Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children

Two regimens of steroid treatment for the initial attack of idiopathic nephrotic syndrome (NS) in children were compared in a controlled prospective multicentre study. Long prednisone therapy consisted of 60 mg/m² per 24 h for 6 weeks, followed by alternate day 40 mg/m² per 48 h for 6 weeks. The standard prednisone therapy was 60 mg/m² per 24 h for 4 weeks, followed by 40 mg/m² per 48 h for 4 weeks. A total of 71 children with an initial attack of idiopathic NS were allocated at random to the two groups. The cumulative rate of patients with sustained remissions after 2 years was significantly higher after the long course than after the standard treatment (49% vs 19%,P=0.0079). The mean relapse rate per patient at intervals of 3, 6 and 12 months was lower in the long-course prednisone group than in the standard prednisone group, and the proportion of children with frequent relapses during any subsequent 6 months period was lower in the long-course group than in the standard group (29% vs 57%,P=0.03). Mild side-effects of corticosteroid therapy were observed more frequently after long-course prednisone treatment. It is concluded that long-course prednisone therapy of the initial attack of steroid responsive NS is preferable to the standard regimen because it reduces the rate of subsequent relapses without increasing the risk for severe steroidal side-effects. Contributing investigators and centres were: Prof. F. R. Egli (Basel, Switzerland); Prof. G. Mau, Dr. J. Zimmermann (Braunschweig, Germany); Dr. W. Marg (Bremen, Germany); Dr. R. Mallmann (Bonn, Germany); Dr. K. Witzel (Düsseldorf, Germany); Prof. D. Michalk (Erlangen, Germany); Prof. H. Olbing (Essen, Germany); Dr. E. Bopp (Flensburg, Germany); Prof. J. Dippel (Frankfurt, Germany); Dr. H. Zappel (Göttingen, Germany); Dr. D. Schwarke (Hamburg, Germany) Prof. J. Brodehl (Hannover, Germany); Prof. K. Schärer (Heidelberg, Germany); Prof. F. Schindera (Karlsruhe, Germany); Dr. M. Kirschstein (Lübeck, Germany); Prof. H. P. Weber (Lüdenscheid, Germany); Prof. M. Brandis (Marburg, Germany); Prof. R. Eife (München, Germany); Dr. F. K. Hübner (München, Germany); Dr. K. Gellissen (Neuwied, Germany); Prof. W. Rauh (Trier, Germany).     

Mycophenolate mofetil therapy for children with intractable nephrotic syndrome

BACKGROUND: Cyclosporin A (CyA) can suppress relapses and reduce proteinuria in frequent-relapse nephrotic syndrome (FRNS) and steroid-resistant nephrotic syndrome (SRNS). However, some patients remain resistant to CyA therapy. The purpose of the present paper was to evaluate mycophenolate mofetil (MMF) treatment in pediatric patients with CyA-resistant intractable nephrotic syndrome. METHODS: MMF therapy was given to 11 patients with FRNS who had relapse despite CyA therapy, and one patient with SRNS who had been receiving combined therapy using steroid and CyA until immediately before the start of MMF. MMF was administered at a daily dose of 750-1000 mg/m(2) in two divided doses. RESULTS: Ten of the 11 patients with FRNS were able to maintain remission. Among them, seven patients remained relapse free for 1 year, and two patients had a decrease in the frequency of relapse after initiation of MMF therapy. One patient, however, had repeated cycles of remission and relapse, and was considered resistant to MMF therapy. The total prednisolone dose during the period from month 6 to month 12 after the start of MMF therapy was significantly lower than that during the 6 month period before the start of MMF therapy. The patient with SRNS, who had not achieved remission despite CyA administration, had complete remission on MMF. No serious adverse effects were seen in any of the present patients. CONCLUSION: MMF could be useful in CyA-treatment-refractory FRNS and CyA-resistant SRNS.     

Normal growth of nephrotic children during long-term alternate-day prednisone therapy

Statural growth has been evaluated in 20 prepubertal nephrotic children who received alternate-day prednisone therapy for a year at least. Bone age was assessed in 16 of these children after 1-4 years of therapy. During the follow-up 12 children showed variations in height standard deviation score (SDs) below 0.5, 7 gained more than 0.5 SDs and 1 lost 0.5 SDs. Bone age fell within the normal range for chronological age in all the children studied. On the while alternate-day prednisone therapy does not affect statural growth and bone maturation of children with lipoid nephrosis.     

他克莫司联合小剂量激素治疗儿童激素抵抗型肾病综合征21例临床分析

目的 分析评估他克莫司对治疗儿童激素抵抗型肾病综合征的疗效及其安全性.方法 采用回顾性纵向研究分析21例激素抵抗型肾病综合征患儿,他克莫司初始剂量0.10 ～0.15 mg/(kg·d),每12小时1次,定期监测血药浓度、尿常规、血常规及肝肾功能等指标.同时口服小剂量泼尼松0.20 ～0.75 rmg/( kg·d).结果 1～3个月后观察近期疗效,完全缓解者14例,部分缓解者7例,完全缓解率66.7％.16例患儿接受了肾活检,其中6例微小病变型肾病患儿中3例完全缓解,3例部分缓解;4例局灶节段性肾小球硬化患儿中2例完全缓解,2例部分缓解;5例lgM肾病及1例系膜增生性肾小球肾炎患儿均完全缓解.服药期间6例患儿出现一过性不良反应,经对症处理后均缓解.20例患儿获随访,1年内共4例复发,第2年共4例6次出现复发.结论 他克莫司对儿童激素抵抗型肾病综合征有较好的疗效,不良反应较少,大多可耐受,但服药1～2年内复发率较高,因此其长期疗效仍有待于进一步随访观察.     

Short versus long initial prednisone treatment in steroid-sensitive nephrotic syndrome in children

A total of 184 children aged, 13 months to 11 years, suffering from their first attack of steroid-responsive nephrotic syndrome were included in a randomized study. They were treated according to three treatment protocols. All children received l-2mg of prednisone/kg body weight/day (up to 80 mg daily) for 4 weeks, and thereafter 1 mg/kg body weight/48 h for the next 4 weeks. Treatment was discontinued at this point in 44 children (protocol A); in 68 (protocol B) the dose was reduced by 25% each week, tapering off to 0 at the end of the third month, while in 72 children (protocol C), after the first 2 months of initial treatment the dose was reduced by 25% each month and tapered off to 0 by the end of the sixth month. All patients completed a 2-year follow-up period after withdrawal of prednisone. Treatment results were expressed as: percentage of children relapse-free within the first 6 months and 2 years after withdrawal of treatment, and average number of relapses per patient per year. The best results were obtained in children who had been treated for 6 months: 65.3% of them remained relapse-free within the first 6 months and 50% over the entire 2-year follow-up period; the number of relapses per patient per year in this group was 0.49. The respective values for children treated 2 and 3 months were: 36.4% and 32.4% for the 6-month period; 27.3% and 20.6% for the 2-year period; the numbers of relapses per patient per year were 0.79 and 0.77, respectively. The frequency of corticosteroid side effects such as transient hypertension and cushingoid obesity during the initial treatment, and growth retardation or recurrent "respiratory tract" infections observed during the following 2-year follow-up period, did not increase after prolongation of the initial treatment. Initial treatment period, steroid-sensitive nephrotic syndrome
J Ksiek, Department of Nephrology, Child Health Centre, 04-736 Warsaw, Poland     

Comparison of different regimens of prednisone therapy in frequently relapsing nephrotic syndrome

The long-term results of four different regimens of prednisone therapy were compared in 32 children with steroid sensitive, frequently relapsing idiopathic nephrotic syndrome with minimal glomerular lesions on renal biopsy. Prednisone was administered according to the following dosage schedules: 1) long-term daily, 2) standard intermittent, 3) standard alternate-day, and 4) short-term daily. Over a mean observation period of 7 years patients without steroid dependency received 19 mg/m2/day. Relapse free intervals were the longest with long-term daily prednisone therapy compared to the other three regimens. In frequently relapsing patients without steroid dependency the relapse free intervals were similar with either intermittent or alternate-day prednisone therapy (median 75d); however, they were significantly shorter with short-term prednisone therapy (median 33d). In frequently relapsing patients with steroid dependency the time of remission was generally shorter than in patients without steroid dependency (median 25d vs. 69d) with no benefit of any of the different forms of short-term treatment.     

利妥昔单抗对儿童难治性肾病综合征的治疗进展

难治性肾病综合征是导致儿童终末期肾脏病的主要原因之一,也是临床治疗的棘手问题.虽然包括免疫抑制剂在内的多种治疗方法已经对儿童难治性肾病综合征表现出了良好的治疗效果以及安全性,但是仍有很多患儿不能获得缓解.近年来,新型免疫抑制剂利妥昔单抗用于治疗难治性肾病综合征取得了较好效果,很多病例分析以及临床试验对利妥昔单抗治疗儿童难治性肾病综合征的有效性进行了报道.该文就该药治疗儿童难治性肾病的疗效和安全性等作一综述.     

Long-term prognosis for children with nephrotic syndrome

Follow-up survival and health information were obtained, after a median of 27.5 years, from 132 patients who had been seen originally as children with nephrotic syndrome between 1951 and 1967. Ninety seven patients were alive. Recurring edema or proteinuria, or both, persisted in 15 percent of those still alive. Eight of 11 parous women reported relapses during pregnancy. There was no apparent increase in malignancies, atopic diseases, clinical defects in cell-mediated immunity, or cardiovascular diseases. Twenty two patients (17%) died of renal causes between 3 months and 8 years after the onset of nephrotic syndrome. Steroid resistance was the presenting feature universally predictive of a poor outcome; nine of the 11 such patients died and the other two are now receiving hemodialysis. Hematuria was present initially in 41 percent of the patients who died of renal causes, compared with 14 percent of those still alive. Hypertension was noted on the first examination in 22 percent of those who died of renal causes, compared with 10 percent of those alive.     

不同方案泼尼松治疗儿童原发性肾病综合征的疗效及复发危险因素分析北大核心CSCD

目的探讨足量泼尼松应用4周与6周方案治疗初发原发性肾病综合征患儿的疗效及对缓解后复发的影响。方法采用非随机对照临床研究法,前瞻性纳入2017年12月至2019年5月住院并诊断为初发原发性肾病综合征的89例患儿为研究对象,分别予泼尼松2 mg/(kg·d)(最多60 mg)应用4周(4周组)或6周(6周组)治疗。之后均改为2 mg/kg(最多60 mg)隔日应用4周,之后逐渐减停。定期随访1年。比较两组维持缓解时间、复发率等指标,并采用Cox回归分析复发的危险因素。结果泼尼松治疗后3个月内4周组复发率高于6周组(P<0.05);随访1年时,两组复发率、维持缓解时间及复发频率的比较差异无统计学意义(P>0.05)。起病年龄≥6岁及24 h尿蛋白定量升高是复发的危险因素(P<0.05)。结论足量泼尼松治疗初发原发性肾病综合征的方案由4周延至6周可减少患儿前3个月内的复发。临床上应高度关注起病年龄≥6岁和高水平尿蛋白量患儿,建议给予足量泼尼松治疗6周以降低复发风险。[中国当代儿科杂志,2022,24(8):853-857]     

Cyclosporin A plus prednisone treatment of steroid-sensitive frequently relapsing nephrotic syndrome in children

Recently, there have been numerous reports on the use of cyclosporin A (CyA) in children with nephrotic syndrome (NS). In this prospective study, we wanted to evaluate the efficacy of CyA together with prednisone therapy in children with steroid-sensitive frequently relapsing NS. A total of 11 children (7 boys, 4 girls) with steroid-sensitive NS were included in this study. The patients ranged in age from 3.5 to 15 years (average 8.45 +/- 4.26 years). Renal biopsy showed minimal change disease in five, mesangial proliferation in four, focal glomerulosclerosis in one and membranous glomerulonephritis in one. The NS had lasted from 13 to 113 months (average 50.27 +/- 38.60 months). The number of relapses varied from three to 10 episodes with an average of 5.9 +/- 3.3 episodes. Patients received 5 mg/kg CyA daily in two divided doses for five months and prednisone for a total of eight weeks (30 mg/m2 daily for 4 weeks followed by 30 mg/m2 on alternate days for 4 weeks). After the completion of the treatment protocol, no therapy was given unless a relapse was observed. Mean follow-up period was 14.9 +/- 5.99 months with a range from six to 26 months. Before this combined treatment, there was a mean relapse rate of 0.144 +/- 0.05 relapses month with a range from 0.088 to 0.238. After discontinuation of therapy, the relapse rate dropped to a mean of 0.0179 +/- 0.031 with a range of 0 to 0.083. In conclusion, it would appear that a combination of CyA and prednisone is effective, sustaining the remission in steroid-sensitive NS. Corticosteroids in combination with CyA may be a better approach than conventional steroid treatment in such patients.     

Intermittent versus long-term tapering prednisolone for initial therapy in children with idiopathic nephrotic syndrome

Forty-six children with steroid-responsive nephrotic syndrome were randomly allocated to receive two different prednisolone regimens for initial therapy. Twenty-nine children (group 1) received an intermittent regimen (60 mg/m2/day for 4 weeks, followed by 40/mg/m2/day on 3 days a week for 4 weeks); 17 children (group 2) had a long-term regimen (60 mg/m2/day for 4 weeks, followed by the same dose on alternate days for 4 weeks and the doses tapered by 10 mg/m2, given on alternate days every 4 weeks for 5 months). There was no difference between the two groups in the regimen used to treat relapses, steroid responsiveness, number of patients with relapses, and frequency of toxic reactions to steroids. However, the number of patients with a relapse within 6 months after initial therapy and the number of those with frequent relapses or steroid dependence were significantly higher in group 1 than in group 2 (P less than 0.05 for both). The data indicate that the long-term tapering regimen appears to be both safe and preferable to the intermittent regimen for initial therapy in children with idiopathic nephrotic syndrome.     

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.     

Alternate-day prednisone is more effective than intermittent prednisone in frequently relapsing nephrotic syndrome

In a multicenter cooperative study the effectiveness and side-effects of two most widely used regimens for prolonged interrupted prednisone treatment were compared in children with frequently relapsing nephrotic syndrome: i.e., alternate-day prednisone vs. intermittent prednisone. Sixty-four children were admitted to the study, 30 of whom were allocated to an alternate-day, 34 to an intermittent group. Sixteen patients did not complete the full trial, which left 48 children for final evaluation (23 alternate-day, 25 intermittent). The protocol consisted of two 6-month periods. During the first 6 months patients received maintenance prednisone (alternate-day = 35 mg/m²/48 h, intermittent = 40 mg/m² on 3 out of 7 days). During the second 6-month pericd no maintenance prednisone was administered unless a relapse occurred and was treated with a short course of prednisone. The alternate-day prednisone reduced the number of relapsers and the rate of relapses significantly as compared with the control period of the second 6 months. The intermittent prednisone, however, did not significantly lower the number of relapsers, but only the rate of relapses. In the alternate-day group the number of relapsers and the rate of relapses were significantly lower than in the intermittent group. Observation for toxic side-effects did not reveal any difference. It is concluded that an alternate-day regimen is preferable to the intermittent regimen, which should be abandoned in the treatment of children with the nephrotic syndrome.Supported by grants of VW FoundationParticipating centers: Basle, Switzerland: Kinderspital (F. Egli) Berlin-West: Universitaets-Kinderklinik Gesamthochschule (H. Olbing, H. J. Bachmann) Frankfurt a. M.: Universitaets-Kinderklinik (J. Dippell) Freiburg i. Br.: Universitaets-Kinderklinik (F. Schidera) Hamburg: Universitaets_Kinderklinik (F. Bläker, H. Altrogge) Hannover: Kinderklinik der Medizinischen Hochschule (J. Brodehl, H.-P. Krohn) und Kinderhielanstalt (J. Natzschka) Heidelberg: Universitaets-Kinderklinik (K. Schärer, D. Müller-Wiefel) Homburg: Universitaets-Kinderklinik (D. Krämer) Munich: Universitaets-Kinderklinik (R. Joppich) Münster: Universitaets-Kinderklinik (L. Diekmann) Stuttgart: Olgaspital (W. Hagge) Pathologist: W. Thoenes (Mainz) Statistician: B. Schneider (Hannover) Central office: Hannover, Kinderklinik der Medizinischen Hochschule (J.B)     

环磷酰胺静脉冲击治疗儿童激素依赖性肾病综合征32例疗效分析

目的　了解大剂量环磷酰胺静脉冲击疗法 (CTX PT)治疗儿童激素依赖性肾病的近期疗效以及影响疗效的相关因素。方法　总结 1991年 9月至 2 0 0 0年 6月接受CTX PT治疗的激素依赖性肾病 3 2例 ,并就其疾病类型、临床观察指标等与疗效的关系进行了分析。结果　①用CTX PT治疗 2 3例有效 (有效率 71 9% )。②影响疗效的因素主要有疾病的临床、病理类型以及血清肌酐 (SCr)水平。单纯性肾病疗效明显好于肾炎性肾病(有效率分别为 85 0 %和 5 0 0 % ,P<0 0 5 ) ;病理表现为微小病变 (MCNS)者明显好于非MCNS ;SCr水平在治疗前较高者提示可能疗效也差。CTX PT疗效与性别、发病年龄、血清白蛋白、球蛋白、血胆固醇、免疫球蛋白、2 4h尿蛋白排泄量等无关 (P >0 0 5 )。③毒副作用 :11例 (3 4 4% )未见明显CTX毒副作用 ;2 1例 (65 6% )出现不同程度的副作用 ,主要为急性胃肠道反应占 40 6% (3d内缓解 ) ,其它副作用少见 ,而且这些毒副作用均为一过性并很快恢复正常。结论　CTX PT治疗儿童激素依赖性肾病有效率为 71 9% ,影响疗效的因素主要有疾病的临床、病理类型以及SCr水平等。     

泼尼松联合霉酚酸酯与环孢霉素A治疗儿童激素耐药型肾病综合征的疗效比较

目的 比较泼尼松联合霉酚酸酯(MMF)与环孢霉素A(CsA)治疗儿童激素耐药型肾病综合征(SRNS)的疗效。方法 收集2004年1月至2013年12月住院并采用泼尼松联合MMF或CsA治疗的164例SRNS患儿的临床资料,回顾性分析泼尼松联合MMF(简称MMF组;n=112)与泼尼松联合CsA(简称CsA组;n=52)治疗儿童SRNS的临床疗效。结果 CsA组治疗后1个月的缓解率为67.3%(35/52),高于MMF组(42.9%,48/112)(PPPP结论 泼尼松联合MMF或CsA治疗儿童SRNS疗效均较好且安全,治疗3个月内CsA优于MMF。     

霉酚酸酯治疗二岁以下婴幼儿激素抵抗型肾病综合征临床研究

婴幼儿肾病综合征是儿童肾病综合征的特殊类型,大部分患儿临床表现为肾炎型肾病综合征,病理表现为非微小病变型肾病,50%～80%的患儿为难治性肾病(RNS)[1-3],且近年来有增多趋势.本研究对16例2岁以下的激素抵抗型肾病综合征联合使用霉酚酸酯(mycophenolate mofetil,MMF)治疗,探讨其疗效和安全性.     

长期隔日应用泼尼松治疗难治性肾病综合征38例

难治性肾病综合征 (RNS)是原发性肾病综合征 (NS)频复发、激素依赖和耐药病例的总称。其对常规中、短程应用激素治疗反应差、易复发、常迁延不愈。我们于 1989年 10月～2 0 0 2年 10月共收治RNS 3 8例 ,采用长期隔日泼尼松治疗[1],疗效满意 ,现报道如下。资料与方法一、临床资料　 3 8例RNS患儿均符合 1981年全国小儿肾脏病学会会议标准[2 ]。其中肾炎性肾病 2 4例 ,单纯性肾病 14例 ;男 2 2例 ,女 16例 ;年龄 <6岁 6例 ,～ 14岁 3 2例 ;接受本治疗前病程 <8个月 3例 ,～ 2年 2 3例 ,>2年 12例。表现为对激素耐药 16例 ,频复发 13例 ,…     

环磷酰胺静脉冲击联合泼尼松治疗儿童激素耐药性肾病综合征疗效分析

目的 了解大剂量环磷酰胺静脉冲击疗法（CTX－PT）治疗儿童激素耐药性肾病的近期疗效以及影响疗效的相关因素。方法 总结1991年9月－2000年3月接受CTX－PT治疗的激素耐药性肾病41例,并就其疾病类型、临床观察指标等与疗效的关系进行分析。结果 （1）本组CTX－PT完全缓解11例（26％）,部分缓解13例（31％）,总有效率58％。完全缓解的患儿尿蛋白转阴发生在第3、4、5个疗程的累计百分率分别为63％、82％和100％。（2）治疗前Scr水平较低者效果较好。CTX－PT疗效与疾病的临床、病理类型以及性别、发病年龄、病程、治疗前血清白蛋白、球蛋白、胆固醇、免疫球蛋白、24h尿蛋白排泄量等无关（P＞0．05）。（3）毒副作用：本组13例（31％）未见明显CTX毒副作用,28例（68％）出现不同程度的副作用。最常见的副作用是胃肠道反应,占51％,其次为轻度脱发（9％）,7％的患儿表现为血小板下降,血白细胞减少和反复感染均各为4％,肝功能异常及出血性膀胱炎各1例（2％）。这些毒副作用均为一过性,能自行缓解或通过对症处理后很快缓解。结论 CTX－PT治疗儿童激素耐药性肾病总有效率为58％;影响疗效的因素主要为Scr水平,疾病的临床、病理类型、性别、发病年龄、24h尿蛋白排泄量等与疗效无关。