环孢素A在小儿肾病综合征中的应用

环孢素A(cyclosporine A,CsA)自1986年开始用于治疗儿童肾病综合征(NS),是目前激素依赖或耐药型NS的选择性治疗药物之一,特别是在细胞毒性药物不耐受或出现不良反应的患儿,长期应用安全性和耐受性均较好。但在应用期间必须监测CsA的血药浓度和肾功能,对接受长期持续CsA治疗的儿童每2～3年进行1次肾活检,以发现肾毒性的组织学证据。     

环孢素A治疗儿童难治性肾病综合征疗效观察

目的观察环孢素A(CsA)治疗儿童难治性肾病综合征(RNS)的临床疗效。方法回顾性分析CsA联合泼尼松治疗儿童RNS的疗效,监测CsA治疗前后相关生化指标,并观察药物不良反应。27例患儿中激素抵抗14例,激素依赖6例,频复发7例;其中25例行肾活检,微小病变型肾病15例,局灶性节段性硬化性肾小球肾炎4例,系膜增生性肾小球肾炎4例,膜增殖性肾小球肾炎2例。CsA剂量2～5mg/(kg·d),疗程6～24个月(平均11.6±6.6个月)。结果完全缓解15例,部分缓解9例,无效3例,总有效率88.9%。激素抵抗组、激素依赖组及频复发组的疗效差异无统计学意义。激素抵抗组完全缓解者起效时间较激素依赖组及频复发组长。不同病理类型的RNS患儿对CsA的治疗反应差异无统计学意义。血胆固醇≤9.0mmol/L组的完全缓解率较血胆固醇>9.0mmol/L组高。CsA的主要不良反应依次为多毛、轻度肝损、血肌酐升高等,均不影响CsA继续使用。结论CsA联合泼尼松治疗难治性肾病综合征安全有效。     

Vascular endothelial growth factor in children with nephrotic syndrome treated with cyclosporine A

AIM: To assess the effect of cyclosporine A (CyA) on the level of vascular endothelial growth factor (VEGF) in the plasma and urine of nephrotic syndrome children. METHODS: The study material consisted of 15 children (F 6, M 9; group I) who were subjected to the following examinations: A) at the time of proteinuria relapse, before treatment with CyA, B) after 3 mo, C) after 6 mo, and D) after 12 mo of CyA administration with prednisone and convertase inhibitor. The control group (II) contained 20 healthy children. The immunoenzymatic ELISA method (R&D Quantikine) was used to determine plasma and urinary VEGF levels, while the immunofluorescence method was applied to assess CyA concentration in the plasma. The statistical program Statistica 6.0 was used for statistical analysis of the results. RESULTS: In the present study, plasma VEGF level in examination A was higher than in the control group (p<0.01). After proteinuria regression (B), it did not differ from the level observed in healthy children (p>0.05). After 6 and 12 mo of CyA administration, VEGF concentration increased and was higher than in the control group (p<0.05). In all the examinations, urinary excretion of VEGF was higher than in the control group, increasing proportionally with the duration of treatment and plasma CyA level. A positive correlation was observed between plasma and urinary VEGF levels and between VEGF and CyA concentrations in the plasma. CONCLUSION: Long-term CyA treatment of nephrotic syndrome children leads to an increase in plasma and urinary VEGF.     

Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome

Background

Cyclosporine A (CsA) has been widely used in children with steroid dependent and steroid resistant nephrotic syndrome (NS) because of its efficacy in relieving these patients from systemic side effects of steroids. However, its long term use is controversial, since chronic CsA induced nephropathy (CsAN) may develop in a considerable number of patients.

Aims and Methods

In order to clarify the risk factors for the development of CsAN, the clinical characteristics of children with steroid dependent or steroid resistant NS taking CsA (target blood trough levels 50–150 ng/ml) for more than six months, managed at a single centre, were retrospectively analysed.

Results

Thirteen of 30 children (24 boys and 6 girls) taking CsA (mean duration 43 months, range 6–144) had CsAN defined as the presence of CsA associated arteriopathy with or without striped tubulointerstitial lesions. The multivariate analysis revealed that CsA treatment for more than 36 months and an age younger than 5 years at the start of CsA treatment were independent risk factors for the development of CsAN. The univariate analysis also showed that patients with CsAN had more frequent relapses during CsA treatment than those without CsAN.

Conclusion

An alternative treatment should be seriously considered after a 36 month administration of CsA in order to prevent CsAN. Data also suggest that CsA treatment in children younger than 5 years should be avoided if possible.     

Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome.

BACKGROUND: Cyclosporine A (CsA) has been widely used in children with steroid dependent and steroid resistant nephrotic syndrome (NS) because of its efficacy in relieving these patients from systemic side effects of steroids. However, its long term use is controversial, since chronic CsA induced nephropathy (CsAN) may develop in a considerable number of patients. AIMS AND METHODS: In order to clarify the risk factors for the development of CsAN, the clinical characteristics of children with steroid dependent or steroid resistant NS taking CsA (target blood trough levels 50-150 ng/ml) for more than six months, managed at a single centre, were retrospectively analysed. RESULTS: Thirteen of 30 children (24 boys and 6 girls) taking CsA (mean duration 43 months, range 6-144) had CsAN defined as the presence of CsA associated arteriopathy with or without striped tubulointerstitial lesions. The multivariate analysis revealed that CsA treatment for more than 36 months and an age younger than 5 years at the start of CsA treatment were independent risk factors for the development of CsAN. The univariate analysis also showed that patients with CsAN had more frequent relapses during CsA treatment than those without CsAN. CONCLUSION: An alternative treatment should be seriously considered after a 36 month administration of CsA in order to prevent CsAN. Data also suggest that CsA treatment in children younger than 5 years should be avoided if possible.     

儿童肾病综合征病理类型与年龄、性别的关系

目的 探讨肾病综合征患儿的肾脏病理和性别、年龄分期的关系.方法 对1 116例经肾穿刺活检明确肾脏病理的原发性肾病综合征患儿临床资料进行回顾性分析.结果 1 116例患儿中男817例,女299例,男女比例2.73:1;平均年龄(7.3 ± 3.3)岁,其中婴幼儿期90例,学龄前期294例,学龄期409例,青春期323例.肾脏病理轻微病变(MCNS)222例,占19.9%;系膜增生性肾小球肾炎(MsPGN)726例,占65.1%;膜增生性肾小球肾炎(MPGN)55例,占4.9%;膜性肾小球肾炎(MN)27例,占2.4%;局灶节段硬化性肾小球肾炎(FSGS)86例,占7.7%.肾脏病理类型在4个年龄分期的分布差异有统计学意义,MCNS患儿以学龄前期最多,MsPGN患儿以学龄期最多,MPGN和MN患儿以青春期最多,FSGS的患儿以学龄期最多.MCNS患儿的男女比例为5.3:1,MsPGN为2.4:1,MPGN为0.96:1,MN为3.5:1,FSGS为2.7:1,肾脏病理类型在性别上的分布差异有统计学意义(P ＜ 0.05).结论 对于无法开展肾活检的医院或有肾穿刺禁忌证的患儿,可根据年龄和性别结合临床检验初步推断肾脏病理变化的轻重,进一步指导治疗、判断预后.     

Peritonitis in children with nephrotic syndrome

In a retrospective review of 214 children with nephrotic syndrome seen at Children's Medical Center and Parkland Memorial Hospital in Dallas throughout the 20-year period from 1967 to 1986, 62 cases of primary peritonitis were identified in 37 patients (17.3% rate). Streptococcus pneumoniae was the major pathogen, accounting for 38% of the cases. An additional 27% of patients had negative culture results but were clinically responsive to penicillin. Gram-negative organisms were cultured from only 3% of patients; 5% were caused by alpha-streptococci and 2% each by enterococcus and anaerobes. In 23% of cases the cause was unknown. Our findings differ from the recent trend in the literature in which Gram-negative organisms associated with these infections are increasingly implicated. The incidence and bacteriology of peritonitis do not appear to have changed significantly during the 20-year period. Clinically, peritonitis was characterized by abdominal pain (98%), fever (95%), rebound tenderness (85%), and nausea and vomiting (71%). A total of 79% of patients were either in relapse or receiving steroid therapy at the time peritonitis was diagnosed; 13% had infiltrates visible on their chest radiographs. Based on our data, it seems reasonable to initiate antimicrobial therapy in nephrotic children with suspected peritonitis using a combination of penicillin plus either an aminoglycoside or a cephalosporin. This regimen should continue until culture results are available, unless Gram-positive diplococci are identified in a Gram-stained specimen of peritoneal fluid, in which case penicillin alone should suffice.     

Sodium and potassium concentrations of red blood cells and plasma in children with nephrotic syndrome, uraemia and pyelonephritis

The sodium and potassium concentrations of the red blood cells and the plasma in 38 children with pyelonephritis (19 acute, 10 chronic and 9 healed), 5 children with uraemia, and 20 children with nephrotic syndrome were compared with those of control children. The red blood cell sodium concentration was lower in patients with acute pyelonephritis, uraemia, and steroid-treated nephrotic syndrome, and higher in those with chronic pyelonephritis and nephrotic syndrome not treated with steroids. Except in uraemic cases, these alterations were not accompanied by plasma sodium and potassium changes. The results might be explained by pathological Na+ and K+ transport processes in the red cell membrane. The possible role of extracellular fluid volume changes, sodium loss and water retention are discussed.     

肾病综合征患儿的腹痛问题

腹痛是肾病综合征患儿经常主诉的症状之一,多数情况下主要是由于肾病导致迅速产生大量腹水及肠壁水肿引起,但有些患儿腹痛明显,很可能是某些严重并发症的临床表现。该文就几种引起肾病患儿严重腹痛的病因如低血容量发作、原发性腹膜炎、血栓栓塞及胃肠道并发症进行简述,以加强对肾病患儿腹痛的重视,从而达到早期诊断、早期治疗,改善预后。     

以肾病综合征为临床表现的儿童IgM肾病临床特征

目的 探讨以肾病综合征为临床表现的IgM肾病患儿的临床特征.方法 以2005年6月至2012年6月在湖南省儿童医院肾内科住院,临床诊断为肾病综合征、病理诊断为IgM肾病的36例患儿为研究对象(A组),以同期住院,病理诊断为微小病变的肾病综合征106例患儿为对照组(B组).随访1～8年,分析其临床特征.结果 (1)对照组、研究组患儿伴有血尿者分别为3.8％及30.6％(x2=20.403,P＜0.05).(2)研究组患儿肾脏病理构成:轻度系膜增生性病变26例(72.2％),中度系膜增生性病变9例(25％),1例为局灶节段性肾小球硬化.(3)将研究组按肾脏病理分成轻度病变组及中重度病变组,对照组、轻度病变组、中重度病变组患儿激素耐药率分别为12.3％、19.2％、77.8％(x2 =24.369,P＜0.05),对照组与轻度病变组之间差异无统计学意义(P＞0.05).(4)激素耐药者联用吗替麦考酚酯治疗,对照组、研究组激素耐药患儿的缓解率分别为50％及85.7％(x2=3.60,P＞0.05).结论 以肾病综合征为临床表现的IgM肾病患儿血尿的发生率较高,肾脏病理为中度病变以上者激素耐药发生率较高,需早期联合应用免疫抑制剂治疗,吗替麦考酚酯可能成为较好的免疫抑制剂选择方案.     

肾病综合征甲状腺功能的研究

目的　探讨肾病综合征 (NS)患儿发作期和缓解期的甲状腺功能改变。方法　用放免法对 1 6例原发性NS在发作期和缓解期行血、尿T3、T4 、FT3、FT4 及血TSH水平测定。结果　发作期血清T3、T4 、FT3、FT4均低于正常 ,较缓解期及对照组显著下降 (P <0 .0 0 1 ) ,尿T3、T4 、FT3、FT4 较缓解期和对照组显著增多 (P <0 .0 0 0 1 )。结论　NS患儿发作期甲状腺功能低下 ,缓解后恢复正常 ,其主要原因可能是尿中大量蛋白丢失的结果     

Vaccinations in children with idiopathic nephrotic syndrome

Idiopathic nephrotic syndrome is the most common glomerulopathy diagnosed in children. Pathogenesis of the syndrome, frequent hospitalizations and immunosuppressive treatment cause that children with this disease belong to the high risk group in relation to frequency and severity of infection. It is therefore essential to take into consideration the vaccination of these patients. The immunization of a child may be connected with several complications including the relapse or exacerbation of the basic disease. There is still too little data which vaccinations are safe, in which period of the disease the child can be vaccinated and what is the influence of the used treatment on its efficiency. The study shows the present state of knowledge concerning the usage of some obligatory and recommended vaccinations in the group of children with idiopathic nephrotic syndrome.     

Cortisone cataract in children with nephrotic syndrome

In a group of 16 children with idiopathic nephrotic syndrome treated with corticosteroids for longer than 12 months, 9 developed a posterior subcapsular cataract (PSC). No correlation between the frequency of PSC and the duration of treatment and the total dose of treatment with steroids was demonstrable. However, the patients with PSC had received considerably higher average daily doses than those without PSC. Two patients with normal ophthalmologic findings at the end of treatment showed PSC 6 and 9 months later respectively. Only one patient acquired a signficant impairement of visus.     

长疗程环孢素A治疗儿童激素耐药型肾病综合征的疗效和预后

目的 观察激素耐药的儿童肾病综合征(SRNS)应用环孢素A(CsA)长疗程治疗的疗效并分析影响疗效的相关因素.方法 回顾性分析疗程2年的CsA治疗SRNS病例20例,男:女为3:1;平均年龄5.5岁,肾病病理类型微小病变(MCNS)15例,局灶节段肾小球硬化(FSGS)4例,系膜增生性肾炎(MsPGN)1例.结果 (1)完全缓解13例(65%),部分缓解4例(20%),CsA无效3例(15%),总有效率85%.平均随访时间40.5个月,复发率45%.(2)CsA治疗微小病变肾病的有效率为93%,非微小病变为60%,但两者差异无统计学意义.(3)毒副作用:多毛、齿龈增生和高血压的发生率分别为75%、25%和10%,2例出现可逆性的肾损伤,4例出现尿NAG/Cr增高,神经系统症状2例.3例重复肾活检未发现CsA相关的肾小管间质纤维化病变.结论 对儿童激素耐药型肾病综合征CsA长疗程治疗有良好的疗效.小剂量CsA长期治疗未发现药物相关的肾小管间质纤维化和肾功能损伤.CsA长期治疗的安全性和预后有待进一步研究.     

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目的探讨选用不同中效糖皮质激素(GC)诱导缓解治疗儿童原发性肾病综合征(PNS)的疗效。方法 2008年11月至2010年2月于天津市儿童医院住院治疗的初治PNS患儿54例,随机分为泼尼松组、曲安西龙组、甲泼尼龙组,3组分别给予相应足量激素治疗。动态监测各组24h尿蛋白定量(Upro)、血浆白蛋白(Alb)、血浆胆固醇(Tcho)的变化,同时记录服用GC后尿蛋白转阴的时间。采用半定量逆转录-聚合酶链反应(RT-PCR)方法检测患儿外周血单个核细胞(PBMCs)中糖皮质激素受体(GR)GRα和GRβ的mRNA表达水平。结果甲泼尼龙对24h Upro的降低和血浆Alb的升高作用优于曲安西龙和泼尼松,尿蛋白转阴时间甲泼尼龙组及曲安西龙组较泼尼松组短,甲泼尼龙上调GRα的能力优于曲安西龙及泼尼松,而甲泼尼龙及曲安西龙抑制GRβ表达亢进的能力优于泼尼松。结论服用GC后,尿蛋白的转阴时间、Upro与血Alb的动态变化、GR的水平均可作为PNS诱导缓解期综合评价GC疗效的有价值的客观指标。初治儿童PNSGC诱导缓解的治疗阶段选用甲泼尼龙或曲安西龙的疗效优于泼尼松。