***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 
    ***DOCUMENTATION*** 
    ***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 Background A previous double-blind 24-week clinical trial of mizoribine ( MZ ) vs placebo in steroid-resistant primary nephrotic syndrome ( SRPNS ) showed that MZ was more effective than placebo in reducing the rate of deterioration of renal function . The present study was conducted to evaluate the efficacy and safety of MZ in patients with SRPNS after 2 years ’ treatment . Methods A multicenter r and omized open-label controlled trial in patients with SRPNS was conducted as a 2-year prospect i ve postmarketing study . Results There was a significant imbalance in the baseline serum albumin level ( s-Alb ) between the conventional therapy ( CT ) and MZ onlay therapy groups . Early dropouts were more frequent in the subset of patients in the CT group having a baseline s-Alb ≤3 g/dl . Therefore , the primary analysis ( urinary protein level (UP)-improving effect ) was performed using a mixed-effects model , with stratification according to the baseline s-Alb value . The analysis revealed that , in the subset of 34 patients with membranous nephropathy ( MN ) within the stratum of patients with baseline s-Alb ≤3 g/dl ( n = 52 ) , the rate of change ( slope of change in the UP level/month ) , in terms of the log ( UP+0.2 ) , was −0.0577 in those allocated to the MZ group and −0.0227 in those allocated to the CT group ( P = 0.058 ) . In the stratum of patients with a baseline s-Alb > 3 g/dl ( n = 97 ) , there were no significant differences in the UP between the two treatment groups . Hence , MZ onlay therapy was not considered to be efficacious in this group of patients . No serious adverse reactions to the drug were observed . Conclusions The present study yielded significant results , in that it suggested the possibility that long-term MZ therapy may afford further reduction of the UP , in addition to that obtained following CT , in particular , in MN patients in a severe nephrotic state Background The lack of adequate r and omized clinical trials ( RCT ) has hindered identification of new therapies that are safe and effective for patients with primary focal segmental glomerulosclerosis ( FSGS ) , especially in patients who fail to respond to corticosteroids and immunosuppressive therapies . Recent basic science advances have led to development of alternative treatments that specifically target aberrant pathways of fibrosis which are relevant to disease progression in FSGS . There is a need for a flexible Phase II study design which will test such novel antifibrotic strategies in order to identify agents suitable for phase III testing . Methods / Design The Novel Therapies for Resistant Focal Segmental Glomerulosclerosis ( FONT ) project is a multicenter Phase I/II RCT design ed to investigate the potential efficacy of novel therapies for resistant FSGS . Adalimumab and galactose will be evaluated against conservative therapy consisting of the combination of lisinopril , losartan and atorvastatin . The sample size is defined to assure that if one of the treatments has a superior response rate compared to that of the other treatments , it will be selected with high probability for further evaluation . Comparison of primary and secondary endpoints in each study arm will enable a choice to be made of which treatments are worthy of further study in future Phase III RCT . Discussion This report highlights the key features of the FONT II RCT including the two-step outcome analysis that will expedite achievement of the study objectives . The proposed phase II study design will help to identify promising agents for further testing while excluding ineffective agents . This staged approach can help to prevent large expenditures on unworthy therapeutic agents in the management of serious but rare kidney diseasesTrial Registration Clinical Trials.gov , 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 Background Patients with resistant focal segmental glomerulosclerosis ( FSGS ) who are unresponsive to corticosteroids and other immunosuppressive agents are at very high risk of progression to end stage kidney disease . In the absence of curative treatment , current therapy centers on renoprotective interventions that reduce proteinuria and fibrosis . The FONT ( Novel Therapies for Resistant FSGS ) Phase II clinical trial ( NCT00814255 , Registration date December 22 , 2008 ) was design ed to assess the efficacy of adalimumab and galactose compared to st and ard medical therapy which was comprised of lisinopril , losartan , and atorvastatin . Methods Key eligibility criteria were biopsy confirmed primary FSGS or documentation of a causative genetic mutation , urine protein : creatinine ratio > 1.0 g/g , and estimated glomerular filtration rate ( eGFR ) > 40 ml/min/1.73 m2 . The experimental treatments – adalimumab , galactose , st and ard medical therapy-- were administered for 26 weeks . The primary endpoint was a 50 % reduction in proteinuria with stable eGFR . Results Thirty-two subjects were screened and 21 were assigned to one of the three study arms . While none of the adalimumab-treated subjects achieved the primary outcome , 2 subjects in the galactose and 2 in the st and ard medical therapy arm had a 50 % reduction in proteinuria without a decline in eGFR . The proteinuria response did not correlate with serial changes in the serum glomerular permeability activity measured by the Palb assay or soluble urokinase plasminogen activator receptor ( suPAR ) . There were no serious adverse effects related to treatments in the study . Conclusions Recruitment into this trial that addressed patients with resistant FSGS fell short of the enrollment goal . Our findings suggest that future studies of novel therapies for rare glomerular diseases such as FSGS may benefit from enrollment of patients earlier in the course of their disease . In addition , better identification of patients who are likely to respond to a new treatment based on biomarkers suggesting involvement of the disease pathway targeted by the experimental agent may reduce the required sample size and increase the likelihood of a favorable outcome In a controlled trial , symptomatic treatment alone , or 12 weeks of cyclophosphamide or azathioprine were compared in Nigerian children with nephrotic syndrome ( mainly quartan malarial nephropathy ) and poorly selective proteinuria .  Full remission in 2 patients in each of the two groups treated with drugs , and diminution of proteinuria in most patients in the cyclophosphamide group showed possible evidence of benefit . Infections during treatment were significantly more common in the drug-treated groups but were controllable . Mortality from renal failure in the 2nd year after treatment was significantly greater in the azathioprine-treated group than in the other two , suggesting that the drug may have exacerbated the nephritis . The 5-year survival rate was similar in the cyclophosphamide and the control group OBJECTIVE To compare the efficacy ( maintenance of remission ) , safety and tolerability of cyclosporin ( CsA ) with those of cyclophosphamide in patients with steroid-dependent or frequently relapsing nephrotic syndrome ( NS ) . DESIGN Open , prospect i ve , r and omized , multicentre , controlled study for parallel groups , stratified for adults and children . The setting was in nephrological departments in Italy . SUBJECTS AND INTERVENTIONS Seventy-three patients with steroid-sensitive idiopathic NS admitted to the study were r and omly assigned to cyclophosphamide ( 2.5 mg/kg/day ) for 8 weeks or CsA ( 5 mg/kg/day in adults , 6 mg/kg/day in children ) for 9 months , tapered off by 25 % every month until complete discontinuation at month 12 . Seven patients lost to follow up were not considered in the analysis . The remaining 66 patients were followed up for 3 - 24 months after r and omization . MAIN OUTCOME MEASURES Relapse-free survival ; number of N.S. relapses/patient/year ; cumulative dose of prednisone/patient ; laboratory investigations ( kidney and liver functions , haematological parameters ) ; incidence of adverse events . RESULTS At month 9 , 26 of 35 CsA-treated patients were still in complete remission and a further five patients were in partial remission ; 18 of 28 cyclophosphamide-treated patients were in complete remission , and one in partial remission ( P = NS ) . No difference between adults and children was seen with either treatment . The risk of relapse was similar between frequent relapsers ( 19 of 22 ) and steroid-dependent patients ( 8 of 14 ) given CsA , and those given cyclophosphamide ( 5 of 15 and 6 of 15 ) . The mean number of relapses per year and the mean dose of prednisone per year were significantly less ( P < 0.001 ) in both groups for the experimental year than for the year before r and omization . At 2 years , 25 % of the patients given CsA ( 50 % adults and 20 % children ) and 63 % of those given cyclophosphamide ( 40 % adults and 68 % children ) had not had any relapse of NS . Tolerance to the two drugs was generally good . The  CsA-related side-effects were mild and disappeared after drug discontinuation . CONCLUSIONS This study shows that both treatments are effective and well tolerated ; more patients given cyclophosphamide had stable remissions BACKGROUND Patients with primary focal segmental glomerulosclerosis ( FSGS ) resistant to current treatment regimens are at high risk of progression to end-stage kidney disease . Antifibrotic agents , such as tumor necrosis factor alpha antagonists , are a promising strategy to slow or halt the decline in renal function , based on pre clinical and clinical data . STUDY DESIGN Phase 1 clinical trial to assess the pharmacokinetics , tolerability , and safety of adalimumab , a human monoclonal antibody to tumor necrosis factor alpha . SETTING & PARTICIPANTS 10 patients ( 4 male and 6 female ) aged 16.8 + /- 9.0 years with an estimated glomerular filtration rate of 105 + /- 50 mL/min/1.73 m(2 ) were studied . INTERVENTION Adalimumab , 24 mg/m(2 ) , every 14 days for 16 weeks ( total , 9 doses ) . OUTCOMES Pharm 
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Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission .
AUTHORS ' CONCLUSIONS To date RCTs have demonstrated that calcineurin inhibitors increase the likelihood of complete or partial remission compared with placebo/no treatment or cyclophosphamide .