Alternate-day prednisone is more effective than intermittent prednisone in frequently relapsing nephrotic syndrome. A report of "Arbeitsgemeinschaft für Pädiatrische Nephrologie. A controlled study of deflazacort in the treatment of idiopathic nephrotic syndrome. Idiopathic nephrotic syndrome: prevention of early relapse. Prolonged versus standard prednisolone therapy for initial episode of nephrotic syndrome. Short versus long initial prednisone treatment in steroid-sensitive nephrotic syndrome in children. [Initial therapy of primary nephrotic syndrome in children: evaluation in a period of 18 months of two prednisone treatment schedules. Chilean Co-operative Group of Study of Nephrotic Syndrome in Children]. Initial treatment of idiopathic nephrotic syndrome in children: prednisone versus prednisone plus cyclosporine A: a prospective, randomized trial. Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft für Pädiatrische Nephrologie. Controlled trial of methylprednisolone pulses and low dose oral prednisone for the minimal change nephrotic syndrome. Intermittent versus long-term tapering prednisolone for initial therapy in children with idiopathic nephrotic syndrome. Single- versus divided-dose prednisolone therapy for relapses of nephrotic syndrome. Increased maintenance corticosteroids during upper respiratory infection decrease the risk of relapse in nephrotic syndrome. Nephrotic syndrome in children: a randomized trial comparing two prednisone regimens in steroid-responsive patients who relapse early. Report of the international study of kidney disease in children. Older boys benefit from higher initial prednisolone therapy for nephrotic syndrome. The West Japan Cooperative Study of Kidney Disease in Children. A randomized study of two long-course prednisolone regimens for nephrotic syndrome in children.
nan Forty patients with steroid-dependent idiopathic nephrotic syndrome (INS), a mean follow-up of 5.5 years, and a mean number of relapses of ten were blindly assigned to either deflazacort (DFZ) (n = 20) or prednisone (PDN) (n = 20) according to a ratio of equivalence of DFZ/ PDN = 0.8. This treatment was given for 1 year. The number of relapses was significantly lower in patients receiving DFZ. After 1 year, 12 remained in remission with DFZ compared with 2 with PDN. Growth velocity was not different in the two groups. Bone mineral content, assessed by quantitative computed tomography of L1 L2 vertebrae, decreased after 1 year by 6% in the DFZ group versus 12% in the PDN group (NS). The mean body weight increase of +3.9 +/- 4.1 kg in the PDN group was higher than that of the DFZ group, +1.7 +/- 2.8 kg (P = 0.06). Cushingoid symptoms tended to be less after 12 months in the DFZ group. In conclusion, this study shows that DFZ was more effective than PDN in limiting relapses in steroid-dependent INS, and that cushingoid symptoms, weight gain, and decrease in bone mineral content tended to be less marked with this drug than with PDN. nan We have examined, in a prospective randomized controlled trial, the effect of 8- and 16-week initial steroid treatment on the course of idiopathic nephrotic syndrome (INS). Patients with a first episode of INS were randomized to receive standard 8-week prednisolone (2 mg/kg daily for 4 weeks, then 1.5 mg/kg on alternate days for 4 weeks) or prolonged 16-week prednisolone treatment (2 and 1.5 mg/kg daily each for 4 weeks, then 1.5 and 1 mg/kg on alternate days each for 4 weeks). Relapses were treated with prednisolone, 2 mg/kg daily for 2 weeks, then 1.5 mg/kg on alternate days for 4 weeks. Of 45 patients, 23 received standard therapy and 22 prolonged therapy. The mean duration of follow-up was 29.2 and 27.3 months in the standard and prolonged treatment groups, respectively. The time to first relapse was longer in the prolonged treatment (mean 222.2 days, median 120.0 days) than the standard group (mean 134.3 days, median 96.5 days). The percentage of patients with no relapse at 6 and 12 months after prednisolone withdrawal was 40.9% and 27.3% in the prolonged treatment and 21.7% and 8.7% in the standard groups, respectively. The inability to show statistically significant differences between the two groups was probably related to the small number of patients studied. Prolonged therapy did not affect the subsequent relapse rates and proportion of patients with frequent relapses and steroid dependence. The mean dose of prednisolone received, for the initial episode and relapses during the next year, was higher and associated with significant steroid toxicity in the prolonged treatment group. Our findings suggest that 16-week prednisolone treatment for the initial episode of INS may delay occurrence of the first relapse, but results in significant side effects. Prolongation of initial therapy may be useful in developing countries where frequent infections often induce early relapses. 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 1-2 mg 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.(ABSTRACT TRUNCATED AT 250 WORDS) Ninety six patients aged from 6 months to 15 years and were admitted to Chilean hospitals with the diagnosis of primary nephrotic syndrome in a period of 30 months. These patients were randomly separated in two groups, group A received prednisone for 8 weeks and group B received the same drug during 12 weeks. All patients were evaluated at 6, 12 and 18 months after the end of treatment. The moment and number of relapses per patient, accumulated percentage of relapses, relapse rate per 100 patients, total number of relapses and complications were assessed. Frequent relapsers were subjected to a kidney biopsy, leaving in the protocol only those patients that had minimal changes. Patients resistant or dependent to steroid therapy were discarded. Thus we report the results of 56 treated patients followed during 18 months. No differences in analyzed parameters were observed between the two treatment groups. It is concluded that these preliminary results do not support the prolongation of prednisone treatment in children with primary nephrotic syndrome. Previous studies of the Arbeitsgemeinschaft für Pädiatrische Nephrologie in children with steroid-sensitive nephrotic syndrome have shown that the length of initial prednisone therapy has an impact on the subsequent relapse rate. The aim of this randomized, prospective, multicenter study was to reduce the number of relapses further by increasing the initial immunosuppression: Patients with an initial attack of nephrotic syndrome were randomly allocated to treatment with 6 wk of 60 mg/m(2) per d prednisone followed by 6 wk of 40 mg/m(2) per 48 h (Pred group) or to the same prednisone treatment plus 8 wk of cyclosporine (Pred+CsA group). The primary end point was first relapse; follow-up was truncated at 2 yr. In the Pred+CsA group (n = 49 patients), the first relapse occurred later compared with the Pred group (n = 55 patients) (median 22.8 versus 12.5 mo). After 6 mo, 10.4% of patients in the Pred+CsA group experienced a first relapse versus 31.5% in the Pred group (P = 0.01); after 1 yr, 36.5 versus 51% (P = 0.15); and after 2 yr, 51 versus 50%. The mean relapse rate per patient was 0.12 versus 0.57 after 6 mo (P = 0.01), 0.63 versus 1.03 after 1 yr (P = 0.02), and 1.03 versus 2.06 after 2 yr (not significant). The significant benefit for adding CsA was lost after 9 to 12 mo. GFR remained unchanged. The subsequent treatment rate with cyclophosphamide was lower in the CsA group (five versus 12 patients) after 2 yr. With the use of logistic regression statistics, children who were younger than 7 yr show a significantly better sustained remission rate with initial CsA treatment for the 2-yr observation time (P = 0.03). It remains questionable, however, whether the intensified initial treatment with CsA could be recommended generally. Two regimens of steroid treatment for the initial attack of idiopathic nephrotic syndrome (NS) in children were compared in a controlled prospective multi-centre 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. In a multicentre, randomised, prospective trial 89 patients (67 children and 22 adults) with the minimal change nephrotic syndrome were treated with three intravenous pulses of methylprednisolone followed by low dose oral prednisone for six months (group given methylprednisolone) or with high dose oral prednisone for four weeks followed by low dose oral prednisone for five months (control group). Five patients in the group given methylprednisolone and one in the control group did not respond initially. The time to response was shorter in children treated with methylprednisolone. No significant differences between the two groups were observed in the number of patients who relapsed or number of relapses per patient per year. Patients given methylprednisolone tended to relapse earlier than patients in the control group. Side effects related to treatment were significantly fewer in the group given methylprednisolone than in the control group. These data suggest that a short course of methylprednisolone pulses followed by low dose oral prednisone is only marginally less effective than a regimen of high dose oral steroids but can improve the ratio of risk to benefit associated with treatment of the minimal change 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. Relapses of nephrotic syndrome are usually treated with prednisolone, initially in three to four daily divided doses. The divided-dose regimen may cause poor patient compliance and greater adrenal suppression. In a prospective randomized controlled trial, we compared the efficacy of prednisolone in inducing remission of nephrotic syndrome, when given either as a single dose or in divided doses. Patients with steroid-responsive nephrotic syndrome with relapse were randomized to receive prednisolone 2 mg/kg per day, either as a single morning dose or in three divided doses for 2 weeks, followed by 1.5 mg/kg on every alternate day for 4 weeks. Parents tested the urine for protein daily until remission (nil proteinuria for 3 consecutive days). The duration between initiation of treatment and achievement of remission was recorded. Of 106 patients, 94 (47 each in single-dose and divided-dose groups) completed the study. The patients in the two groups were similar in relation to age, sex, number of relapses in the preceding year, and blood levels of creatinine, albumin, and cholesterol. The mean time for achievement of remission in the single- and divided-dose groups was 8.6 and 8.5 days, respectively (P = 0.94, power 96%). After 9 months' follow-up, there were no differences in the frequency of relapses and cumulative dose of prednisolone received in the two groups. The observations suggest that prednisolone administered in a single daily dose or in divided doses is equally effective in inducing remission in patients with relapsing nephrotic syndrome. Relapses are common in children with idiopathic nephrotic syndrome, and this prospective study looks into the possibility of decreasing the frequency of relapses in a selected group of such patients. The study includes 36 children with a steroid-dependent, relapsing nephrotic syndrome on a maintenance prednisone therapy of about 0.5 mg/kg every other day. They were prospectively divided into two groups with comparable age and sex distribution and the number of those who had previously received cyclophosphamide therapy. Group 1 patients were advised to take daily prednisone for 5 days, starting at the time of the onset of an upper respiratory tract infection (URI). No such advice was given to those in group 2, and they remained on alternate-day prednisone during URI. At the end of a 2-year follow-up period, the total number of relapses in group 1 was 40 with a mean of 2.2 +/- 0.87 per patient as compared with 99 with a mean of 5.5 +/- 1.33 per patient in group 2 (p = 0.04). We conclude that an increased maintenance prednisone during URI helps decrease significantly the number of relapses in those on alternate-day therapy.
                Copyright 2000 S. Karger AG, Basel Fifty-four children with steroid-responsive nephrotic syndrome relapsing within 6 months of their initial response were randomly allocated to receive two different regimens of prednisone therapy. The test regimen differed from the standard prednisone relapse regimen used by the International Study of Kidney Disease in Children in that the total dosage was about double, and the duration of daily therapy (8 weeks vs. a mean of 12 days) as well as the total duration of treatment (8 weeks vs. a mean of approximately 6 weeks) was longer. The proportion of patients relapsing during treatment was significantly smaller (8% vs. 40%) and the length of remission following treatment was significantly longer (3.27 vs. 1.48 months) in the test group. All patients in both groups relapsed by 8 months. During a period of approximately 6 months after this relapse, neither the frequency of relapses nor the mean number of days of proteinuria differed significantly. Opinions of participants in this multicenter trial varied concerning whether these statistically significant differences clinically justified exposing patients to the more intensive treatment regimen. However, all agreed that neither form of treatment was satisfactory in terms of preventing subsequent relapses. A long course of the initial prednisolone therapy has been shown to be more effective than standard-course therapy in reducing relapse rates in children with idiopathic nephrotic syndrome, but it is commonly accompanied by corticosteroid toxicities. There has been no study on prednisolone dosage for the effective treatment of nephrotic syndrome.
                Sixty-eight children (42 boys and 26 girls) with an initial attack of nephrotic syndrome were randomly allocated into two different long-course treatment groups. Patients in Group 1 received a daily prednisolone dose of 60 mg/m2 for six weeks, followed by an alternate-day dose of 40 mg/m2 for six weeks. Patients in Group 2 had a daily dose of 40 mg/m2 instead of 60 mg/m2.
                Four children in each group did not respond within six weeks. Group 1 was associated with a significantly earlier response but more frequent corticosteroid toxicities than Group 2. Boys in Group 1 had a higher rate of sustained remission than boys in Group 2 (P = 0.0073), especially boys four years old or more (P = 0.0027), but girls did not show a significant difference (P = 0.863). Boys four years old or more in Group 1 had a course of frequent relapsing less often than those in Group 2 (2 of 13 vs. 6 of 8, P = 0.0075).
                These findings indicate that efficient prednisolone doses may vary between sexes and ages, and that a higher initial prednisolone therapy may be of greater benefit to older boys. Long-course prednisolone regimens have been shown to be more effective than short-course regimens in sustaining remission of nephrotic syndrome in children. However, the most beneficial approach among the long-course regimens remains unknown.
                Seventy-three children with new-onset nephrotic syndrome were allocated at random to the two long-course regimens and followed up for 2 years. Group A was administered prednisolone at a daily dose of 60 mg/m2 for 6 weeks, followed by an alternate-day dose of 40 mg/m2 for 6 weeks (the long daily regimen). Group B was administered the same daily dose for 4 weeks, followed by an alternate-day dose of 60 mg/m2 for 4 weeks, and doses were tapered by 10 mg/m2 every 4 weeks (the long alternate-day regimen).
                Group B had a lower incidence of corticosteroid toxicities than group A during the initial treatment. Kaplan-Meier analysis of the sustained remission rate of the two treatment groups showed a marginally significant difference (P = 0.069) and showed a significant difference when patients were stratified for age of disease onset (P = 0.048). In a subgroup of younger children (<4 years at onset), group B had a greater rate of sustained remission (P < 0.01) and fewer children with frequent relapses (P < 0.05) than group A, whereas in older children (> or =4 years at onset), both groups had similar good sustained remission rates.
                These findings collectively indicate that the long alternate-day regimen may be more beneficial, with less corticosteroid toxicities, than the long daily regimen, and children with younger age at disease onset may be susceptible to relapse and especially benefit from the long alternate-day regimen for sustaining remission of the disease.
Children in their first episode of SSNS should be treated for at least three months with an increase in benefit for up to seven months of treatment. For a baseline risk for relapse following the first episode of 60% with two months of therapy, daily prednisone or prednisolone given for four weeks followed by alternate-day therapy for six months would reduce the number of children relapsing by 33%.