***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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    Input: 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 To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy , we compared two regimens based on a 6-mo treatment , alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide .  Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were r and omized to be given methylprednisolone ( 1 g intravenously for 3 consecutive days followed by oral methylprednisolone , 0.4 mg/kg per d for 27 d ) alternated every other month either with chlorambucil ( 0.2 mg/kg per d for 30 d ) or cyclophosphamide ( 2.5 mg/kg per d for 30 d ) . The whole treatment lasted 6 mo ; 3 mo with corticosteroids and 3 mo with one cytotoxic drug . Among 87 patients followed for at least 1 yr , 36 of 44 ( 82 % ; 95 % confidence interval [ CI ] , 67.3 to 91.8 % ) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome , versus 40 of 43 ( 93 % ; 95 % CI , 80.9 to 98.5 % ) assigned to methylprednisolone and cyclophosphamide ( P = 0.116 ) . Of patients who attained remission of the nephrotic syndrome , 11 of 36 in the chlorambucil group ( 30.5 % ) and 10 of 40 in the cyclophosphamide group ( 25 % ) had a relapse of the nephrotic syndrome between 6 and 30 mo . The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups ( P < 0.01 ) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr . Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects . Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster . One patient per group developed cancer . It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr BACKGROUND We conducted a pilot trial to compare the effectiveness and safety of 2 different treatments in patients with membranous nephropathy and nephrotic syndrome . METHODS To vali date the hypothesis that the 2 treatments were equivalent , patients with biopsy-proven membranous nephropathy and nephrotic syndrome were r and omly assigned to methylprednisolone alternated with a cytotoxic drug every other month for 6 months ( group A ) or to intramuscular synthetic adrenocorticotropic hormone administered twice a week for 1 year ( group B ) . RESULTS The primary outcome measure is cumulative number of remissions as a first event . Fifteen of 16 patients in group A and 14 of 16 patients in group B entered complete or partial remission as a first event . After a median follow-up of 24 months ( interquartile range , 15 to 25 months ) , there were 4 complete remissions and 8 partial remissions in group A versus 8 complete remissions and 6 partial remissions in group B. Median proteinuria decreased from protein of 5.1 g/d ( interquartile range , 4.0 to 7.3 g/d ) to 2.1 g/d ( interquartile range , 0.4 to 3.8 g/d ; P = 0.004 ) in group A and 6.0 g/d ( interquartile range , 4.4 to 8.5 g/d ) to 0.3 g/d ( interquartile range , 0.2 to 1.9 g/d ; P = 0.049 ) in group B. Two patients from each group interrupted treatment because of side effects or inefficacy . CONCLUSION Most nephrotic patients with membranous nephropathy responded to either treatment . Proteinuria was significantly decreased with both methylprednisolone and cytotoxic agents or prolonged administration of synthetic adrenocorticotropic hormone , without significant differences between these 2 therapies Controlled trial of cyclophosphamide in idiopathic membranous nephropathy . We evaluated cyclophosphamide treatment in a controlled prospect i ve study of 22 adult patients with clinical ly and histologically defined idiopathic membranous nephropathy . By r and om assignment , 11 patients received no drug and 11 patients received cyclophosphamide orally , 1.5 to 2.5 mg/kg/day ( mean , 1.8 ) , for one year . Before treatment , the two groups were similar in age and sex distributions , duration of illness , blood pressure , degree of proteinuria , renal function and histologic staging . After treatment , a downward trend in proteinuria was noted , with no significant difference in the quantity and rate of decrease between groups . Renal function ( C in and C PAH ) was stable in all patients , with no difference between groups . On comparing pretreatment and one-year renal biopsy specimens in eight patients in each group , regardless of treatment or clinical outcome , the appearance of the renal lesions remained the same or progressed in terms of basement membrane thickening and incorporation of subepithelial deposits , and immunofluorescence with IgG and C3 remained positive in glomerular capillaries . Cyclophosphamide dosage was decreased in five patients because of recurrent leukopenia ; no other major toxicity was observed . Beyond one year of treatment , renal function has decreased in two of eight patients in the no-drug group and in one of seven patients in the cyclophosphamide-treated group . We conclude that treatment with cyclophosphamide for one year did not have a favorable effect on proteinuria , renal function or morphologic aspects of the glomerular lesion . Essai controle du cyclophosphamide dans la nephropathie membraneuse idiopathique . Nous avons evalue le traitement par le cyclophosphamide dans une etude prospect i ve controlee de 22 malades adultes atteints de nephropathie membraneuse idiopathique cliniquement et anatomiquement definie . Au hasard , onze malade n'ont recu aucun traitement et onze autres ont eu du cyclophosphamide par voie orale a raison de 1,5 a 2,5 mg/kg par jour ( 1,8 en moyenne ) pendant un an . Avant le traitement les deux groupes etaient semblables en distribution d'âge et de sexe , duree de la maladie , pression arterielle , importance de la proteinurie , fonction renale et etat histologique . Apres traitement , une tendance a la diminution de la proteinurie a ete observee sans difference significative entre les groupes dans le debit de proteine ou la vitesse de diminution . La fonction renale ( C in et C PAH ) etait stable chez tous les malades , sans difference entre les groupes . La comparaison des biopsies avant traitement et apres un an chez huit malades de chaque groupe , independamment du traitement ou de l'evolution clinique , a montre que les lesions renales sont restees les memes ou ont progresse , sous la forme d'un epaississement de la membrane basale et de l'incorporation de depots sous-epitheliaux , et que l'immunofluorescence avec IgG et C3 reste positive dans les capillaires glomerulaires . La posologie du  cyclophosphamide  a ete diminuee chez cinq malades en raison d'une leucopenie recidivante ; aucune autre toxicite majeure n'a ete observee . Au-dela d'un an de traitement , la fonction renale a diminue chez deux des huit malades du groupe ne recevant pas de medicament et chez l'un des sept malades du groupe traite par le cyclophosphamide . Nous concluons que le traitement par le cyclophosphamide pendant un an n'a pas eu d'effet favorable sur la proteinurie , la fonction renale ou les lesions histologiques glomerulaires BACKGROUND Retrospective and anecdotal data suggest that mycophenolate mofetil ( MMF ) might be effective when given as rescue therapy for membranous nephropathy ( MN ) . Prospect i ve controlled data on MMF and prednisolone as primary therapy are lacking . METHODS A prospect i ve , r and omized , controlled , open-label study was performed to investigate the efficacy and tolerability of MMF and prednisolone as primary treatment in MN with nephrotic syndrome .  MMF and prednisolone given for 6 months was compared against a modified Ponticelli regimen in 20 patients , with follow up of 15 months . RESULTS MMF with prednisolone and the comparative immunosuppressive regimen showed similar efficacy in proteinuria reduction , despite a lower cumulative prednisolone dose in the MMF group ( 3.80 + /- 0.28 vs 9.93 + /- 0.25 g , P < 0.001 ) . Remission ( composite of ' complete ' and ' partial ' ) rates were 63.6 % and 66.7 % in the MMF group and control group , respectively ( P = 1.000 ) . Serum creatinine and creatinine clearance remained stable during follow up . Cumulative relapse rate was 23.1 % at 2 years . Chlorambucil result ed in more leucopenia compared with MMF . CONCLUSION Data from this pilot study indicate that more than 60 % of patients with MN and nephrotic syndrome respond to combined MMF and prednisolone treatment , and suggest potential benefits of MMF as being steroid-sparing and having less adverse effects compared with other commonly used cytotoxic agents BACKGROUND The current treatment regimes for patients with nephrotic syndrome due to idiopathic membranous nephropathy ( MN ) and focal segmental glomerulosclerosis ( FSGS ) are based on steroids and /or cytotoxic agents . Data on the effect of mycophenolate mofetil ( MMF ) for these conditions are scarce and confounding . METHODS We compared the efficacy of an MMF-based therapy with st and ard therapies in inducing remission in adult nephrotics with MN and FSGS in a r and omized pilot study . MMF was given at 2 g/day for 6 months along with prednisolone at 0.5 mg/kg/day for 2 - 3 months . Conventional therapy was prednisolone 1 mg/kg/day for 3 - 6 months for FSGS and alternating monthly cycles of steroids and cyclophosphamide for 6 months for MN . The primary end point was change in urinary protein/creatinine ratio . RESULTS A total of 54 patients ( 21 MN and 33 FSGS ) were recruited ; 28 were r and omized to receive MMF ( group A ) and 26 were on conventional treatment ( group B ) . There was no difference in the proportion of patients achieving remission in two groups ( 64 and 80 % in MN and 70 and 69 % in FSGS ) . The frequency of relapses and incidence of infections was also similar . FSGS patients in group A achieved remission faster and received a lower cumulative steroid dose . CONCLUSIONS A 6-month treatment with MMF is as effective as the conventional treatment for primary treatment of MN and F 
    Output:
    
Cyclosporine and mycophenolate mofetil failed to show superiority over alkylating agents .
Tacrolimus and adrenocorticotropic hormone significantly reduced proteinuria .
CONCLUSIONS Alkylating agents plus corticosteroids had long-term and short-term benefits for adult IMN , but result ed in more withdrawals or hospitalizations