背景:环孢素A的应用显著提高了移植肾的早期存活率,但远期移植物失功并未得到明显改善.他克莫司能否延缓慢性移植肾肾病进展,从而延长移植物的存活时间?目的:观察他克莫司替换环孢素A治疗慢性移植肾肾病的有效性及安全性.设计:观察对比实验.单位:中南大学湘雅二医院器官移植中心泌外器官移植科.对象:选择2001-04/2005-10在中南大学湘雅二医院器官移植中心泌外器官移植科接受同种异体肾移植术后发生慢性移植肾肾病的73例患者,均经移植肾穿刺活检证实.男42例,女31例,年龄19～69岁,所有患者均对治疗项目知情同意,实验经过医院伦理委员会批准许可.环孢素A软胶囊为杭州中美华东制药有限公司或华北制药有限公司产品,吗替麦考酚酸酯胶囊购自上海罗氏制药有限公司,醋酸泼尼松片为中南大学湘雅二医院提供,他克莫司胶囊为藤泽药品中国有限公司产品.方法:根据患者治疗意愿将患者分为环孢素A组(n =30)和他克莫司组(n =43),两组患者性别、年龄及一般情况差异无统计学意义(P > 0.05).环孢素A组患者维持原免疫抑制方案进行治疗,即环孢素A、霉酚酸酯及泼尼松联用.他克莫司组将环孢素A转换成他克莫司, 他克莫司转换方案为停服环孢素A 24 h后开始服用他克莫司,其起始剂量为0.08～0.1 mg/(kg·d),早晚餐后2 h口服,服药3 d后测其谷值浓度,要求其血药浓度维持在5～8μg/L,并根据血药浓度、血清肌酐及其毒副作用调整剂量,其他用药同环孢素A组,两组均治疗12个月. 主要观察指标:①治疗12个月后监测两组患者血清肌酐、肾小球滤过率、24 h尿蛋白定量、血脂(包括总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇等生化指标)变化情况;②观察药物毒副作用(震颤、高血糖及高血压等发生情况).结果:患者73例均进入结果分析.①生化指标检测结果:转换治疗12个月后,他克莫司组血清肌酐及24 h尿蛋白定量显著低于环孢素A组,差异有统计学意义(P < 0.01);肾小球滤过率显著高于环孢素A组,差异有统计学意义(P < 0.01);总胆固醇、三酰甘油、低密度脂蛋白胆固醇均显著低于环孢素A组,差异有统计学意义(P < 0.01).②毒副作用:他克莫司组震颤发生率为,高于环孢素A组[30% (9/30),5%(2/43),(P < 0.01)],差异有显著性意义,高血压发生率为,显著低于环孢素A组[56%(24/43),83%,(25/30),(P < 0.05)],差异有显著性意义.结论:他克莫司转换治疗后,肾功能减退得到延缓,蛋白尿减少,血脂代谢得到改善,他克莫司可以有效延缓慢性移植肾肾病进展.
揹景:環孢素A的應用顯著提高瞭移植腎的早期存活率,但遠期移植物失功併未得到明顯改善.他剋莫司能否延緩慢性移植腎腎病進展,從而延長移植物的存活時間?目的:觀察他剋莫司替換環孢素A治療慢性移植腎腎病的有效性及安全性.設計:觀察對比實驗.單位:中南大學湘雅二醫院器官移植中心泌外器官移植科.對象:選擇2001-04/2005-10在中南大學湘雅二醫院器官移植中心泌外器官移植科接受同種異體腎移植術後髮生慢性移植腎腎病的73例患者,均經移植腎穿刺活檢證實.男42例,女31例,年齡19～69歲,所有患者均對治療項目知情同意,實驗經過醫院倫理委員會批準許可.環孢素A軟膠囊為杭州中美華東製藥有限公司或華北製藥有限公司產品,嗎替麥攷酚痠酯膠囊購自上海囉氏製藥有限公司,醋痠潑尼鬆片為中南大學湘雅二醫院提供,他剋莫司膠囊為籐澤藥品中國有限公司產品.方法:根據患者治療意願將患者分為環孢素A組(n =30)和他剋莫司組(n =43),兩組患者性彆、年齡及一般情況差異無統計學意義(P > 0.05).環孢素A組患者維持原免疫抑製方案進行治療,即環孢素A、黴酚痠酯及潑尼鬆聯用.他剋莫司組將環孢素A轉換成他剋莫司, 他剋莫司轉換方案為停服環孢素A 24 h後開始服用他剋莫司,其起始劑量為0.08～0.1 mg/(kg·d),早晚餐後2 h口服,服藥3 d後測其穀值濃度,要求其血藥濃度維持在5～8μg/L,併根據血藥濃度、血清肌酐及其毒副作用調整劑量,其他用藥同環孢素A組,兩組均治療12箇月. 主要觀察指標:①治療12箇月後鑑測兩組患者血清肌酐、腎小毬濾過率、24 h尿蛋白定量、血脂(包括總膽固醇、三酰甘油、低密度脂蛋白膽固醇、高密度脂蛋白膽固醇等生化指標)變化情況;②觀察藥物毒副作用(震顫、高血糖及高血壓等髮生情況).結果:患者73例均進入結果分析.①生化指標檢測結果:轉換治療12箇月後,他剋莫司組血清肌酐及24 h尿蛋白定量顯著低于環孢素A組,差異有統計學意義(P < 0.01);腎小毬濾過率顯著高于環孢素A組,差異有統計學意義(P < 0.01);總膽固醇、三酰甘油、低密度脂蛋白膽固醇均顯著低于環孢素A組,差異有統計學意義(P < 0.01).②毒副作用:他剋莫司組震顫髮生率為,高于環孢素A組[30% (9/30),5%(2/43),(P < 0.01)],差異有顯著性意義,高血壓髮生率為,顯著低于環孢素A組[56%(24/43),83%,(25/30),(P < 0.05)],差異有顯著性意義.結論:他剋莫司轉換治療後,腎功能減退得到延緩,蛋白尿減少,血脂代謝得到改善,他剋莫司可以有效延緩慢性移植腎腎病進展.
배경:배포소A적응용현저제고료이식신적조기존활솔,단원기이식물실공병미득도명현개선.타극막사능부연완만성이식신신병진전,종이연장이식물적존활시간?목적:관찰타극막사체환배포소A치료만성이식신신병적유효성급안전성.설계:관찰대비실험.단위:중남대학상아이의원기관이식중심비외기관이식과.대상:선택2001-04/2005-10재중남대학상아이의원기관이식중심비외기관이식과접수동충이체신이식술후발생만성이식신신병적73례환자,균경이식신천자활검증실.남42례,녀31례,년령19～69세,소유환자균대치료항목지정동의,실험경과의원윤리위원회비준허가.배포소A연효낭위항주중미화동제약유한공사혹화북제약유한공사산품,마체맥고분산지효낭구자상해라씨제약유한공사,작산발니송편위중남대학상아이의원제공,타극막사효낭위등택약품중국유한공사산품.방법:근거환자치료의원장환자분위배포소A조(n =30)화타극막사조(n =43),량조환자성별、년령급일반정황차이무통계학의의(P > 0.05).배포소A조환자유지원면역억제방안진행치료,즉배포소A、매분산지급발니송련용.타극막사조장배포소A전환성타극막사, 타극막사전환방안위정복배포소A 24 h후개시복용타극막사,기기시제량위0.08～0.1 mg/(kg·d),조만찬후2 h구복,복약3 d후측기곡치농도,요구기혈약농도유지재5～8μg/L,병근거혈약농도、혈청기항급기독부작용조정제량,기타용약동배포소A조,량조균치료12개월. 주요관찰지표:①치료12개월후감측량조환자혈청기항、신소구려과솔、24 h뇨단백정량、혈지(포괄총담고순、삼선감유、저밀도지단백담고순、고밀도지단백담고순등생화지표)변화정황;②관찰약물독부작용(진전、고혈당급고혈압등발생정황).결과:환자73례균진입결과분석.①생화지표검측결과:전환치료12개월후,타극막사조혈청기항급24 h뇨단백정량현저저우배포소A조,차이유통계학의의(P < 0.01);신소구려과솔현저고우배포소A조,차이유통계학의의(P < 0.01);총담고순、삼선감유、저밀도지단백담고순균현저저우배포소A조,차이유통계학의의(P < 0.01).②독부작용:타극막사조진전발생솔위,고우배포소A조[30% (9/30),5%(2/43),(P < 0.01)],차이유현저성의의,고혈압발생솔위,현저저우배포소A조[56%(24/43),83%,(25/30),(P < 0.05)],차이유현저성의의.결론:타극막사전환치료후,신공능감퇴득도연완,단백뇨감소,혈지대사득도개선,타극막사가이유효연완만성이식신신병진전.
BACKGROUND: The introduction of cyclosporin A (CsA) has greatly enhanced the early survival rate of kidney graft, but the long-term graft survival rate is still limited. Whether tacrolimus prevents chronic allograft nephropathy (CAN) and prolongs survival time is now becoming a hot spot in field of renal transplantation.OBJECTIVE: To investigate the feasibility and safety of converting CsA to tacrolimus (FK506) in preventing progression of CAN. DESIGN: Observation and controlled trial.SETTING: Department of Urological Organ Transplantation, Center of Organ Transplantation, the Second Xiangya Hospital, Central South University.PARTICIPANTS: A total of 73 patients who had received kidney transplantation at the Department of Urological Organ Transplantation, Center of Organ Transplantation, the Second Xiangya Hospital of Central South University from April 2001 to October 2005, and had been diagnosed as CAN by graft biopsy (42 male patients and 31 female patients; age ranged 19-69 years), were enrolled in the study approved by the ethics committee of this hospital after their written informed consents. CsA soft capsules (Hangzhou Zhongmei Huadong Pharmaceutical Limited Company or Huabei Pharmaceutical Limited Company); mycophenolate mofetil capsules (Shanghai Roche Pharmaceutical Limited Company); prednisone acetate tablets (Second Xiangya Hospital of Central South University); tacrolimus capsules (Fujisawa Pharmaceutical Limited Company).METHODS: Seventy-three patients voluntarily participated in CsA group (n =30) or FK506 group (n =43). The two groups were homogenous regarding patients' sex, age and general data (P > 0.05). Patients in the CsA group were continued on their initial immunosuppression protocol, which consisted of CsA, mycophenolate mofetil and prednisone acetate. In the FK506 group, CsA was stopped, and FK506 was started at a dose of 0.08-0.1 mg/(kg·d) 24 hours later, twice daily, administered 2 hours after breakfast and supper. Three days later, the blood trough concentration of FK506 was tested and adjusted to a target range of 5-8μg/L. FK506 dosage adjustment was based on the blood trough concentration, serum creatinine (SCr) and its side effects. All 73 patients were treated for 12 months. MAIN OUTCOME MEASURES: SCr, glomerular filtration rate (GFR), 24-hour urine protein excretion, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL) and the toxic side effects of calcineurin inhibitors (incidences of tremor, hyperglycemia and hypertension) were monitored during a follow-up of over 12 months. RESULTS: A total of 73 patients were involved in the result analysis.①12 months after conversion, the level of SCr was statistically reduced and GFR levels were markedly elevated in the FK506 group compared with the CsA group (P < 0.01). TC, TG and LDL levels in the FK506 group were significantly lower than those in the CsA group (P < 0.01).②Compared with the CsA group, the incidence of tremor was obviously increased [30% (9/30), 5% (2/43), P < 0.01] and the incidence of hypertension was obviously decreased [56% (24/43), 83% (25/30), P < 0.05] in the FK506 group.CONCLUSION: Conversion from CsA to FK506 can postpone renal dysfunction, reduce proteinuria and improve hyperlipidemia. FK506 treatment is an effective therapy in slowing the progression of CAN.
