儿童激素耐药型肾病综合征治疗进展

原发性肾病综合征(PNS)是儿童最常见的肾小球疾病之一,足量泼尼松口服4周后如仍未缓解则为激素耐药型肾病综合征(SRNS)。根据是否存在单基因致病,分为特发性SRNS及遗传性SRNS。目前激素联合钙调神经磷酸酶抑制剂(CNI)是治疗特发性SRNS首选推荐治疗方案,50%~70%的患儿可达完全或部分缓解;少部分特发性SR...     

TRPC6基因变异致儿童激素耐药型肾病综合征四例并文献复习

目的:探讨TRPC6基因变异致儿童激素耐药型肾病综合征(SRNS)的特征、治疗及预后。方法:回顾性分析2017年1月至2019年12月在上海市儿童医院肾脏风湿科住院的4例(SRNS)且经基因检测为TRPC6变异患儿的临床资料。以“肾病综合征”“TRPC6”“儿童”“nephrotic syndrome”“TRPC6 variation”“child”为检索词,检索建库至2020年8月中国知网数据库、万方数据库、维普数据库及PubMed数据库并进行文献复习。结果:4例SRNS患儿中,男1例、女3例,起病年龄4岁1月龄至12岁2月龄。临床均以浮肿、大量蛋白尿、低蛋白血症起病,4例出现贫血,2例出现继发性甲状旁腺功能亢进,1例肾萎缩。肾脏病理结果示1例为免疫复合物相关性肾炎,3例为局灶节段肾小球硬化。4例患儿病初予足量糖皮质激素治疗4周以上,均为激素耐药,后予糖皮质激素联合免疫抑制剂(如环磷酰胺、钙调神经磷酸酶抑制剂、霉酚酸酯)治疗,症状没有改善。4例患儿2~6个月进展为终末期肾病。全外显子测序显示4例患儿TRPC6基因变异类型分别为c.2684G>T、c.523C>T、c.2678G>A、c.2683C>T,均为新发变异。文献检索纳入中文文献1篇,外文文献9篇,共27例。汇总分析31例(包括本组)病例资料,其中18例错义变异,移码变异、同义变异、剪切变异各1例。起病年龄4月龄至14岁,18例患儿临床表现为大量蛋白尿、低蛋白血症,6例仅表现为蛋白尿,19例患儿病理类型为局灶节段肾小球硬化,IgA肾病、微小病变各2例,塌陷性肾小球病、C1q肾病、免疫复合物相关性肾小球肾炎各1例。18例患儿激素治疗无效,11例钙调神经磷酸酶抑制剂类药物无效。该疾病预后不佳,12例患儿出现肾衰竭,进展至终末期肾病时间为4个月至13.8年。结论:TRPC6基因变异致SRNS的患儿起病年龄较小,病理特征多为局灶节段肾小球硬化,激素及免疫抑制剂治疗多无效,进展迅速预后差。     

儿童激素耐药型肾病综合征的诊疗现状

儿童激素耐药型肾病综合征(SRNS)是指以泼尼松足量治疗＞4周尿蛋白仍为阳性者.SRNS诊断包括临床诊断、病理诊断和病因诊断.SRNS病因分为T淋巴细胞功能紊乱和肾小球滤过屏障的原发性缺陷2类.因T淋巴细胞功能紊乱所致的儿童SRNS推荐钙调蛋白磷酸酶抑制剂作为初始治疗方案.因肾小球滤过屏障的原发性缺陷所致儿童SRNS绝大多数对激素和免疫抑制剂耐药,治疗该类SRNS的新药急待研发.     

儿童肾病综合征激素耐药机制研究进展

激素耐药是儿童原发性肾病综合征治疗的难点,其产生机制较复杂。近来研究发现,多药耐药基因1(multidrug resistance gene l,MDR1)及其产物P-糖蛋白170(P-glycoprotein170)、糖皮质激素受体( glucocorticoid receptor,GR)、肾脏病理、基因突变、并发症等均与激素耐药密切相关。该文就儿童原发性肾病综合征的激素耐药机制进行综述,以指导临床治疗。     

糖皮质激素受体与儿童激素耐药型肾病综合征研究进展

原发性肾病综合征是儿科常见的泌尿系统疾病,糖皮质激素是其首选和基础用药,然而临床中约有10％ ～ 20％的患者对激素耐药,耐药机制复杂.研究显示糖皮质激素受体参与了耐药的发生.本文就肾病综合征患儿糖皮质激素受体表达及其基因多态性做一综述.     

加强对儿童激素耐药型肾病综合征的临床研究

自1956年首篇报道糖皮质激素治疗原发性肾病综合征的文章发表以来，糖皮质激素在肾病综合征的应用已逾半个世纪，依然是目前肾病综合征的主要治疗药物。而困扰临床医师的激素耐药型肾病综合征(SRNS)，由于其对糖皮质激素的治疗缺乏反应，一方面增加了后续治疗的难度；同时由于病情得不到及时和有效的控制，预后也不乐观。     

激素耐药型与激素敏感型肾病综合征儿童尿液双向电泳图谱分析

目的建立激素耐药型原发性肾病综合征(SRNS)儿童与激素敏感型原发性肾病综合征(SSNS)儿童尿液全蛋白双向凝胶电泳(2-DE)图谱,分析差异的蛋白质位点,为研究原发性肾病综合征(INS)糖皮质激素耐药的机制提供依据。方法病例来源于湘雅二医院儿科住院部,收集时间为2005-01-2005-10,入选的INS患儿依据中华医学会儿科学分会肾脏病学组制定的诊断标准,分为3组,每组5例。利用2-DE技术分离SRNS与SSNS(治疗前、后)儿童尿液总蛋白质,Image Master 2D V3.01分析软件进行凝胶图像分析。结果获得了图像清晰、分辨率高的SRNS组、SSNS(治疗前)与SSNS(治疗后)组儿童尿液2-DE图谱,3组点数分别为(206±8)个、(204±5)个、(55±5)个;SRNS组与SSNS组(治疗前)尿液2-DE凝胶共筛选出差异蛋白质点66个;SRNS组与SSNS组(治疗后)尿液2-DE凝胶共筛选出差异蛋白质点33个。结论该研究成功建立了分辨率高且重复性较好的SRNS与SSNS儿童尿液全蛋白的2-DE图谱;通过组间尿液2-DE图谱分析,发现了一些可能与INS激素耐药或敏感有关的蛋白质位点,为进一步运用蛋白质组学技术寻找与INS激素耐药抑或激素敏感相关的蛋白质打下了基础。     

儿童激素耐药型肾病诊疗新进展

激素耐药型肾病(SRNS)在临床上易反复及迁延不愈,甚至发展为终末期肾病,一直是儿童肾病综合征治疗的难点。近年来国内外对儿童SRNS的诊断标准、病理类型、治疗方法进行了积极的探讨研究。该文对儿童SRNS诊断和治疗的最新进展进行综述。     

肾病综合征激素耐药型的诊治

肾病综合征激素耐药型的诊治杨霁云肾上腺皮质激素（简称激素）用于治疗小儿肾病综合征（简称肾病）逾４０年，已作为该征之首选药用于临床。虽多数患儿可由之诱导缓解，但勤复发、激素依赖及激素耐药仍为治疗棘手的问题，而常称之“难治性肾病”。一、概述根据我国儿科肾...     

儿童激素耐药型与激素敏感型肾病综合征尿蛋白组学的初步研究

目的：筛选和鉴定激素耐药型（SRNS）与激素敏感型原发性肾病综合征（SSNS）尿液中差异表达的蛋白质,寻找可能与肾病综合征激素耐药和激素敏感相关的蛋白质。方法：SSNS治疗前后病例、SRNS、正常对照各5例,提取尿液全蛋白,采用双向凝胶电泳建立全蛋白凝胶图谱;银染后用Image Master 2D V3.01软件分析差异表达蛋白质点,利用MALDI-TOF-MS分析获得肽质量指纹图谱,通过Mascot软件进入NCBI数据库,鉴定出差异表达蛋白质。结果：SRNS组与SSNS治疗前组尿液2-DE凝胶比较有差异蛋白质点66个,其中仅出现于SRNS组24个、SSNS治疗前组27个;SSNS治疗后组与正常对照组尿液2-DE凝胶比较有差异蛋白质点75个,其中仅出现于SSNS治疗后组11个。对18个差异蛋白质点进行分析,鉴定出α1-抗胰蛋白酶、转铁蛋白、带异类电荷糖蛋白复合体等9类差异表达的蛋白质。结论：成功鉴定了SRNS和SSNS的尿液中存在9类差异表达的蛋白质,部分蛋白可能是SRNS或SSNS的标志物。［中国当代儿科杂志,2009,11（5）：341-345］     

Cyclosporine in steroid dependent and resistant childhood nephrotic syndrome

OBJECTIVE: To evaluate the efficacy of cyclosporine (CyA) monotherapy in steroid resistant (SRNS) and steroid dependent (SDNS) nephrotic syndrome in children. DESIGN: A retrospective study. SETTING: Tertiary kidney care center for children at Bangalore. METHODS: Forty-one children with SDNS and SRNS with normal renal functions were treated with CyA at a dose of 6 mg/kg/day initially and maintained at 3 to 4 mg/kg/day if remission was sustained. The dosage was adjusted according to the CyA blood levels in non-responders. RESULTS: The median age of patients was 93 months (range 48-936) months. Thirteen children had minimal change disease (MCNS), 10 had mesangial proliferative glomerulonephritis (GN). Ten had membrano-proliferative (GN) (MPGN) and 8 had focal segmental glomerulosclerosis (FSGS). Median age at onset of disease and median time for CyA usage from disease onset was 22 months and 16 months respectively. Median duration of CyA therapy was 24 months (range 6-72) months. The data was analyzed to determine significance of variables on the outcome. Median follow up was 71 months (range 20-205) months. Eleven children were CyA resistant. Of the remaining 30 who were CyA responders, 22 (73.33%) were CyA dependent. Seven children developed chronic renal failure (CRF). CONCLUSIONS: The predictors for CyA non-responsiveness were steroid resistance, non MCNS on biopsy and longer duration between onset of nephrotic syndrome and CyA usage, irrespective of the age of onset of the disease. There was a higher incidence of CyA dependence among young responders. Patients with CyA resistance are at high risk for significant infections and CRF.     

小儿激素敏感型肾病综合征中IL-18水平变化及意义

目的 探讨IL-18水平与小儿激素敏感型肾病综合征(SSNS)蛋白尿发生的相关性。方法 观察29例SSNS患儿在活动期和缓解期血、尿IL-18、TNF-α、IL-10的水平变化及与各临床指标的相关性。结果 SSNS患儿活动期血、尿IL-18、TNE-α水平显著高于缓解期及正常儿童;活动期血、尿IL-10水平与缓解期差异无显著性;SSNS患儿血清IL-18水平与TNF-α水平、24h尿蛋白定量呈明显正相关,尿IL-18水平与血浆白蛋白水平呈明显负相关,血清、尿IL-18水平与血清IL-10水平无明显相关性。结论 IL-18促进了Th1免疫应答,是SSNS产生蛋白尿的重要介导因子。     

Anti-oxidant vitamins and steroid responsive nephrotic syndrome in Indian children

OBJECTIVE: In recent years, it has been proposed that nephrotic syndrome is a consequence of an imbalance between oxidant and anti-oxidant activity. In the present study, the levels of micronutrient anti-oxidant vitamins (vitamin E, vitamin C, carotene and riboflavin) in Indian children with steroid responsive nephrotic syndrome were investigated. Their levels were measured during the acute proteinuric phase of the disease, as well as during clinical recovery (remission), in order to understand the possible role of nutritionally modifiable anti-oxidants in the aetiopathogenesis of the disease. METHODS: The study was a hospital based, prospective cohort study. Serum and erythrocyte vitamin E, leucocyte vitamin C, serum carotene, erythrocyte riboflavin activity and serum malonyldialdehyde (MDA) levels were measured in 30 consecutive cases of children with nephrotic syndrome (International Study of Kidney Diseases in Children (ISKDC) criteria) during the proteinuric phase of the disease and at 4 weeks after remission was induced by steroid therapy. The same biochemical parameters were measured in healthy siblings (controls) of the 30 patients. RESULTS: Mean vitamin E (serum and erythrocyte), vitamin C and carotene were significantly lower during the proteinuric phase of the disease, and there was decreased erythrocyte riboflavin activity. There was significant elevation in the serum level of MDA during this phase. In addition, all these parameters tended to improve during remission, although complete normalization did not occur. CONCLUSION: These vitamins were active in performing their anti-oxidant function, as indicated by significant depression in their levels during the acute (proteinuric) phase, followed by partial recovery during remission. It may be concluded that steroid responsive nephrotic syndrome in children is associated with oxidative stress.     

Increased frequency of steroid non-responsive nephrotic syndrome in Iranian children

During an eight year period, 66 Iranian children with nephrotic syndrome without renal failure were studied for their response to prednisone therapy. Twentysix (39·3%) of these were early steroid non-responsive. Of 40 responders, 70 per cent responded within the first 2 wk, 22·5 per cent within the second 2 wk, and 3 children during the next 4 wk of therapy. Two patients (3·03%) were steroid late non-responders.     

肾病综合征患儿肾组织原位血管紧张素转换酶mRNA表达与激素疗效关系的研究

目的　探讨肾病综合征 (NS)患儿肾脏局部肾素 血管紧张素系统 (RAS)、激素耐药、肾脏病理损害程度之间的关系 ,阐述激素耐药的部分机制。方法　 85例原发性NS患儿按激素敏感型NS(SSNS)、激素依赖型NS(SDNS)、激素耐药型NS(SRNS)分成 3组 ,选 6例行肾切除的肾肿瘤患儿的正常肾组织作为对照组。采用原位杂交的方法检测 4组患儿肾脏原位血管紧张素转换酶 (ACE)mRNA的表达水平 ;评分法半定量评估肾脏的病理损害程度。分析NS患儿肾组织ACEmRNA表达水平、激素反应性、肾脏的病理损害程度间的关系。结果　①在肾小球和小管间质区域的ACEmRNA表达水平均为SRNS组 >SSNS组 >对照组 (P <0 0 1)。②SRNS、SDNS、SSNS肾小球病理损害的评分分别为 :6 6 7± 2 4 3,4 6 8± 2 30 ,4 4 2± 2 87(P <0 0 1) ;小管间质病理损害评分分别为 :10 4 8± 3 77,7 2 0± 2 79,4 2 5± 1 4 8(P <0 0 1)。③肾组织ACEmRNA的表达与肾小球和小管间质病理损害程度呈正相关 ,相关系数分别为 0 4 82 ,0 85。结论　SRNS型NS患儿肾组织ACEmRNA表达增强 ,并且与肾脏的病理损害程度密切相关     

Adrenal responsiveness in children with steroid responsive idiopathic nephrotic syndrome

Impaired adrenal cortical responsiveness to ACTH has been reported in children with steroid responsive nephrotic syndrome. Plasma cortisol levels at 8 AM and 2 hours post ACTH stimulation were measured on 42 occasions in 33 children with steroid-responsive nephrotic syndrome. Twenty-two of 42 fasting 8 AM plasma cortisol and 39 of 42 post-ACTH plasma cortisol values were subnormal. Plasma cortisol values were similar in children evaluated prior to, immediately following or 2-24 moths after prednisone therapy. No relationship was observed between 8 AM or post-ACTH plasma cortisol values and serum albumin concentration or the presence of edema. Impaired adrenal responsiveness to ACTH was not helpful in predicting the length of clinical remission. Hydrocortisone replacement therapy given to five children with impaired ACTH-responsiveness did not alter the rate of relapses observed prior to this treatment.