***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: Sixty children , with biopsy diagnosed focal segmental glomerulosclerosis ( FSGS ) and with unremitting nephrotic syndrome despite intensive therapy with adrenocortical steroids  , were r and omly allocated into a clinical trial comparing prednisone , 40 mg/m2 on alternate days for a period of 12 months ( control group ) , with the same prednisone regimen plus a 90-day course of daily cyclophosphamide , 2.5 mg/kg in a single morning dose ( experimental group ) . One-quarter of the children in each group had complete resolution of proteinuria . The proportions of children with increased , unchanged , and decreased proteinuria by the end of the study were the same in the two groups . Treatment fialure was defined as an increase in serum creatinine of 30 % or more or greater than 0.4 mg/dl , or onset of renal failure . Treatment failure occurred in 36 % of the control group and 57 % of the experimental group ( P>0.1 ) . Five patients died during the trial , 3 in the experimental group and 2 in the control group . A Kaplan-Meier survival analysis revealed no significant differences between the two groups . Cyclophosphamide therapy for children with  steroid-resistant FSGS  is not recommended There is no generally accepted treatment for primary focal segmental glomerulosclerosis ( FSGS ) .  Steroids alone and steroids plus cyclophosphamide can be expected to induce a remission of the proteinuria in only 27 % of patients . Probably the majority of FSGS patients will reach ESRD over the extended course of their disease . In addition to the work presented in this study , there have been many reports of the potential effectiveness of cyclosporine ( CSA ) on reducing the proteinuria of FSGS . This study was undertaken to test the efficacy and safety of a 6-month course of CSA in a double-blinded , prospect ively r and omized , placebo-controlled trial in children with corticosteroid-resistant FSGS . The potential inhibitory effect of hypercholesterolemia on the proteinuria-reducing actions of CSA was also assessed . Twenty-five patients with FSGS were r and omized to receive either placebo or CSA for 6 months . Twelve of the 12 patients that received CSA experienced a diminution of their proteinuria as opposed to only two of the 12 placebo-treated patients . Proteinuria was significantly reduced from 151.7 + /- 162.4 mg/kg per 24 h at Week 0 to 36.9 + /- 42.3 at the end of the study in the group that received CSA ( P < 0.05 ) . There was no significant change in the proteinuria of the patients in the  placebo  group . A significant correlation between the percentage change of proteinuria over the 6 months of the study and the pre study serum cholesterol levels ( r = 0.79 , P < 0.05 ) was seen in the CSA group . A partial correlation analysis controlling for the effects of serum cholesterol uncovered a significant relationship between average CSA level and proteinuria change ( r = -0.76 , P < 0.05 ) . The fractional decline in GFR over the course of the study was not significantly different between the CSA and placebo-treated groups . In conclusion ,  CSA  reduces proteinuria , increases serum albumin levels , and can be expected , therefore , to reduce the symptoms of nephrotic syndrome . Hypercholesterolemia antagonizes this effect of CSA First line immunosuppressive treatment in steroid-resistant nephrotic syndrome in children is still open to discussion . We conducted a controlled multicentre r and omized open label trial to test the efficacy and safety of cyclosporin A ( CSA ) versus cyclophosphamide pulses ( CPH ) in the initial therapy of children with newly diagnosed primary steroid-resistant nephrotic syndrome and histologically proven minimal change disease , focal segmental glomerulosclerosis or mesangial hypercellularity . Patients in the CSA group ( n = 15 ) were initially treated with 150 mg/m2 CSA orally to achieve trough levels of 120–180 ng/ml , while patients in the CPH group ( n = 17 ) received CPH pulses ( 500 mg/m2 per month intravenous ) . All patients were on alternate prednisone therapy .  Patients with proteinuria > 40 mg/m2 per hour at 12 weeks of therapy were allocated to a non-responder protocol with high-dose CSA therapy or methylprednisolone pulses . At week 12 , nine of the 15 ( 60 % ) CSA patients showed at least partial remission , evidence s by a reduction of proteinuria < 40 mg/h per m2 . In contrast , three of the 17 ( 17 % ) CPH patients responded ( p < 0.05 , intention-to-treat ) . Given these results , the study was stopped , in accordance with the protocol . After 24 weeks , complete remission was reached by two of the 15 ( 13 % ) CSA and one of the 17 ( 5 % ) CPH patients ( p = n.s . ) . Partial remission was achieved by seven of the 15 ( 46 % ) CSA and two of the 15 ( 11 % ) CPH patients ( p < 0.05 ) . Five patients in the CSA group and 14 patients in the CPH group were withdrawn from the study , most of them during the non-responder protocol . The number of adverse events was comparable between both groups . We conclude that CSA is more effective than CPH in inducing at least partial remission in steroid-resistant nephrotic syndrome in children We compared , in a r and omized controlled trial , the efficacy of a regimen based on intravenous ( i.v . ) cyclophosphamide therapy with a combination of i.v . dexamethasone and oral cyclophosphamide therapy in inducing remission in patients with steroid-resistant nephrotic syndrome ( SRNS ) . During April 2001 to December 2003 , 52 consecutive patients with idiopathic SRNS , normal renal function and renal histology findings showing minimal change disease , focal segmental glomerulosclerosis or mesangioproliferative glomerulonephritis were enrolled into the study . Patients in group I received i.v . injection of cyclophosphamide once a month for 6 months and prednisolone on alternate days . Those in group II received i.v . treatment with dexamethasone ( initially on alternate days , later fortnightly and monthly ; total 14 doses ) , oral cyclophosphamide therapy ( for 3 months ) and prednisolone on alternate days . Data from 49 patients ( 26 in group I , 23 in group II ) were analyzed ; their clinical and biochemical features were similar at inclusion . Following treatment , complete remission was seen in 53.8 % and 47.8 % patients in groups I and II , respectively ( P = 0.6 ) . Long-term follow up showed favorable outcome in 14 ( 53.8 % ) patients in group I , and 9 ( 39.1 % ) in group II . Chief adverse effects , including cushingoid features and serious infections , were similar in both groups . Patients receiving i.v . dexamethasone therapy commonly showed hypertension and hypokalemia , while vomiting and reversible alopecia occurred in those receiving i.v . treatment with cyclophosphamide . In patients with SRNS , the efficacy of treatment intravenously with cyclophosphamide and orally with prednisolone was similar to the combination of dexamethasone intravenously , orally administered cyclophosphamide and prednisolone The treatment of steroid-resistant minimal change nephrotic syndrome ( MCNS ) continues to pose a therapeutic challenge . We conducted a r and omised prospect i ve controlled trial to evaluate the efficacy of IV cyclophosphamide compared with oral cyclophosphamide in 13 children with biopsy-proven steroid-resistant MCNS . All 7 patients receiving IV cyclophosphamide achieved remission ; this was sustained in 4 patients , while 3 relapsed . However , even these 3 patients subsequently became steroid sensitive . Of the 6 patients who received oral cyclophosphamide , 2 dropped out , 1 responded and 3 children continued to remain steroid resistant . The children who received IV cyclophosphamide had more sustained remissions , longer periods without proteinuria and fewer significant side effects ; this was achieved at a lower cumulative dose One hundred and fourteen children with primary nephrotic syndrome were followed up prospect ively for periods of between 5 and 14 years . Urine sample s 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 BACKGROUND To examine whether tacrolimus is more effective and safe than cyclosporine ( CsA ) in inducing remission in patients with steroid-resistant nephrotic syndrome ( SRNS ) . STUDY DESIGN R and omized controlled trial , nonblind , parallel group . SETTING S & PARTICIPANTS Tertiary-care hospital ; 41 consecutive patients with idiopathic SRNS , estimated glomerular filtration rate greater than 60 mL/min/1.73 m(2 ) , and histological characteristics showing minimal change disease , focal segmental glomerulosclerosis , or mesangioproliferative glomerulonephritis were r and omly assigned to treatment with  tacrolimus ( n = 21 ) or CsA ( n = 20 ) . INTERVENTION Tacrolimus ( 0.1 to 0.2 mg/kg/d ) or CsA ( 5 to 6 mg/kg/d ) for 1 year ; cotreatment with alternate-day prednisolone and enalapril . OUTCOMES Patients achieving complete remission ( urinary protein-creatinine ratio < 0.2 g/g and serum albumin > or = 2.5 g/dL ) or partial remission ( urinary protein-creatinine ratio , 0.2 to 2 g/g , and serum albumin > or = 2.5 g/dL ) at 6 and 12 months ; time to remission ; proportion with relapses ; side effects . RESULTS No patient was lost to follow-up . After 6 months of therapy , remission occurred in 18 ( 85.7 % ) and 16 patients ( 80 % ) treated with tacrolimus and CsA , respectively ( relative risk [ RR ] , 1.07 ; 95 % confidence interval [ CI ] , 0.81 to 1.41 ) . Rates of remission at 12 months were also similar ( RR , 1.14 ; 95 % CI , 0.84 to 1.55 ) . The proportion of patients who experienced relapse was significantly greater in those receiving CsA compared with tacrolimus ( RR , 4.5 ; 95 % CI , 1.1 to 18.2 ; P = 0.01 ) . The decrease in blood cholesterol levels was greater with tacrolimus compared with CsA ( difference in mean values , 45.1 mg/dL ; 95 % CI , 19.1 to 71.2 ) . Persistent nephrotoxicity necessitating stoppage of medicine was seen in 4.7 % and 10 % patients , respectively . Cosmetic side effects ( hypertrichosis and gum hypertrophy ) were significantly more frequent in CsA-treated patients ( P < 0.001 ) . LIMITATIONS Single-center study , small sample size , and short duration of follow-up . CONCLUSIONS Tacrolimus or CsA in combination with low-dose steroids show similar efficacy in inducing remission in patients with SRNS . Therapy with tacrolimus is a promising alternative to CsA in view of the lower risk of relapses and lack of cosmetic side effects AIM The treatment strategy for steroid-resistant nephrotic syndrome remains uncertain at present , especially in those with calcineurin inhibitor resistance or intolerance . To date , few studies have been published using multiple combination therapy of immunosuppressive reagents for children with calcineurin inhibitor-resistant or -intolerant nephrotic syndrome . METHODS Eighteen consecutive children with steroid- and tacrolimus (TAC)-resistant ( n = 10 ) or TAC-sensitive but frequent relapsing nephrotic syndrome ( n = 8) were r and omly recruited in the present study . All of them received further triple-combination therapy by cyclophosphamide ( CTX , n = 6 ) , mycophenolate mofetil ( MMF , n = 5 ) or leflunomide ( LEF , n = 7 ) . Their clinical data were collected and efficacy of triple-combination therapy was evaluated . RESULTS Compared with previous double-combination therapy of prednisone ( Pre ) and TAC , the short-term remission rate in all 18 patients was significantly improved after the triple-combination therapy , while the frequent relapse rate in the following 12 months was also significantly decreased . Among three different subgroups with CTX 
    Output:
    
RESULTS A meta- analysis of 18 RCTs showed that tacrolimus was more efficacious for achieving CR than intravenous ( i.v .
) cyclophosphamide , mycophenolate mofetil ( MMF ) , oral cyclophosphamide , leflunomide , chlorambucil , azathioprine , and plaebo/nontreatment ( P/NT ) , and more efficacious than i.v .
cyclophosphamide , oral cyclophosphamide , and P/NT in terms of TR outcomes .
Cyclosporin was associated with a greater CR rate than i.v .
cyclophosphamide , MMF , oral cyclophosphamide , chlorambucil , azathioprine , or P/NT , and associated with a greater TR rate than i.v .
cyclophosphamide , oral cyclophosphamide , or P/NT .
MMF was found to be more efficacious than i.v .
cyclophosphamide and oral cyclophosphamide in terms of TR .
Tacrolimus and cyclosporine may be preferred initial treatments for children with SRNS .
MMF may be another option for this patient population .