儿童微小病变型肾病综合征免疫学机制研究进展

微小病变型肾病综合征(MCNS)是儿童原发性肾病综合征(INS)最常见的病理类型.MCNS发病机制尚不清楚.既往认为MCNS发病与T细胞功能紊乱有关,此外,细胞因子、B细胞、足细胞及Toll样受体(TLRs)亦可能参与MCNS发病过程.本文就MCNS发病机制中免疫学方面的进展加以综述.     

呼吸道病毒诱发的微小病变型肾病综合征发病机制的研究进展

微小病变型肾病综合征(Minimal changed nephrotic syndrome,MCNS)是肾病综合征常见的病理组织类型,儿童发病率高,其发病机制尚未完全明确。近年发现,MCNS的发病具有遗传基础,T淋巴细胞异常参与本病的发病。笔者主要从病毒诱发具有遗传易感素质的机体后引起本病的发病机制进行综述。     

单用他克莫司治疗微小病变性肾病综合征的临床研究

目的探讨单用他克莫司治疗微小病变性肾病综合征的疗效和安全性。方法选取42名病理为微小病变的肾病综合征患者,随机分成强的松组和他克莫司组,他克莫司组采用口服他克莫司胶囊,使患者前24周他克莫司谷浓度维持在5~8ng.mL-1,后24周维持在3~6ng.mL-1。强的松组口服强的松片,强的松起始剂量为1mg/(Kg.d),8周后开始每周减少5mg,减至0.5mg/(Kg.d)时维持8周,再逐渐减至1日10mg维持到研究结束。两组疗程均为48周,观察两组的蛋白尿缓解率、血白蛋白、血脂水平及药物的副作用等。结果他克莫司组21例、强的松组20例完成研究,他克莫司组完全缓解率为95.24%,平均缓解时为2.35±0.67周,部分缓解率为4.76%。强的松组完全缓解率85%,平均缓解时间为2.61±0.78周,部分缓解率为15%。激素组向心性肥胖发生率为100%,痤疮发生率为45%,而他克莫司组却没有出现。两组在感染、血糖升高、血脂升高、转氨酶升高等方面的发生率相似。结论单用他克莫司治疗微小病变性肾病综合征疗效显著且安全性好。     

他克莫司联合小剂量激素治疗成人激素依赖或激素抵抗微小病变肾病的疗效

目的观察不同疗程中他克莫司治疗成人激素依赖或激素抵抗微小病变肾病的疗效和复发率。方法 2007年5月至2010年2月我院收治经皮肾活检诊断微小病变肾病,经糖皮质激素规律治疗表现为激素依赖或激素抵抗的26例病例,随机分为短疗程组12例和长疗程组14例。短疗程组给予他克莫司联合口服泼尼松治疗6个月,长疗程组治疗18个月,前6个月治疗同短疗程组,此后单用小剂量他克莫司维持,观察两组的疗效及复发等情况。结果短疗程组全部完成实验,治疗6个月后9例完全缓解,2例部分缓解,1例无效;治疗期间他克莫司的平均血药浓度保持在4～8μg/L;治疗过程中及观察结束时,6例复发。长疗程组治疗18个月后,9例获得完全缓解,2例获得部分缓解,1例无效,2例因严重不良反应退出研究,长疗程组他克莫司的浓度在6个月内波动于5～8μg/L,疗程结束时,2例复发。结论他克莫司是有效的诱导缓解药物,小剂量他克莫司维持治疗可以有效降低复发率。     

利妥昔单抗治疗激素和环磷酰胺抵抗的微小病变型肾病综合征达到长期完全缓解相关病例回顾和总结

本文报道1例患有微小病变型肾病综合征的20岁男性患者,初始激素治疗有效,但由于不遵医嘱突然自行停药后复发,并且出现激素和环磷酰胺抵抗,在使用利妥昔单抗2次后病情很快缓解,即使CD19细胞恢复,患者的完全缓解时间亦达到35个月。文献回顾和总结提示,在CD19细胞恢复后,利妥昔单抗仍然对部分儿童和成人的复发和难治性微小病变型肾病综合征有作用。     

金水宝联合甲泼尼龙治疗微小病变肾病的临床研究

目的 观察金水宝对糖皮质激素治疗微小病变肾病(MCD)临床效果.方法 选择2014年7月至2015年7月符合入选标准的初发MCD患者92例,随机分为治疗组与对照组,对照组予足量甲泼尼龙(0.8~1mg/(kg·d)),治疗组加用金水宝1次0.99,1日3次.结果 治疗组的疗效优于对照组(P<0.05):尿蛋白定量、血浆白蛋白、总胆固醇、甘油三酯等指标两组均显著改善,但治疗组为优;治疗组出现的阴虚火旺证侯积分值及副作用的发生率均较对照组低(P<0.05).结论 金水宝对激素治疗MCD起到增效减毒的作用,安全经济,值得临床推广.     

回顾性分析ACEI/ARB联用激素对微小病变型肾病综合征的影响

目的 研究血管紧张素转换酶抑制剂/血管紧张素受体拮抗剂(ACEI/ARB)联合激素治疗微小病型肾病综合征(MCD)的疗效.方法 回顾性分析1998年11月至2006年10月肾活检确诊为MCD的患者,分为激素单联用ACEI或ARB组、激素联用ACEI及ARB组,及单用激素组作为对照.结果 符合入组94例,激素单联用ACEI或ARB组(36例),复发率52.78%;激素联用ACEI及ARB组(30例),复发率56.67%;单用激素组(28例),复发率46.43%,其复发率及尿蛋白转阴时间均无统计学差异(P>0.05).结论 激素联用ACEI及或ARB不能降低MCD患者的复发率及缩短尿蛋白转阴时间.     

中性粒细胞/淋巴细胞比值对微小病变型肾病发生激素性骨坏死的预测价值

目的　探讨中性粒细胞与淋巴细胞的比值（NLR）预测微小病变型肾病（MCD）患者发生激素性骨坏死的价值。方法　回顾性分析经皮肾穿刺活检术诊断的329例MCD患者的临床资料。根据受检者工作特征（ROC）曲线确定NLR诊断MCD发生激素性骨坏死的最佳截断值,以截断值为界将研究对象分为低NLR组（NLR≤3.321）262例和高NLR组（NLR＞3.321）67例,比较2组患者的基线临床指标、激素用量及时间、合用钙剂及活性维生素D3情况,分析NLR与MCD患者发生激素性骨坏死的相关性,以Kaplan-Meier生存曲线比较2组患者的关节生存率;以多因素Cox回归模型分析MCD患者发生激素性骨坏死的危险因素。结果　全部患者的总中位随访时间为38个月。高NLR组的年龄、白细胞计数、单核细胞计数、C反应蛋白、红细胞沉降率、纤维蛋白原、骨钙素、β胶原特殊序列、血尿素氮、血肌酐及发生激素性骨坏死的比例均较低NLR组高,估算肾小球滤过率较低NLR组降低（P＜0.05）。Kaplan-Meier生存曲线显示,低NLR组患者的关节累积生存率明显高于高NLR组（c2=10.130,P＜0.01）,高NLR组与低NLR组的1年、3年、5年生存率分别为82.9% 和93.5%、76.3%和88.9%、65.2%和85.6%。多因素Cox回归分析结果显示,高NLR水平是MCD患者发生激素性骨坏死的独立危险因素（HR=2.155,95%CI：1.136～4.089,P＜0.05）。结论　血NLR水平与MCD患者发生激素性骨坏死的风险相关,可作为评估MCD患者发生激素性骨坏死风险的有价值指标。     

小儿肾病综合征红细胞免疫功能的改变

目的　探讨红细胞免疫功能在小儿原发性肾病综合征中的作用。方法　采用郭氏法 ,用微量指血检测红细胞 C3b受体黏附率 (RC3b R)及红细胞免疫复合物黏附率 (RICR)。采用单项免疫扩散法 ,用静脉血检测补体 C3、C4,免疫球蛋白 Ig G、Ig A、Ig M。结果　肾病组 RC3b R、RICR与对照组比较 ,t RC3 b R=5 .76 ,t RICR=6 .81,P<0 .0 1,差异非常显著。肾病组 RC3b R与补体 C3、C4、Ig A、Ig G、Ig M直线相关 ,统计学处理 ,r C3 =- 0 .11,r C4=0 .43,r Ig A=0 .19,r Ig M=0 .0 9,P>0 .0 5 ,无相关性。r Ig G=0 .6 2 ,P<0 .0 5 ,呈正相关。结论　小儿原发性肾病综合征存在着红细胞免疫功能障碍 ,并且与体内多种免疫因素有关 ,是临床治疗中一项重要的观察指标。     

Corticosteroids therapy and peptic ulcer disease in nephrotic syndrome patients

AIMS

Whether corticosteroids induce peptic ulcer disease (PUD) remains uncertain. The study evaluated and compared the occurrence of PUD between nephrotic patients receiving oral prednisolone therapy and nephritic patients without steroid therapy.

METHODS

The prospective case control study compared 60 nephrotic syndrome patients who received 60 mg daily prednisolone therapy for 3 months with 30 age-and sex-matched nephritic patients without steroid therapy. Each patient underwent endoscopic examination and tissue and blood sampling before and after the study. Examined parameters included Helicobacter pylori (H. pylori) infection, and gastric and serum prostaglandin (PG) E₂ and thromboxane (TX) B₂ concentrations. The primary endpoint was the occurrence of endoscopic peptic ulcers between the two groups, while the secondary end point was the occurrence of ulcer complications.

RESULTS

The two groups were comparable in sex, age, smoking habits, alcohol drinking, past history of PUD, H. pylori infection rate and serum creatinine. There were no differences in the occurrence of endoscopic peptic ulcers (1.6% vs. 3.3%) and ulcer complications (0% vs. 0%), pre-therapy gastric PGE₂, and pre- and post-therapy gastric TXB₂, serum PGE₂ and serum TXB₂ between the two groups. However, there was significantly lower post-therapy gastric PGE₂ concentrations in the prednisolone group.

CONCLUSIONS

Three-month therapy with 60 mg daily prednisolone caused few endoscopic ulcers (1.6%) and no ulcer complications in nephrotic patients. Corticosteroids therapy did not increase PUD in nephrotic syndrome patients [odds ratio 0.492 with 95% confidence interval (CI) 0.03, 8.142, P= 0.620]. Further larger studies are needed to clarify the role of corticosteroids in PUD.     

肾病综合征患儿细胞免疫功能的检测及其意义

目的 探讨肾病综合征(NS)患儿细胞免疫功能的变化及其意义.方法 应用流式细胞仪检测45例NS患儿及30例健康对照组外周血T淋巴细胞亚群及自然杀伤细胞(NK)的水平.结果 NS患儿活动期CD3+、CD4+、CD4+/CD8+比值、NK[CD(16+56)]+细胞均明显低于Ns缓解期和对照组(P<0.05),缓解期CD4+细胞明显低于对照组(P<0.05).结论 NS的发病与细胞免疫功能紊乱密切相关,这为调节患儿免疫功能的相关治疗提供一定依据.     

Pharmacological treatment of nephrotic syndrome

In the "minimal change" nephrotic syndrome (MCNS), steroids induce remissions in most cases (93% in children and 81% in adults). Response occurs in an average time of 11 days in children but may take up to 16 weeks in adults. The dose of prednisone is 60 mg/m(2)/day (maximum 80 mg/day) given usually for 4 weeks and then reduced to 40 mg/m(2) on alternate days for a few weeks. The medication may be discontinued abruptly at the end of the course of treatment. Children who do not respond to prednisone should be biopsied. Those whose biopsy shows minimal changes may have a remission with more prolonged alternate day treatment, or may need cyclophosphamide or cyclosporine. Relapses of nephrotic syndrome are common and usually respond to steroids given daily until remission, then on alternate days for 4 weeks. In adults prednisone on alternate days for 1 year after the presenting attack decreases the risk of relapse. Toxicity is a problem only in steroid-dependent patients who may require other drugs. Cyclophosphamide (2-3 mg/kg/day) and chlorambucil (0.15 mg/kg/day) for 8-12 weeks induce long-term remissions in 25-70% of children and are also beneficial in adults. The effectiveness of cyclophosphamide in steroid-resistant MCNS is limited to bringing about a faster remission. In children with MCNS who are initially steroid-responsive and later become resistant, cyclophosphamide usually induces a remission and restores steroid responsiveness. The toxicity of cyclophosphamide and chlorambucil in MCNS has generally been mild and reversible. It includes bone marrow depression, hemorrhagic cystitis, some hair loss, infertility and, extremely rarely, oncogenesis. The risk of gonadal toxicity is minimized with total doses below 200 mg/kg for cyclophosphamide and 7-10 mg/kg for chlorambucil. Seizures have been reported in 8% of children treated with chlorambucil. Cyclosporine (6 mg/kg/day initially) produces complete remissions in 85% of children and 79% of adults with steroid dependence and in 67% of children and 61% of adults with steroid resistance. Levamisole may be helpful in steroid-dependent cases, but data about its efficacy are conflicting. Cyclosporine and levamisole usually do not induce permanent remissions.     

硫普罗宁致肾病综合征的报告分析

目的:探讨硫普罗宁导致肾病综合征的特点及治疗,为临床安全用药提供参考.方法:经查阅相关文献,对硫普罗宁引起肾病综合征患者的临床病理特点、治疗预后等进行总结,并对我院收治的2名因使用硫普罗宁导致肾病综合征患者的实际情况进行分析.结果:文献报道29例硫普罗宁引起的肾病综合征病例,其中,男性16倒,女性13例;年龄最小20个月,最大73岁;用药1月～2年的患者有14例;9例行肾活检,以膜性肾病为主(6例);29例患者中给予激素治疗者3例,免疫抑制剂治疗者1例,其他给予对症支持治疗者25例,所有患者均恢复正常,完全恢复时间小于5周.我科收治2例患者,男女各1名,年龄分别为76岁和62岁,院外抗结核常规给予硫普罗宁保肝治疗,分别在用药9、11周后出现大量蛋白尿、低蛋白血症,临床诊断肾病综合征;1例肾活检病理诊断肾小球微小病变,未给予激素及免疫抑制剂治疗,停用硫普罗宁后1～2个月肾病自行缓解.结论:硫普罗宁长期应用可以导致肾病综合征,病理类型表现多样,多数停药后可自行缓解.建议长期使用该药的患者应注意肾脏损害,早期发现及时停药,预后较好.     

Lithium and the nephrotic syndrome

The authors report the occurrence of the nephrotic syndrome in association with the use of lithium carbonate in a 41-year-old man, review other reports of this adverse effect, and discuss implications for the clinician.