CAJ | 학술논문

目的探讨他克莫司(TAC)治疗儿童难治性肾病综合征的临床疗效.方法选择2010年1月至2013年12月在南京军区南京总医院儿科住院的难治性肾病综合征患儿191例,其中激素依赖型101例、激素耐药型73例、频繁复发型17例.每例患儿均使用TAC,在用药过程中监测TAC血药浓度,并根据不同情况减量使用糖皮质激素及停用相关其他免疫抑制剂.分别于治疗前和治疗4周、8周观察相关临床和实验室检测指标的变化.结果 191例患儿经TAC治疗8周后总缓解率达86.9％(166/191例),最早显效时间6d,治疗后血浆清蛋白、血脂等临床生化指标明显改善,差异均有统计学意义(P均＜0.01),蛋白尿明显减轻(t=20.14,P＜0.01).191例中有115例行肾活检,其中微小病变型(MCN)疗效最好,缓解率达90.5％(19/21例),其次为系膜增生性肾小球肾炎(MsPGS),缓解率达87.7％(57/65例),局灶节段性硬化(FSGS)、膜性肾病(MN)、膜增生性肾小球肾炎(MPGN)也有不同程度缓解.本组病例有32例测定TAC药物代谢基因型P450Cyp3A5,3/3型和1/3型合并在一起总缓解率为75.0％(21/28例),而4例1/1型治疗4周无一例缓解.本组病例治疗过程中不良反应较少,多为轻微消化道症状、一过性肾功能损害、血糖异常、头痛、烦躁及肢体疼痛等,不影响治疗进程.结论针对儿童难治性肾病综合征的治疗,TAC是一种不良反应少、有临床疗效的强效免疫抑制剂,有着良好的应用前景.
목적 탐토타극막사(TAC)치료인동난치성신병종합정적림상료효.방법 선택2010년1월지2013년12월재남경군구남경총의원인과주원적난치성신병종합정환인191례,기중격소의뢰형101례、격소내약형73례、빈번복발형17례.매례환인균사용TAC,재용약과정중감측TAC혈약농도,병근거불동정황감량사용당피질격소급정용상관기타면역억제제.분별우치료전화치료4주、8주관찰상관림상화실험실검측지표적변화.결과 191례환인경TAC치료8주후총완해솔체86.9％(166/191례),최조현효시간6d,치료후혈장청단백、혈지등림상생화지표명현개선,차이균유통계학의의(P균＜0.01),단백뇨명현감경(t=20.14,P＜0.01).191례중유115례행신활검,기중미소병변형(MCN)료효최호,완해솔체90.5％(19/21례),기차위계막증생성신소구신염(MsPGS),완해솔체87.7％(57/65례),국조절단성경화(FSGS)、막성신병(MN)、막증생성신소구신염(MPGN)야유불동정도완해.본조병례유32례측정TAC약물대사기인형P450Cyp3A5,3/3형화1/3형합병재일기총완해솔위75.0％(21/28례),이4례1/1형치료4주무일례완해.본조병례치료과정중불량반응교소,다위경미소화도증상、일과성신공능손해、혈당이상、두통、번조급지체동통등,불영향치료진정.결론 침대인동난치성신병종합정적치료,TAC시일충불량반응소、유림상료효적강효면역억제제,유착량호적응용전경.
Objective To explore the clinical effect of Tacrolimus in pediatric refractory nephrotic syndrome.Methods One hundred and ninety-one children with refractory nephrotic syndrome in Nanjing General Hospital of Nanjing Military Region,People's Liberation Army,were enrolled from January 2010 to December 2013,including 101 cases of steroid-dependent nephrotic syndrome,73 cases of steroid-dependent nephrotic syndrome,and 17 cases of frequently relapsing nephrotic syndrome.Tacrolimus was applied to all the patients.The plasma concentrations of Tacrolimus during the treatment were measured and glucocorticoid tapered or some other immunosuppressants discontinued based on clinical judgment.Relevant clinical changes and laboratory test values were observed before treatment and in weeks 4,8 after treatment.Results The overall remission rate was 86.9％ (166/191 cases) after 8 weeks treatment of Tacrolimus.The minimum effective time was 6 days.Serum albumin and cholesterol significantly improved (all P ＜ 0.01),and proteinuria also diminished markedly(t =20.14,P ＜0.01).One hundred and fifteen patients underwent renal biopsy.The treatment with Tacrolimus did well in minimal change nephropathy(MCN) [remission rate was 90.5％ (18/21 cases)],but mesangial proliferative glomerulonephritis(MsPGS) was inferior in its efficacy(87.7％) (57/65 cases).The use of Tacrolimus in focal segmental glomerulosclerosis (FSGS),membranous nephropathy (MN) and membranoproliferative glomerulonephritis(MPGN) also produced remission to some extent.Thirty-two cases were analyzed by way of Tacrolimus metabolic genotype.The remission rate of 3/3 or 1/3 Tacrolimus metabolic genotype was 75.0％ (21/28 cases),but 4 cases with 1/1 tacrolimus metabolic genotype did not remit after 4 weeks treatment.The adverse reactions of tacrolimus were mild,mainly slight digest tract symptoms,transient kidney injury,dysglycemia,headache,dysphoria etc,which did not influence the treatment.Conclusions Tacrolimus has a gold application prospect,and is a powerfully effective immunosuppressant with clinical efficacy and less side effects for refractory nephritic syndrome in children.