***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: OBJECTIVE --To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy ( albuminuria greater than 300 mg/24h ) . DESIGN --Open r and omised controlled study of four years ' duration . SETTING --Outpatient diabetic clinic in tertiary referral centre . PATIENTS --44 normotensive ( mean blood pressure 127/78 ( SD 12/10 ) mm Hg ) insulin dependent diabetic patients with persistent microalbuminuria ( 30 - 300 mg/24h ) . INTERVENTIONS --The treatment group ( n = 21 ) was initially given captopril ( 25 mg/24 h ) . The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months . The remaining 23 patients were left untreated . MAIN OUTCOME MEASURES --Albuminuria , kidney function , development of diabetic nephropathy ( albuminuria greater than 300 mg/24 h ) , and arterial blood pressure . RESULTS -- Clinical and laboratory variables were comparable at baseline . Urinary excretion of albumin was gradually reduced from 82 ( 66 - 106 ) to 57 ( 39 - 85 ) mg/24 h ( geometric mean ( 95 % confidence interval ) ) in the captopril treated group , whereas an increase from 105(77 - 153 ) to 166 ( 83 - 323 ) mg/24 h occurred in the control group ( p less than 0.05 ) . Seven of the untreated patients progressed to diabetic nephropathy , whereas none of the captopril treated patients developed clinical overt diabetic nephropathy ( p less than 0.05 ) . Systemic blood pressure , glomerular filtration rate , haemoglobin A1c concentration , and urinary excretion of sodium and urea remained practically unchanged in the two groups . CONCLUSIONS --The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria Recent studies utilizing converting enzyme inhibitors ( CEI ) in diabetic rats document reductions in both renal hypertrophy and albuminuria . Four separate clinical studies in normotensive patients with diabetes demonstrate reduction of microalbuminuria with CEIs independent of blood pressure reduction . The present pilot study examines the results of reducing an elevated glomerular filtration rate on changes in renal size and microalbuminuria in normotensive , hyperfiltering insulin-dependent diabetic ( IDDM ) patients . Fifteen IDDM patients were r and omized to either placebo or the CEI , lisinopril . Dosage of lisinopril was titrated over 3 months to reduce glomerular filtration rate ( GFR ) to < or = 2.33 mL/sec . Evaluation at 18 months demonstrated the lisinopril group had a marked reduction in renal size ( 16.9 + /- 1.1 , baseline versus 12.8 + /- 0.9 cm , 18 months ; p < 0.05 ) and microalbuminuria ( 92 + /- 11 micrograms/min , baseline versus 23 + /- 26 micrograms/min , 18 months ; p < 0.05 ) . No change in renal size was noted in the placebo group ( 15.4 + /- 0.8 , baseline versus 14.9 + /- 0.7 cm , 18 months ; NS ) and albuminuria increased ( 118 + /- 15 micrograms/min , baseline versus 293 + /- 32 micrograms/min , 18 months ; p < 0.05 ) . Mean arterial pressure at 18 months was significantly lower in the lisinopril group compared to placebo ( 102 + /- 4 , placebo versus 87 + /- 6 mm Hg , CEI , p < 0.05 ) . This study supports previous animal studies that document reductions in both microalbuminuria and renal size by a CEI . The overall impact of these findings on preservation of renal function can not be assessed , however , in this short-term study STUDY OBJECTIVE --To assess the effectiveness of inhibition of angiotensin converting enzyme in preventing diabetic nephropathy . DESIGN --R and omised follow up study of normotensive diabetics with persistent microalbuminuria ( 30 - 300 mg/24 hours ) treated with enalapril or its matched placebo for one year . Double blind for first six months , single blind for last six months . SETTING --Diabetic clinic in tertiary referral centre . PATIENTS --Treatment group and placebo group each comprised 10 normotensive diabetics with persistent microalbuminuria . INTERVENTIONS --Treatment group was given enalapril 20 mg daily and controls matched placebo . Patients were given antihypertensive treatment after one year . END POINT -- Albumin excretion , arterial pressure , and renal function . MAIN RESULTS --In last three months of trial three of 10 patients taking placebo had diabetic nephropathy ( albumin excretion greater than 300 mg/24 hours ) . No patients taking enalapril developed nephropathy and five showed normal albumin excretion ( less than 30 mg/24 hours ) ( p = 0.005 , Mann-Whitney test ) . Mean arterial pressure was reduced by enalapril throughout study ( p less than 0.005 ) but increased linearly with placebo ( p less than 0.05 ) . Albumin excretion decreased linearly with enalapril but not placebo . An increase in albumin excretion with placebo was positively related to the increase in mean arterial pressure ( r = 0.709 , p less than 0.05 , Spearman 's rank test ) . With enalapril  total renal resistances and fractional albumin clearances improved progressively ( time effect , p = 0.0001 ) . CONCLUSION --Inhibition of angiotensin converting enzyme prevents development of nephropathy in normotensive diabetics with persistent microalbuminuria . This may be due to reduction in intraglomerular pressure and to prevention of increased systemic blood pressure . Future studies should compare long term effects of inhibitors of converting enzyme with other antihypertensive drugs The effect of early aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospect ively in ten insulin-dependent diabetics ( mean age 29 years ) . During the mean pretreatment period of 29 ( range 23 - 38 ) months the glomerular filtration rate ( GFR ) decreased significantly and the urinary albumin excretion rate and arterial blood pressure rose significantly . During the 39 month ( range 28 - 48 ) period of antihypertensive treatment with metoprolol , hydralazine , and frusemide ( furosemide ) or thiazide , arterial blood pressure fell from 144/97 mm Hg ( mean of all pretreatment values ) to 128/84 mm Hg ( mean of all post-treatment values ) , urinary albumin excretion from 977 micrograms/min to 433 micrograms/min , and GFR from 80 to 62 ml/min/1 . 73 m2 . The rate of decline in GFR decreased from 0.91 ml/min/month before treatment to 0.39 ml/min/month ( range 0.08 to 0.68 ml/min/month ) during treatment The beneficial effect of long-term treatment with an angiotensin-converting enzyme ( ACE ) inhibitor on urinary microalbumin excretion ( UAE ) and renal function was investigated in a 4 year , r and omized prospect i ve study in normotensive patients with non-insulin-dependent ( Type 2 ) diabetes mellitus . Sixty-two normotensive patients with Type 2 diabetes mellitus and microalbuminuria but normal renal function were r and omized to receive either enalapril 5 mg day-1 or no treatment . In the enalapril-treated patients , UAE was reduced from 115.4 + /- 80.1 to 95.6 + /- 61.7 mg 24 h-1 after 12 months ( p < 0.05 ) and to 75.3 + /- 44.8 mg 24 h-1 after 48 months ( p < 0.001 ) . In the untreated group , UAE increased slowly from 93.9 + /- 69.9 to 150.0 + /- 144.5 mg 24 h-1 after 48 months . No changes in creatinine clearance , blood pressure or HbA1C were seen in either group during the 4-year period . In normotensive Type 2 diabetic patients with early stage of diabetic microalbuminuria . This effect is long-lasting and probably independent of the antihypertensive action of the drug BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries . Duration of diabetes , blood pressure values , and metabolic status are the major determinants of the course of nephropathy , and microalbuminuria is the hallmark of its onset . Angiotensin-converting enzyme inhibitors offer important renoprotection to hypertensive and normotensive patients with insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus . Our study extends previous observations for duration and the effect of angiotensin-converting enzyme inhibition on advanced nephropathy . METHODS Double-blinded ( first phase ) and open ( second phase ) r and omized controlled study of 7 years . Ninety-four normotensive patients with non-insulin-dependent diabetes mellitus whose serum creatinine levels were lower than 123.76 mumol/L ( 1.4 mg/dL ) and who had microalbuminuria ( 30 to 300 mg/24 h ) were given enalapril maleate , 10 mg/d , or placebo , for 5 years . For 2 more years they were followed up openly and given the choice to receive enalapril or no treatment . RESULTS In the enalapril-treated patients , albuminuria remained stable for 7 years . An increase from ( mean + /- SD ) 123 + /- 58 to 310 + /- 167 mg/24 h occurred in the untreated group after 5 years , and a further increase to ( mean + /- SD ) 393 + /- 223 mg/24 h occurred after 7 years . Reciprocal creatinine was unchanged in treated patients for 7 years ; in the untreated patients , the mean decline was 13 % at 5 years and 16 % at 7 years . Treatment with enalapril result ed in an absolute risk reduction of 42 % for nephropathy to develop during 7 years ( 95 % confidence interval , 15 % to 69 % ; P < .001 , Student 's t test ) . Glycosylated hemoglobin and body mass index remained unchanged . CONCLUSIONS Angiotensin-converting enzyme inhibition offers long-term protection against the development of nephropathy in normotensive patients with noninsulin-dependent diabetes mellitus who have microalbuminuria , and it stabilizes renal function in previously untreated patients with impaired renal function . Discontinuation of treatment results in renewed progression of nephropathy OBJECTIVE --To compare the effects of sodium depletion and of angiotensin I converting enzyme inhibition on microalbuminuria in insulin dependent diabetes . DESIGN --R and omised , double blind , double dummy parallel study of normotensive diabetic patients with persistent microalbuminuria ( 30 - 300 mg/24 h ) treated with enalapril or hydrochlorothiazide for one year after a three month , single blind placebo period . SETTING --Diabetic clinic in a tertiary referral centre . PATIENTS --10 diabetic patients with low microalbuminuria ( 30 - 99 mg/24 h ) and 11 with high microalbuminuria ( 100 - 300 mg/24 h ) . INTERVENTIONS --11 subjects ( six with low microalbuminuria , five with high microalbuminuria ) were given enalapril 20 mg plus placebo hydrochlorothiazide once daily and 10 ( four with low microalbuminuria , six with high microalbuminuria ) hydrochlorothiazide 25 mg plus placebo enalapril once daily . MAIN OUTCOME MEASURES --Monthly assessment of urinary albumin excretion and mean arterial pressure ; plasma active renin and aldosterone concentrations and renal function studies at 0 , 6 , and 12 months . RESULTS --Median urinary albumin excretion decreased from 59 ( range 37 - 260 ) to 38 ( 14 - 146 ) mg/24 h with enalapril and from 111 ( 33 - 282 ) to 109 ( 33 - 262 ) mg/24 h with hydrochlorothiazide ( analysis of variance , p = 0.0436 ) . During the last three months 
    Output:
    
Treatment provided a significant reduction in albumin excretion rate in both insulin dependent diabetes mellitus and non insulin dependent diabetes mellitus .
Treatment with either captopril , enalapril or lisinopril reduced albumin excretion rate in comparison with control patients .
A significantly greater lowering of blood pressure was experienced by initially normotensive patients in the angiotensin converting enzyme inhibitor than in the placebo group .
Average glycosylated haemoglobin fell a little in the treated patients and rose in the controls , the difference being just significant .
The difference in changes in glomerular filtration rate did not reach statistical significance .
REVIEW ER 'S CONCLUSIONS Inhibition of angiotensin converting enzyme can arrest or reduce the albumin excretion rate in microalbuminuric normotensive diabetics , as well as reduce or prevent an increase in blood pressure .
But , given the drop in blood pressure in patients on angiotensin converting enzyme inhibitors , it is not certain that the reduction of albumin excretion rate is due to a separate renal effect .
A direct link with postponement of end-stage renal failure has not been demonstrated .
There appear to be no substantial side effects