***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: 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 In this retrospective non-r and omized study we review ed the outcome for 41 patients with membranous nephropathy older than 65 years at onset and followed for at least 1 year . Twelve of the patients never received any specific treatment ( group A ) , 15 were treated with a 6-month course of methylprednisolone alternated to chlorambucil every other month ( group B ) , and 14 received corticosteroids alone for 3 - 12 months ( group C ) . At the end of a mean follow-up of 92 + /- 61 months in group A , 53 + /- 35 in group B , and 38 + /- 25 in group C there were significantly more remissions of nephrotic syndrome in group B than in group A ( P = 0.035 ) or in group C ( P = 0.010 ) . Moreover patients in group B spent a significantly longer period without nephrotic syndrome than patients in group A ( P = 0.000 ) and C ( P = 0.000 ) . Three patients in group A and one in group B died . During the follow-up six patients of group A , two of group B , and five of group C developed renal function deterioration . In patients followed for at least 5 years the mean plasma creatinine increased from a basal of 112 + /- 29 to 239 + /- 287 mumol/l at the 5th year in group A and from 113 + /- 14 to 124 + /- 30 mumol/l in group B. The mean urine protein excretion remained unchanged in group A ( basal 4.6 + /- 2.3 versus 4.8 + /- 5.7 g/day at 5 years ) while it decreased in group B ( from a basal of 6.8 + /- 3.5 to 1.1 + /- 0.4 g/day at 5 years ) . ( ABSTRACT TRUNCATED AT 250 WORDS Patients with various forms of glomerulonephritis , but excluding those with minimal glomerular changes , were admitted to a controlled trial of a regimen which combined azathioprine in a dosage of 2·5 mg/kg/day with prednisone in a dosage of 20 mg/day ( adults ) or 0·5 mg/kg/day ( children ) . Of 149 patients included , 32 of them under the age of 15 , 72 were r and omly allocated to the “ treatment ” group and 77 to the “ control ” group . There was no evidence of benefit from the treatment group as a whole ; and the mortality was in fact higher in the treated group Patients with membranous glomerulonephritis ( MGN ) , impaired renal function and the nephrotic syndrome are at high risk of developing renal failure . Twenty-six such patients were studied with serum creatinine concentrations exceeding 135 microM , and 24-hour urine protein excretion of at least 3.5 g/day to determine the potential benefit of cyclophosphamide therapy . Cyclophosphamide ( mean 1.5 mg/kg/day ) was given to nine patients for 23 + /- 4 months . These patients were compared with 17 concurrent controls . The two groups did not differ in clinical or laboratory features at the time of biopsy or start of treatment or its equivalent . Six of the nine  cyclophosphamide  treated patients and 15 of the 17 controls had received prednisone therapy . The total follow-up was 49 + /- 10 months in the treated group and 50 + /- 6 months in the controls . At last observation , serum creatinine values exceeded 400 microM in eight controls ( 4 on dialysis ) and in none of the treated patients . The mean serum creatinine level was significantly lower ( P less than 0.02 ) in the treated group ( 173 + /- 24 microM ) than in controls ( 433 + /- 71 0.02 ) in the treated group ( 173 + /- 24 microM ) than in controls ( 433 + /- 71 microM ) . The mean serum albumin level and 24-hour urine protein excretion both improved significantly with treatment as compared with controls . There were four complete remissions , five partial remissions and no patient with persistent nephrotic syndrome after treatment . In the controls , there were no complete remissions , six partial remissions and 11 patients had persistent nephrotic syndrome ( P less than 0.001 ) . Thus , cyclophosphamide therapy appears to be of benefit in patients with MGN , the nephrotic syndrome and impaired renal function Because of the high rate of spontaneous remission , treatment of membranous nephropathy with prednisolone and chlorambucil is still controversial . The aim of this study was to give this therapy only to those patients at risk of developing renal insufficiency and to test the efficacy of a low-dose therapeutic regimen . Seventeen patients with more than 10 g protein excretion per day ( mean 16.9 ) and /or a deterioration in renal function ( mean serum creatinine , 162 μmol/l ) were included . Serum total protein , serum lipids , proteinuria , serum creatinine , and blood pressure were measured , along with the diuretic and antihypertensive medication . The observation time before the start of treatment was 27 ± 27 months . Steroids were given during months 1 , 3 , and 5 ( methylprednisolone 3 × 500 mg intravenously ) prednisolone 0.5 mg/kgBW daily per os for 1 week , then tapered by 0.1 mg/kg BW/week for 1 month . Chlorambucil was given during months 2 , 4 , and 6 at a dose of 0.12 mg/kgBW daily . At the end of treatment proteinuria had significantly decreased ( mean of all patients , 7.8 ± 1.4 g/d ) in all patients . Six months after the end of treatment proteinuria was significantly lower than at baseline in 14 of 17 patients . Hypoproteinemia and hyperlipidemia had improved ; diuretic and antihypertensive medication were reduced . Elevated serum creatinine decreased in 7 of 9 patients ( pretreatment , 227 ± 39 μmol/1 ; 6 months , 176 ± 28 μmol/l ) . Nonresponders with respect to serum creatinine responded with respect to proteinuria . Regarding adverse effects , two patients complained of dyspepsia while taking steroids ; during chlorambucil treatment two patients experienced nausea and lack of appetite , and one developed leukopenia ( 1600/μl ) . Chlorambucil was stopped and cell counts normalized 2 weeks later . We conclude that low-dose prednisolone/chlorambucil is both safe and efficient in the majority of patients with severe membranous nephropathy 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 
    Output:
    
In patients with MN , nephrotic syndrome and normal renal function , methylprednisolone and chlorambucil or cyclophosphamide for 6 months alternately increase the probability of nephritic syndrome remission ( evidence from SR ) and long-term renal protection ( evidence from RCT ) .
Other drugs ( ACTH and cyclosporine ) are associated with nephrotic syndrome remission , but there is no evidence of significant effects on renal function ( evidence from RCT ) .
In patients with impaired renal function , association of corticosteroids and cytotoxic agents is proven to cause a short-term delay of renal damage progression , even though benefits are counterbalanced by complications ( evidence from RCT ) .