CAJ | 학술논문

目的：针对抗中性粒细胞细胞质抗体（ anti-neutrophil cytoplasmic antibodies， ANCA）相关性血管炎（ ANCA asso-ciated vasculitis， AAV）的治疗方案如激素联合环磷酰胺或吗替麦考酚酯（ mycophenolate mofetil， MMF）虽可提高治疗缓解率，但复发率及治疗相关的不良反应发生率高。文中回顾性观察多靶点疗法治疗AAV肾损害患者的临床疗效与安全性。方法回顾性收集2009年6月至2013年10月间在南京军区南京总医院诊断为AAV，伴有肾损害，血肌酐（ serum creatinine， SCr）≤3 mg／dL，并采用多靶点疗法治疗的患者7例，其中男性1例、女性6例，年龄21～54岁，均为髓过氧化物酶-ANCA（ myeloperoxi-dase-ANCA， MPO-ANCA）阳性，均有大量尿蛋白和血尿。其中4例SCr升高（1．47～2．94 mg／dL）伴eGFR＜60 mL／min，3例SCr正常（其中2例eGFR＞90 mL／min、1例eGFR＜90 mL／min）。肾活检病理类型包括混合型（5例）和新月体型（2例）。均给予激素联合MMF（0．5～0．75 g／d）和FK506（1．5～3 mg／d）治疗，观察多靶点治疗的临床疗效和不良反应。结果所有患者多靶点治疗6～24个月（中位时间12个月），随访12～53个月（中位时间46个月）。诱导期MMF剂量0．5～0．75 g／d，FK506剂量1．5～3 mg／d。诱导治疗期间7例患者均获得完全缓解。治疗6个月伯明翰血管炎活动性评分（ Birmingham vasculitis ac-tivity score， BVAS）均下降至0分，无活动性尿沉渣，6例尿蛋白转阴；治疗前4例eGFR＜60 mL／min者中1例eGFR恢复正常，另3例升高至64．8～87．4 mL／min，eGFR＞60 mL／min的3例eGFR均恢复正常。随访末，4例eGFR正常，1例eGFR 介于60～90 mL／min之间，2例eGFR＜60 mL／min，无终末期肾病发生。3例血清MPO-ANCA转阴，4例MPO-ANCA水平明显下降。随访期间无严重不良反应，无复发及死亡。结论多靶点疗法可有效控制伴轻中度肾功能损害AAV患者的肾活动，显著改善肾功能和尿蛋白，耐受性良好，但其疗效仍需临床研究进一步验证。目的：針對抗中性粒細胞細胞質抗體（ anti-neutrophil cytoplasmic antibodies， ANCA）相關性血管炎（ ANCA asso-ciated vasculitis， AAV）的治療方案如激素聯閤環燐酰胺或嗎替麥攷酚酯（ mycophenolate mofetil， MMF）雖可提高治療緩解率，但複髮率及治療相關的不良反應髮生率高。文中迴顧性觀察多靶點療法治療AAV腎損害患者的臨床療效與安全性。方法迴顧性收集2009年6月至2013年10月間在南京軍區南京總醫院診斷為AAV，伴有腎損害，血肌酐（ serum creatinine， SCr）≤3 mg／dL，併採用多靶點療法治療的患者7例，其中男性1例、女性6例，年齡21～54歲，均為髓過氧化物酶-ANCA（ myeloperoxi-dase-ANCA， MPO-ANCA）暘性，均有大量尿蛋白和血尿。其中4例SCr升高（1．47～2．94 mg／dL）伴eGFR＜60 mL／min，3例SCr正常（其中2例eGFR＞90 mL／min、1例eGFR＜90 mL／min）。腎活檢病理類型包括混閤型（5例）和新月體型（2例）。均給予激素聯閤MMF（0．5～0．75 g／d）和FK506（1．5～3 mg／d）治療，觀察多靶點治療的臨床療效和不良反應。結果所有患者多靶點治療6～24箇月（中位時間12箇月），隨訪12～53箇月（中位時間46箇月）。誘導期MMF劑量0．5～0．75 g／d，FK506劑量1．5～3 mg／d。誘導治療期間7例患者均穫得完全緩解。治療6箇月伯明翰血管炎活動性評分（ Birmingham vasculitis ac-tivity score， BVAS）均下降至0分，無活動性尿沉渣，6例尿蛋白轉陰；治療前4例eGFR＜60 mL／min者中1例eGFR恢複正常，另3例升高至64．8～87．4 mL／min，eGFR＞60 mL／min的3例eGFR均恢複正常。隨訪末，4例eGFR正常，1例eGFR 介于60～90 mL／min之間，2例eGFR＜60 mL／min，無終末期腎病髮生。3例血清MPO-ANCA轉陰，4例MPO-ANCA水平明顯下降。隨訪期間無嚴重不良反應，無複髮及死亡。結論多靶點療法可有效控製伴輕中度腎功能損害AAV患者的腎活動，顯著改善腎功能和尿蛋白，耐受性良好，但其療效仍需臨床研究進一步驗證。
목적：침대항중성립세포세포질항체（ anti-neutrophil cytoplasmic antibodies， ANCA）상관성혈관염（ ANCA asso-ciated vasculitis， AAV）적치료방안여격소연합배린선알혹마체맥고분지（ mycophenolate mofetil， MMF）수가제고치료완해솔，단복발솔급치료상관적불량반응발생솔고。문중회고성관찰다파점요법치료AAV신손해환자적림상료효여안전성。방법회고성수집2009년6월지2013년10월간재남경군구남경총의원진단위AAV，반유신손해，혈기항（ serum creatinine， SCr）≤3 mg／dL，병채용다파점요법치료적환자7례，기중남성1례、녀성6례，년령21～54세，균위수과양화물매-ANCA（ myeloperoxi-dase-ANCA， MPO-ANCA）양성，균유대량뇨단백화혈뇨。기중4례SCr승고（1．47～2．94 mg／dL）반eGFR＜60 mL／min，3례SCr정상（기중2례eGFR＞90 mL／min、1례eGFR＜90 mL／min）。신활검병리류형포괄혼합형（5례）화신월체형（2례）。균급여격소연합MMF（0．5～0．75 g／d）화FK506（1．5～3 mg／d）치료，관찰다파점치료적림상료효화불량반응。결과소유환자다파점치료6～24개월（중위시간12개월），수방12～53개월（중위시간46개월）。유도기MMF제량0．5～0．75 g／d，FK506제량1．5～3 mg／d。유도치료기간7례환자균획득완전완해。치료6개월백명한혈관염활동성평분（ Birmingham vasculitis ac-tivity score， BVAS）균하강지0분，무활동성뇨침사，6례뇨단백전음；치료전4례eGFR＜60 mL／min자중1례eGFR회복정상，령3례승고지64．8～87．4 mL／min，eGFR＞60 mL／min적3례eGFR균회복정상。수방말，4례eGFR정상，1례eGFR 개우60～90 mL／min지간，2례eGFR＜60 mL／min，무종말기신병발생。3례혈청MPO-ANCA전음，4례MPO-ANCA수평명현하강。수방기간무엄중불량반응，무복발급사망。결론다파점요법가유효공제반경중도신공능손해AAV환자적신활동，현저개선신공능화뇨단백，내수성량호，단기료효잉수림상연구진일보험증。
Objective The treatment of anti-neutrophil cytoplasmic antibodies ( ANCA) associated vasculitis ( AVV) such as mycophenolate mofetil ( MMF ) can improve the remission rate, however, it also results in high recurrence rate and high incidence of adverse reaction related to the treatment.The article was to observe the clinical efficacy and safety of multi-target therapy ( MT ) in the treatment of AAV with renal involvement. Methods Retrospective observation was made on 7 AVV patients treated with multi-target therapy in our department from June 2009 to October 2013.The pa-tients (1 male, 6 females) aged from 21 to 54 years were accompa-nied with renal damage and serum creatinine (SCr≤3 mg/dL).All patients had positive myelopeeroxidase-ANCA (MPO-ANCA), high-grade proteinuria and hematuria.4 patients had elevated SCr (1.47-2.94 mg/dL) with EGFR<60 mL/min, 3 patients had normal SCr ( EGFR>90 mL/min in 2 patients and EGFR<90mL/min in 1 patient) .The renal histological classification included focal type (n=5) and crescentic type (n=2).All patients received MT therapy which was composed with the steroids, MMF (0.5-0.75g/d) and FK506 (1.5-3 mg/d).The remission rate, the change of renal function, proteinuria and ANCA, adverse reaction and relapse were investigated. Results The patients had received MT for 6 to 24 months ( median 12 m) and had been followed up for 9 to 53 months ( median 46 m).All patients achieved remission during MT induction treatment.The Birmingham vasculitis activity score (BVAS) decreased from 14 (6~16) to 0, without urinary sediment, and complete remission of proteinuria was found in 6 patients. Before the therapy the EGFR expression was normal in 1 patient and 64.8-87.4 mL/min in 3 patients among 4 patients (EGFR<60 mL/min) , and the EGFR expression became normal in 3 patients ( EGFR>60 mL/min) .At the end of follow-up, the EGFR expres-sion was normal in 4 patients, 60-90 mL/min in 1 patient and less than 60 mL/min in 2 patients, without end stage renal disease. ANCA level turned to normal in 3 patients and significantly decreased in 4 patients.No patients had adverse reaction, died, or re-lapsed during the follow-up. Conclusion MT is effective in the control of renal activities of AVV patients with mild or moderate re-nal function damage.It attributes to great improvement of renal function and urine protein, as well as good tolerance.However, pro-spective study is required to confirm the efficacy of this new therapy.