Daily single-dose and daily reduced-dose prednisone therapy for children with the nephrotic syndrome

Most current reference sources recommend that initial therapy for minimal lesion nephrotic syndrome consist of prednisone, 60 mg/m2 per 24 hours or 2 mg/kg per 24 hours, given in divided doses, and that this regimen be repeated for each relapse. The need for divided-dose daily-administered prednisone is predicated on anecdotal observations that single-dose daily administration is not effective. Because single-dose daily-administered and reduced-dose daily-administered prednisone has been used to treat this condition for several years, experience with these regimens in nephrotic children was analyzed. Forty-one patients were studied, including 22 treated from the onset of their disease. Of these 22, 17 (77%) responded to single-dose daily-administered prednisone (2 mg/kg); after subsequent biospy, each of the nonresponders proved to have lesions other than minimal change disease. The mean response time with single-dose daily-administered prednisone (9.6 days for treatment of the initial onset of nephrotic syndrome and 11.1 days for treatment of relapses) was comparable to that previously reported with divided-dose regimens. In 14 patients with frequent relapses, a single reduced-dose daily-administered dose of prednisone (0.2 to 1.5 mg/kg/d) successfully induced remissions in 55 of 63 relapse episodes. It is concluded that a single morning dose of prednisone effectively induces remission in children with minimal lesion nephrotic syndrome. Among selected patients with frequent relapses, additional steroid sparing may be achieved by the use of this regimen with reduced doses during treatment of relapses.     

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]     

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.     

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)     

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).     

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.     

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.     

Long-term outcome of primary nephrotic syndrome.

One hundred and fourteen children with primary nephrotic syndrome were followed up prospectively for periods of between 5 and 14 years. Urine samples from 94 of them became protein-free during the initial 8-week course of prednisone, and the outcome for these children was good: 74 of them have been free of symptoms for at least 3 years, 18 have had relapses during the last 3 years, and only one child still has proteinuria. All these children have normal renal function and blood pressure. One child died accidentally. Twenty children did not respond to the initial prednisone treatment. Thirteen of them had remissions later, of whom 2 have had relapses during the last 3 years. Seven were totally resistant to prednisone 4 of whom died in renal failure, the remaining 3 have persistent proteinuria with normal levels of creatinine; one has high blood pressure too. Remission during the initial treatment indicated a good prognosis, but two-thirds of the initial non-responders also fared well.     

Varicella vaccination in children with nephrotic syndrome: a report of the Southwest Pediatric Nephrology Study Group

OBJECTIVE: To evaluate the safety and immunogenicity of varicella vaccine in children with nephrotic syndrome, including those taking low-dose, alternate-day prednisone. STUDY DESIGN: Prospective, open-label, multicenter clinical trial of varicella vaccine in a 2-dose regimen in US and Canadian children (12 months to <18 years) with nephrotic syndrome. Varicella Zoster Virus (VZV) antibody levels were measured after the first and second vaccine dose and yearly for 2 years. Patients were monitored for adverse reactions to vaccine, exposure to varicella, dermatomal zoster, and chickenpox. RESULTS: Twenty-nine children, mean age 4.9 (SD 1.9) years, 45% receiving every-other-day steroids, received 2 vaccine doses. All patients seroconverted and had VZV antibody levels considered protective against breakthrough varicella (>or=5 gpELISA units) after 2 doses. At 2-year follow-up, all patients retained detectable antibody, and 91% (21 of 23) had levels >or=5 gpELISA units. There were no adverse events associated with vaccination. CONCLUSIONS: Varicella vaccine was generally well tolerated and highly immunogenic in children with nephrotic syndrome, including those on low-dose, alternate-day prednisone.     

Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after twelve-month follow-up: results of a three-year national surveillance study

Aim: To describe the demographic, clinical features, steroid response, histopathology and complications of all children diagnosed with idiopathic nephrotic syndrome (INS) in New Zealand over a 3-year period. Methods: A questionnaire seeking relevant clinical information was sent to all paediatricians who reported a new case of nephrotic syndrome to the New Zealand Paediatric Surveillance Unit. A follow-up questionnaire was sent to reporting paediatricians after the first 12 months of follow-up. Results: The incidence was 1.9 children per 100,000 under age 15 years. There was no significant difference in INS between ethnic groups. Approximately 80.4% were steroid responsive with median time to response of 8.4 days and mean time to relapse was 15.1 +/- 12.1 weeks (10.1-19.8 95% confidence interval). Follow-up at 12 months after diagnosis showed that two-thirds were either steroid dependent or frequent relapsers. Steroid resistance patients had a more variable course with some developing chronic renal failure and other remaining persistently nephrotic. Conclusion: The incidence and outcome of children with INS are similar to overseas studies. A large variety of steroid treatment regimens were noted. Current evidenced-based guidelines to treat INS were used infrequently.     

Long-term, small dose prednisone therapy in frequently relapsing nephrotic syndrome of childhood. Effect on remission, statural growth, obesity, and infection rate

A prospective study was performed to evaluate the effect of long-term small-dose prednisone therapy in frequently relapsing nephrotic syndrome (NS); 37 patients were included, with a relapse rate 4.6/patient/year (range, 3-8) (mean age, 6.7 years; range, 2-15 years). Prednisone was started 2 mg/kg/day once remission was induced. Prednisone was progressively reduced over weeks until 10 mg/day was reached, and then the daily dose was changed to 10 mg on alternate days. On follow-up (mean, 25.4 months; range, 10-58 months), only five had subsequent relapses and their relapse rate decreased significantly to 1.2/patient/year (p less than 0.05). Forty-six episodes of infection were associated with exacerbation of NS; 41 of these excerbations remitted spontaneously without an increase in the dose of prednisone. Serial height and weight measurements revealed evidence of improved height velocity and obesity persisted in only two of 13 initially obese children.     

Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight week with 12 week course. Report of Arbeitsgemeinschaft für P?diatrische Nephrologie.

In a prospective study (Cytotoxic Drug Study II), 18 children with steroid dependent nephrotic syndrome and steroid toxicity were treated with cyclophosphamide (2 mg/kg body weight/day) for 12 weeks in combination with reducing doses of prednisone (group A). This group was compared retrospectively with 18 children with steroid dependent nephrotic syndrome, studied as part of the Cytotoxic Drug Study I, and who had received cyclophosphamide for eight weeks (group B). There were no differences between the groups in age at the onset of the nephrotic syndrome, age at entry into the study, and duration of the nephrotic syndrome before entry into the study. The number of relapses during the six months before the treatment was the same in both groups. Two years after treatment 12 of 18 children treated with cyclophosphamide for 12 weeks were still in remission. By contrast, only four of of 18 children treated with cyclophosphamide for eight weeks were still in remission. The cumulative rates of sustained remissions were significantly higher (67% and 22%, respectively) in group A. All relapses were observed within 400 days of stopping cytotoxic treatment. No severe side effects of cyclophosphamide occurred up to two years after treatment had been stopped. We conclude that for children with steroid dependent nephrotic syndrome and steroid toxicity cyclophosphamide treatment should be prolonged to 12 weeks to increase the likelihood of a prolonged remission.     

Chronic inflammatory demyelinating polyneuropathy in children: follow-up investigation and results of prednisone-azathioprine treatment

We collected 20 children with chronic dysimmune polyneuropathy (median age at onset 7.5 years) and performed a follow-up investigation after a median of 12 years. At onset all had areflexia; cerebrospinal fluid total protein was increased in 17 (85%) of 20. Nerve conduction velocity was pathological in 17 of 18 and sural nerve biopsy in nine showed evidences of de- and remyelinization in eight. An underlying subclinical hereditary polyneuropathy was indicated in one parent in 11 of 14 re-examined children. Onset was preceded by an infection or vaccination in 12 (60%) of 20. The initial impairment was often impressive and one patient was treated on a ventilator.Treatment principles included induction with prednisone 1–2 mg/kg per day for 6 weeks, tapered off during 3–4 weeks and maintenance with azathioprine 2–3 mg/kg per day for 2 years. Accordingly, 17 were given corticosteroids and 15 also azathioprine. Seven (35%) had a monophasic and 13 (65%) a relapsing-remitting course with 35 relapses (mean 1.7 per affected patient in the whole and 2.8 in the relapsing group). The relapses tended to become successively shorter and milder. The group with combined short-term corticosteroid and long-term azathioprine treatment had fewer relapses (1.6 per patient) than the group with corticosteroids and short-term azathioprine (2.3 per patient).At follow-up two of three in the non-treated group, with generally more benign courses, had no remaining handicap, three of six (50%) treated with short-term prednisone and short-term azathioprine, and eight of 11 (73%) given short-term corticosteroids and long-term azathioprine had no remaining handicap according to the WHO handicap score. Strength was most affected in hand, hip and foot muscles. Corticosteroid dependency and long-term side-effects were avoided in all. We consider the outcome encouraging.     

Efficacy of levamisole in children with frequently relapsing and steroid-dependent nephrotic syndrome

Objectives

To assess the efficacy of levamisole in frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome.

Study Design

Retrospective analysis of hospital case records.

Setting

Pediatric nephrology department of a tertiary referral pediatric hospital.

Participants

62 children with frequently relapsing nephrotic syndrome and 35 children with steroid-dependent nephrotic syndrome.

Methods

Case records of children who were diagnosed as steroid-dependant or frequently-relapsing nephrotic syndrome from June 2004 to June 2011, were reviewed. Levamisole was given daily (2 mg/kg/d) along with tapering doses of alternate day steroids after remission on daily steroids.

Results

Levamisole was effective in 77.3% children with a better (80.6%) efficacy in frequently relapsing nephrotic syndrome. A total of 34 children completed 1 year follow-up post levamisole therapy. The cumulative mean (SD) steroid dose 1-year before therapy was 4109(1154) mg/m² and 1-year post therapy was 661 (11) mg/m² (P<0.001). The relapses were also less during the period of post-levamisole therapy.

Conclusion

Levamisole is an effective alternative therapy in frequently relapsing and steroid-dependent nephrotic syndrome.     

吗替麦考酚酯治疗儿童难治性肾病综合征

目的：观察吗替麦考酚酯（MMF）分散片联合泼尼松治疗难治性肾病综合征（RNS）的疗效性及安全性。方法：采用前瞻性多中心对照方法，10个中心共142例患者入选。治疗组87例，对照组55例。治疗组以MMF分散片（每日30～40 mg/kg）联合泼尼松（每日0.5～1 mg/kg）治疗，服MMF 6个月后，如无效应者停药，有效者减量维持治疗6个月，维持剂量每日10～20 mg/kg；对照组以环磷酰胺（CTX）冲击，每2周连用2 d，每日10 mg/kg 联合泼尼松治疗，疗程3个月，随后第4，7，10个月的第1天分别给予CTX 500 mg/m2，静脉点滴1次。泼尼松服用2～3个月开始减量。定期检测尿蛋白、肝肾功能及药物副作用。观察随访期共1年。结果：MMF治疗组87例中58例获完全效应，16例部分效应，9例表现为早期效应，4例治疗失败，治疗总有效率95.4％，尿蛋白转阴67例（77％）；CTX组55例中35例获完全效应，9例部分效应，1例早期效应，10例治疗失败，治疗总有效率81.8％，尿蛋白转阴36例（65.4％）。两组尿蛋白转阴率统计学差异无显著性，有效率MMF治疗组较CTX组高，而且有统计学意义(P<0.01)。尿蛋白转阴天数、低蛋白血症恢复天数、尿量恢复时间、高脂血症、水肿消退时间等方面MMF明显优于CTX。MMF治疗组用药期间主要副作用有一过性转氨酶升高3例次、感染32例次、消化道症状11例次、月经紊乱、肌肉颤动各1例次；对照组发生转氨酶升高9例次、感染30例次、消化道症状15例次、血红蛋白降低4例次、白细胞降低2例次、脱发7例次。结论：结果表明，推荐MMF每日20～35 mg/kg联合泼尼松0.5～1 mg/kg治疗难治性肾病综合征，尿蛋白转阴率不劣于CTX，而且起效时间较CTX短，药物副作用少。     

Pulse Methylprednisolone Therapy in Severe Idiopathic Childhood Nephrotic Syndrome

ABSTRACT. The effect of methyl prednisolone therapy (PM) was studied in 18 children with severe idiopathic nephrotic syndrome (NS). Eight patients were defined as "corticosteroid-resistant" because there was no response to treatment after a minimum of 4 weeks of 2 mg/kg/day of prednisone; 10 patients had a corticosteroid-dependent NS with frequent relapses which occurred under a high threshold dose of prednisone (1 mg/kg/day). Each patient received 4–6 pulses of 1 g/1.73 m² methylprednisolone. Tolerance was generally good. PM therapy permitted a more rapid remission than oral prednisone (average 9±4 days vs. 22±9 days). Remission occurred in 5 of the 8 corticosteroid-resistant patients three of these 5 patients developed corticosteroid-dependent NS. For the children with a corticosteroid-dependent nephrotic syndrome, PM therapy did not affect the threshold dose of prednisone.     

Cyclic combination chemotherapy for acute lymphoblastic leukemia recurring after elective cessation of therapy

Cyclic combination chemotherapy was administered to 26 patients with acute lymphoblastic leukemia who had relapsed in the bone marrow greater than or equal to 6 months after elective cessation of therapy. Each patient had been in initial continuous complete remission for 36-111 months (median, 47 months). Prednisone, vincristine, and doxorubicin induced second complete remissions in all patients within 1 month. Continuation therapy consisted of alternating 6-week courses of 6-mercaptopurine/methotrexate and vincristine/cyclophosphamide with intervening reinforcement courses of prednisone/doxorubicin, for a total of 18 months. All patients received 4 weeks of late intensification therapy with the same agents used for remission reinduction. Periodic intrathecal methotrexate was given as reprophylaxis for subclinical central nervous system leukemia. The estimated rate of continuous failure-free survival at 5 years is 31% +/- 17% (2 SE). Eight patients remain free of leukemia for 42 + to 65+ months after completing therapy a second time. Adverse second events included 11 hematologic, 1 testicular, and 3 meningeal relapses. Patients who relapsed at more than 12 months after the completion of initial treatment have had significantly longer second remissions than patients whose first remissions were shorter (p = .04). None of the other six factors we analyzed showed predictive strength. These end results indicate that intensive cyclic continuation chemotherapy, as described here, will secure durable second remissions in approximately one-third of the children with late bone marrow relapses.     

儿童原发性肾病综合征频反复相关因素分析

目的 通过对原发性肾病综合征(PNS)患儿临床资料统计分析,探讨小儿PNS频反复的影响因素.方法 收集2007年1月至2010年2月于我科诊断为PNS的患儿住院及门诊随访病历,对获得的完整临床资料进行分析.结果 245例激素敏感型肾病综合征患儿中,非频反复202例(82.4%),频反复43例(17.6%).单因素分析结...     

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.     

Cyclosporin therapy in steroid-dependent nephrotic syndrome

Abstract Five children with multiple relapsing steroid-dependent nephrotic syndrome were treated with continuous cyclosporin for periods ranging from 18 to 48 months. Renal biopsy showed mild mesangial proliferation in three of the children and minimal change in two. All children previously had been treated with cyclophosphamide. Cyclosporin was started during remission at 5 mg/kg per day. If a relapse occurred the dose was increased until a trough blood level of 100–250 ng/mL (HPLC) was achieved. In the initial 12 months of treatment, the mean number of relapses decreased from 6.4±0.54(s.d.) per annum to 1.6±1.3 per annum (P<0.01). Cyclosporin was effective in maintaining long-term remission in four of the five patients. Side effects included hypertrichosis (5) and gum hyperplasia (1). The mean creatinine clearance decreased from 126±16 to 97=22 mL/min per 1.73 m² (P = NS). A renal biopsy in all five patients after 12 months therapy showed no nephrotoxicity. A further biopsy in one patient after 4 years therapy showed interstitial fibrosis. Cyclosporin should be considered in children with steroid-dependent nephrotic syndrome who show signs of steroid toxicity and have only a short remission period after cyclophosphamide. Serial renal biopsies are recommended if prolonged therapy is used.