移植对MRL/lpr鼠肾小球补体C3沉积的影响异基因骨髓MSC移植治疗SLE女，女，21岁，岁，SLE13SLE13年，年，尿蛋白尿蛋白3+，血，血Cr477umol/L，P20mg/d,CTX 2P20mg/d,CTX 2年年(20(20克克),Cellcept 6months,),Cellcept 6months,BP160-180/100-120mmgBP160-180/100-120mmgHb 60g/LHb 60g/L 00.10.20.30.40.50.6移植前移植后2周C3C424小时尿蛋白定量（g）00.511.52移植前移植后2周24小时尿蛋白定量（g）474447430440450460470480移植前移植后2周Cr（umol/L）48.126.70102030405060移植前移植后2周Bun（mmol/L）异基因骨髓MSC移植治疗SLELN治疗IndividualMornitoringFellowupEducationAim at good quality of life!Thank you!66谢谢！谢谢！