KDIGO2024版狼疮肾炎治疗临床实践指南（附表）.docx

KDIGO2024版狼疮肾炎治疗临床实践指南（附表）2021年,改善全球肾脏病预后组织（KDIGO）发布了肾小球疾病治疗临床实践指南，其中包括了狼疮肾炎（LN）。2024年1月3日，KDIGO发布了最新的LN治疗临床实践指南，本次更新考虑了自2022年2月以来发表的随机对照研究的证据。本次更新包括了LN的诊断、治疗和特殊情况。1.N的诊断1.N诊断的方法如图1所示。Patient With ytemc lupus erythematosusTesting indicated when: Systemic lupus erythematosus presentation AS regular SurveiIUnce Suspicion of disease fUre Testing panel： Sewm creatinine and e<SFR Urinalysis (dpstkk and sediment) Spot prote<n-<reat*Me rat> (PCR) Serotogy (ant>dsONA and COmPiemenUIs there evidence OfabOOanal proteinuria <x urine sediment Abnormal proceinurla assessed by dipstdc protein 24(any level of specific gravity), dipstkk protein 1 OoW specifk gravity), or spot PCR >500 mg/g (50 mg/mmol) Urine sediment positive for canttmytes(25%). red blood cell casts or white Uood Cei castsIIs there evidence of decreased OC decreasing GPU Foc example abnormal KFR that is MoW theexpected level based on age and dlnkal history,or decreasing eGFR. with no attributablecause other than systemic lupus erythematosusNoNo further urinetesting at this timeQuantify proteinuriaNo further kidney functiontesting at this timeRepeat testingb24-ourPrOteinUrU2500mg/d?NoRepeattestingandfollowtheprogressConsicfor kidney biopsyNofurtherurinetestingatthistime治疗1 .除非有禁忌症，所有系统性狼疮（SLE）以及LN患者都应接受羟氯噬的治疗（1C）。2 .应该考虑对LN进行管理，减轻LN疾病或其并发症:心血管疾病风险：生活方式管理，如减重、加强锻炼、戒烟等；血脂管理；孕期接受小剂量阿司匹林管理；血压管理。蛋白尿与慢性肾脏病（CKD）:避免高钠饮食；血压管理；肾脏保护作用的药物,如肾素血管紧张素醛固酮系统阻滞剂（RAASi）.钠葡萄糖共转运蛋白2抑制剂SGLT-2i繇避免肾毒性药物预防急性肾损伤AKI%感染风险评估带状疱疹和肺结核病史；筛查HBVxHCV、HIV和HBV,并接种相关疫苗；预防乙肝肺囊虫；个体化评估流感及肺炎球菌疫苗重组带状疱疹疫苗的接种事宜；在考虑接种时，除了考虑个体情况，还应考虑公共卫生的状况。骨损伤：SLE以及LN患者应接受骨密度与骨折风险评估；个体化补充钙与维生素D以及使用双磷酸盐。紫外线照射：全身防晒霜涂抹、限制紫外线照射。卵巢早衰：促性腺激素释放激素激动剂；精子/卵母细胞冷冻。非计划妊娠：避孕咨询。癌症：个体评估癌症发生风险；年龄特异性肿瘤筛查；减少环磷酰胺的暴露（36g）o3.I/II型LN的治疗路径(图2)KidneybiopsyshowingClassl/lllupusnephritisLow-levelproteinuriaNephroticsyndromeEvaluateforlupuspodocytopathy(electronmicroscopywouldbeuseful)Treatasminimalchangedisease(Chapter5)Immunosuppressive treatmentguided by extra renal manifestationsof systemic lupus erythematosusConsider maintenance combinationtherapy with low-dose glucocorticoidand another immunosuppressive agent图2I/II型LN的治疗路径图4.III/IV型LN的治疗应在糖皮质激素的基础上加用以下任意1种治疗方案：霉酚酸类似物(MPAA)(IB);低剂量静注环磷酰胺(1B);贝利尤单抗+MPAA或低剂量静注环磷酰胺(1B);当患者肾功能未显著受损(定义：估算肾小球滤过率eGFR45mlmin1.73f)0寸,可使用MPAA+钙调神经磷酸酶抑制剂(CNI)(IB)。5.在活动性LN的初始治疗中,当肾脏和肾外疾病表现均显示满意改善时,可考虑在短疗程甲泼尼龙冲击后使用减量糖皮质激素(图3)。High-doseschemeModerate-doseschemeReduced-doseschemeMethylprednisoloneintravenouspulsesNilor0.25-05g/dayupto3daysasinitialtreatment0.25-0.5g/dayupto3daysoftenindudedasinitialtreatment025-0.5g/dayupto3daysusuallyindudedasinitialtreatmentOralprednisoneequivalent(/day)Week0-2Week3-4Week5-6Week7-8Week9-10Week11-12Week13-14Week15-16Week17-18Week19-20Week21-24Week>2501.0mg/kg(max80mg)0.6-07mg/kg30mg25mg20mg15mg12.5mgIOmg75mg75mg5mg<5mg0.6-0.7mg/kg(max50mg)05-0.6mg/kg20mgISmg125mgIOmg7.5mg7.5mgSmg5mg<5mg<5mg05-0.6mg/kg(max40mg)03-0.4mg/kg15mgIOmg75mg5mg25mg25mg25mg23mg25mg<25mg图3减量糖皮质激素的用法与用量6.完成起始治疗后，LN患者应接受MPAA的维持性治疗（1B）,不耐受.无法获得MPAA或考虑妊娠者，可选用硫理噤吟；维持期糖皮质激素应减量至最低剂量，但肾外SLE表现需要使用糖皮质激素时除外;在患者的肾脏临床完全缓解维持12个月后，可考虑停用糖皮质激素，具体维持期药物的联用方法参照图4oMaintenanceimmuno-suppressiveregimensLow-doseglucocorticoidsANDMycophenolkaddanalogsAzathiopnntBdimumabandmycophenolicaddanalogsorazathiopnneCNIandmycophenolkaddanalogsCNI(suchasvodosporirtacrolimusorQfclosporine)MinbinCommentsPreferredtreatmentbasedonhigh-certaintyevidencelowerflareratethanazathioprinemaintenanceLowmedicationcost;safeinpregnancyEfficacyandsafetyofbe*mumabdemonstratedinBLtSS-LN(KMrk)andopen4abdextensiontrials(28三wk)PracticePoint102.323)EffiocyandsafetyofvodospocindemonstratedinAURORA1(S2wk)>ndAURORA2continuationtrials(2-y);efficacyandsafetyoftaolimusdemonstratedin4MuItitargHTherap/trialinChinesepatientsinwhichtacrolimusandreduced-doseMMAweregivenfor24monthsPractkePoint102323)TdCfoIirmisandCydosporinesafeknpregnancy；insufdentpregnancydataonVodOSPOrinExperiencemostlyinJapanesepatients图4III/IVLN维持期的药物联用方法7.V型LN患者的治疗方案参见图5KidneybiopsyshowingClassVlupusnephritis1Renin-angiotensinsystemblockadeandbloodpressurecontrol2Immunosuppressivetreatmentguidedbyextrarenalmanifestationsofsystemklupuserythematosus3Hydroxychloroquine1Renin-angiotensinsystemblockadeandbloodpressurecontrol2Combinedimmunosuppressivetreatmentwithglucocorticoidandoneotheragent(e.g.,mycophenolicacidanalogs,cyclophosphamide,Cakineurininhibitorrituximab,azathk)prine).Insufficientdataforrecommendationofglucocorticoidregimen,butmoderateorreduceddosePreferred.PleaserefertoPracticePoint1023.1.1.3HydroxychloroquineIfproteinuriaworsensand/orcomplicationsofproteinuriadevelop(e.g.thrombosis,dyslipidemia,edema),considerimmunosuppressivetherapy图5V型LN患者的治疗方案8.LN患者对治疗的反应可分为完全缓解（CR）、主要肾脏反应（Primaryefficacyrenalresponse）、部分缓解（PR）和无肾脏反应，其定义如下图（图6）所示。CriteriaDefinitionCompleteresponse* Reductioninproteinuria<0,5g/g(50mg/mmol)measuredasthePCRfroma24-hurinecollection Stabilizationorimprovementinkidneyfunction仕10%-15%ofbaseline) Within6-12moofstartingtherapy,butcouldtakemorethan12moPrimaryefficacyrenalresponse PCR0.7g/g(70mg/mmol) eGFRthatwasnoworsethan20%belowthepreflarevalueor60ml/minper1.73m2 NouseofrescuetherapyfortreatmentfailurePartialresponse Reductioninproteinuriabyatleast50%andto<3g/g(300mg/mmol)measuredasthePCRfroma24-hurinecollection Stabilizationorimprovementinkidneyfunction(±10%-15%ofbaseline) Within6-12moofstartingthe、pyNokidneyresponseFailuretoachieveapartialorcompleteresponsewithin6-12moofstartingtherapy特殊情况1 .当疗效不令人满意时应根据患者的情况进行5步管理法，具体管理方法如下：核实依从性；通过实验室检查，明确免疫抑制药物的血药浓度，调整剂量；如果合并或怀疑患者有其他慢病（如血栓性微血管病TMA）,则应重复肾活检；当出现持续性活动性疾病时，考虑转换为推荐的替代治疗方案；对于一线治疗方案的难治性患者，应考虑以下治疗方案：加用利妥昔单抗或其他生物制剂；延长静脉注射环磷酰胺的疗程；符合条件的情况下建议患者加入临床试验。2 .治疗LN复发在达到完全或部分缓解后，LN复发应采用与达到最初应答相同的初始治疗，或采用推荐的替代治疗。3 .合并TMA的LN患者合并TMA的LN患者，其治疗方式需要特别注意，可参考下图（图7）。1.upusnephritisANDsuspectedthromboticmicroangiopathy图7合并TMA的LN患者治疗路径图4 .怀孕的LN患者LN患者应在LN活动期间、接受可能致畸药物治疗时，以及LN转为非活动后6个月内避免妊娠。为降低妊娠并发症的风险，妊娠期间应继续使用羟氯喽，并在妊娠16周前开始使用小剂量阿司匹林。糖皮质激素、羟氯瞳、硫嘤瞟岭、他克莫司和环泡素被认为是妊娠期安全的免疫抑制治疗。5 .儿童LN患者使用与成人相似的免疫抑制方案治疗儿童LN患者，但在制定治疗计划时要考虑与该人群相关的问题,如剂量调整、生长、生育和心理社会因素。发生肾功能衰竭的儿童LN患者可接受血液透析、腹膜透析或肾移植治疗;肾移植优于长期透析。参考文献：1.KidneyDisease:ImprovingGlobalOutcomes(KDIGO)LupusNephritisWorkGroup.KDIGO2024ClinicalPracticeGuidelineforthemanagementofLUPUSNEPHRITIS.KidneyInt2024Jan;105(1S):S1-S69.