***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: A key issue in the analysis of outcome trials is the adjustment for baseline covariates that influence the primary outcome . Imbalance of an important covariate between treatment groups at baseline is of considerable concern if one treatment group is favored over another with respect to the hypothesis testing outcome . With the use of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan ( RENAAL ) study data base as an example , the influence of baseline proteinuria on the primary composite endpoint , ESRD , and ESRD or death after adjusting for baseline proteinuria as a continuous covariate was examined . Increasing baseline proteinuria was associated with increased risk for renal events , confirming that proteinuria is an important covariate for renal outcomes . When the r and omization was stratified according proteinuria < 2000 mg/g or > /=2000 mg/g , within the higher proteinuria stratum ( > /=2000 mg/g ) , patients in the losartan group had a higher baseline mean proteinuria value . When the imbalance was adjusted , an increase in the magnitude and the significance of the risk reduction with losartan for each outcome was observed . No apparent interaction between treatment effect and baseline proteinuria was found , and there was no heterogeneity in the treatment response in patients with different baseline proteinuria levels . After proteinuria was adjusted as a continuous variable , greater treatment effects were observed in the RENAAL study . This effect was due solely to the imbalance in baseline proteinuria . Considering the importance of proteinuria as a risk factor , adjustment for baseline proteinuria as a continuous covariate should be prespecified in the design and analysis of clinical trials involving renal outcomes , even when patients are stratified on the basis of level of proteinuria BACKGROUND It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure . METHODS We r and omly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan ( 300 mg daily ) , amlodipine ( 10 mg daily ) , or  placebo .  The target blood pressure was 135/85 mm Hg or less in all groups . We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration , the development of end-stage renal disease , or death from any cause . We also compared them with regard to the time to a secondary , cardiovascular composite end point . RESULTS The mean duration of follow-up was 2.6 years . Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group ( P=0.02 ) and 23 percent lower than that in the amlodipine group ( P=0.006 ) . The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group ( P=0.003 ) and 37 percent lower in the irbesartan group than in the amlodipine group ( P<0.001 ) . Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups ( P=0.07 for both comparisons ) . These differences were not explained by differences in the blood pressures that were achieved . The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group ( P=0.008 ) and 21 percent more slowly than in the amlodipine group ( P=0.02 ) . There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point . CONCLUSIONS The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes . This protection is independent of the reduction in blood pressure it causes BACKGROUND Chronic allograft nephropathy ( CAN ) is the leading cause of late allograft failure , with only limited treatment options . Blockade of the renin-angiotensin system ( RAS ) decreases progression in diabetic and non-diabetic renal disease , but the effect on CAN is as yet unclear . Therefore , we have studied retrospectively the effect of RAS blockade on renal survival in patients with biopsy-proven CAN . METHODS The medical records of 72 patients with biopsy-proven CAN were evaluated with regard to time course of graft function , proteinuria , blood pressure , and antihypertensive and immunosuppressive treatment . Cox 's proportional hazards model was used for analysing renal graft survival after the index biopsy . RESULTS On univariate analysis , histological determinants influencing renal survival were the chronic interstitial and chronic tubular score , and clinical parameters were the serum creatinine level at the time of the biopsy , the relative change in serum creatinine level between 12 months post-transplantation and at the time of the biopsy , mean systolic and diastolic blood pressure after the biopsy , and RAS blockade by angiotensin-converting enzyme inhibitor or angiotensin receptor blocker . On multivariate analysis , graft outcome was influenced by the relative change in serum creatinine level between 12 months post-transplantation and the time of the index biopsy , the urinary protein excretion , the mean diastolic blood pressure after the index biopsy , and RAS blockade . Renal graft survival after treatment with RAS blockade was 6.3 ( 0.9 - 10.9 ) years as opposed to 1.8 ( 0.1 - 6.7 ) years in untreated patients ( P = 0.003 ) . CONCLUSION RAS blockade increases graft survival in CAN . In view of the limited treatment options for CAN , this finding is of importance and needs confirmation by a prospect i ve r and omized trial A report of a r and omized , controlled trial ( RCT ) should convey to the reader , in a transparent manner , why the study was undertaken and how it was conducted and analyzed . For example , a lack of adequately reported r and omization has been associated with bias in estimating the effectiveness of interventions ( 1 , 2 ) . To assess the strengths and limitations of an RCT , readers need and deserve to know the quality of its methods . Despite several decades of educational efforts , RCTs still are not being reported adequately ( 3 - 6 ) . For example , a review of 122 recently published RCTs that evaluated the effectiveness of selective serotonin-reuptake inhibitors as first-line management strategy for depression found that only 1 ( 0.8 % ) paper described r and omization adequately ( 5 ) . Inadequate reporting makes the interpretation of RCT results difficult if not impossible . Moreover , inadequate reporting borders on unethical practice when biased results receive false credibility . History of CONSORT In the mid-1990s , two independent initiatives to improve the quality of reports of RCTs led to the publication of the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement ( 7 ) , which was developed by an international group of clinical trialists , statisticians , epidemiologists , and biomedical editors . CONSORT has been supported by a growing number of medical and health care journals ( 8 - 11 ) and editorial groups , including the International Committee of Medical Journal Editors ( ICMJE , also known as the Vancouver Group ) ( 12 ) , the Council of Science Editors ( CSE ) , and the World Association of Medical Editors ( WAME ) . CONSORT is also published in Dutch , English , French , German , Japanese , and Spanish . It can be accessed on the Internet , along with other information about the CONSORT group ( 13 ) . The CONSORT statement comprises a checklist and flow diagram for reporting an RCT . For convenience , the checklist and diagram together are called simply CONSORT . They are primarily intended for use in writing , review ing , or evaluating reports of simple two-group , parallel RCTs . Preliminary data indicate that the use of CONSORT does indeed help to improve the quality of reports of RCTs ( 14 , 15 ) . In an evaluation ( 14 ) of 71 RCTs published in three journals in 1994 , allocation concealment was not clearly reported in 43 ( 61 % ) of the RCTs . Four years later , after these three journals required that authors reporting an RCT use CONSORT , the proportion of papers in which allocation concealment was not clearly reported had dropped to 39 % ( 30 of 77 ; mean difference , 22 % [ 95 % CI of the difference , 38 % to 6 % ] ) . The usefulness of CONSORT is enhanced by continuous monitoring of the biomedical literature ; this monitoring allows CONSORT to be modified depending on the merits of maintaining or dropping current items and including new items . For example , when Meinert ( 16 ) observed that the flow diagram did not provide important information about the number of participants who entered each phase of an RCT ( enrollment , treatment allocation , follow-up , and data analysis ) , the diagram could be modified to accommo date the information . The checklist is similarly flexible . This iterative process makes the CONSORT statement a continually evolving instrument . While participants in the CONSORT group and their degree of involvement vary over time , members meet regularly to review the need to refine CONSORT . At the 1999 meeting , the participants decided to revise the original statement . This report reflects changes determined by consensus of the CONSORT group , partly in response to emerging evidence on the importance of various elements of RCTs . Revision of the CONSORT Statement Thirteen members of the CONSORT group met in May 1999 with the primary objective of revising the original CONSORT checklist and flow diagram , as needed . The group discussed the merits of including each item in the light of current evidence . As in developing the original CONSORT statement , our intention was to keep only those items deemed fundamental to reporting st and ards for an RCT . Some items not considered essential may well be highly desirable and should still be included in an RCT report even though they are not included in CONSORT . Such items include approval of an institutional ethical review board , sources of funding for the trial , and a trial registry number ( as , for example , the International St and ard R and omized Controlled Trial Number [ IS RCT N ] used to register an RCT at its inception [ 17 ] ) . Shortly after the meeting , a revised version of the checklist was circulated to the group for additional comments and feedback . Revisions to the flow diagram were similarly made . All these changes were discussed when CONSORT participants met in May 2000 , and the revised statement was finalized shortly afterward . The revised CONSORT statement includes a 22-item checklist ( Table ) and a flow diagram ( Figure ) . Its primary aim is to help authors improve the quality of reports of simple two-group , parallel RCTs . However , the basic philosophy underlying the development of the statement can be applied to any design . In this regard , additional statements for other design s will be forthcoming from the group ( 13 ) . CONSORT can also be used by peer review ers and editors to identify reports with inadequate description of trials and those with potentially biased results ( 1 , 2 ) . Table . Checklist of Items To Include When Reporting a R and omized Trial Figure . Flow diagram of the progress through the phases of a r and omized trial ( enrollment , intervention allocation , follow-up , and data analysis ) . During the 1999 meeting , the group also discussed the benefits of developing an explanatory document to enhance the use and dissemination of CONSORT . The document is patterned on reporting of statistical aspects of clinical research ( 18 ) , which was developed to help facilitate the recommendations of the ICMJE 's Uniform Requirements for Manuscripts Su bmi tted to Biomedical Journals . Three members of the CONSORT group , with assistance from members on some checklist items , drafted an explanation and elaboration document . That document ( 19 ) was circulated to the group for additions and revisions and was last revised after review at the latest CONSORT group meeting . Changes to CONSORT 1 . In the revised checklist , a new column for Paper Section and Topic integrates information from the Subheading column that was contained in the original statement . 2 . The Was It Reported ? column has been integrated into a Reported on Page Number column , as requested by some journals . 3 . Each item of the checklist is now numbered , and the syntax and order have been revised to improve the flow of information . 4 . Title and Abstract are now combined in the first item . 5 . While the content of the revised checklist is similar to that of the original one , some items that previously were combined are now separate . For example , authors had been asked to describe primary and secondary outcome ( s ) measure(s ) and the minimum important difference(s ) , and indicate how the target sample size was projected . In the new version , issues pertaining to outcomes ( item 6 ) and sample size ( item 7 ) are separate , enabling authors to be more explicit about each . Moreover , some items request additional information . For example , for outcomes ( item 6 ) authors are asked to report any methods used to enhance the quality of measurements , such as multiple observations . 6 . The item asking for the unit of r and omization ( for example , cluster ) has been dropped because specific checklists have been developed for reporting cluster RCTs ( 20 ) and other design types ( 13 ) since publication of the original checklist . 7 . Whenever possible , new evidence is incorporated into the revised checklist . For example , authors are asked to be explicit about whether the analysis reported is by intention to treat ( item 16 ) . This request is based in part on the observations ( 21 ) that authors do not adequately describe and apply intention-to-treat analysis and that reports not providing this information are less likely to provide other relevant information , such as losses to follow-up ( 22 ) . 8 . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow-up , and 
    Output:
    
Proteinuria decreased significantly in group A patients only .
Lisinopril also significantly reduced radiolabeled aprotinin uptake and metabolism , plasma aldosterone , and ammonia excretion .
Patients with more than or equal to 30 % reduction in proteinuria had a significant association with rs699 polymorphism in the angiotensinogen gene .
The rate of decline of renal graft function in patients with chronic allograft nephropathy was not adversely affected by lisinopril therapy given for 1 year .
Lisinopril significantly reduced proteinuria , renal proximal tubular polypeptide catabolism , plasma aldosterone , and ammonia excretion suggesting relative preservation of graft function .
Treating metabolic acidosis allowed safe and prolonged use of angiotensinogen-converting enzyme inhibitors