***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: BACKGROUND Renin-angiotensin system inhibitors have renoprotective effects in patients with chronic kidney disease , but most patients treated with these drugs have residual urinary albumin excretion . Some small clinical studies show that mineralocorticoid receptor blockade reduces albuminuria . Our study aim ed to examine the beneficial effects of addition of a selective aldosterone antagonist , eplerenone , to renin-angiotensin system inhibitors in hypertensive patients with non-diabetic chronic kidney disease . METHODS In this double-blind , r and omised , placebo-controlled trial , we enrolled hypertensive patients , aged 20–79 years , with albuminuria ( urinary albumin-to-creatinine ratio [ UACR ] in the first morning void urine of 30–599 mg/g ) , an estimated glomerular filtration rate of 50 mL/min per 1·73 m2 or more , and who had received an angiotensin-converting enzyme inhibitor , an angiotensin receptor blocker , or both , for at least 8 weeks . Participants were from 59 clinics and hospitals in Japan . Eligible patients were r and omly assigned ( 1:1 ) , stratified by baseline characteristics , to either low-dose eplerenone ( 50 mg/day ) or placebo , with continuation of st and ard antihypertensive treatment to attain therapeutic goals ( < 130/80 mm Hg ) for 52 weeks . We assessed efficacy in all patients who received allocated treatment , provided a baseline and post-treatment urine sample , and remained in follow-up . We assessed safety in all patients who received allocated treatment . The primary efficacy measure was percent change in UACR in the first morning void urine at week 52 from baseline . The trial is registered at the clinical trials registry of University Hospital Medical Information Network ( UMIN ) , trial identification number UMIN000001803 . FINDINGS Between April 1 , 2009 , and March 31 , 2012 , we r and omly allocated 170 patients to the eplerenone group and 166 patients to the  placebo group . In the primary efficacy analysis , mean percent change in UACR from baseline was −17·3 % ( 95 % CI −33·65 to −0·94 ) for 158 patients in the eplerenone group compared with 10·3 % ( −6·75 to 22·3 ) for 146 patients in the placebo group ( absolute difference −27·6 % [ –51·15 to −3·96 ] ; p=0·0222 ) . In the safety analyses , 53 ( 31 % ) of 169 patients in the eplerenone  group had adverse events ( five serious ) , as did 49 ( 30 % ) of 163 in the placebo group ( seven serious ) . Although mean serum potassium concentration was higher in the eplerenone group than the placebo group , severe hyperkalaemia ( > 5·5 mmol/L ) was not recorded in either group . INTERPRETATION Addition of low-dose eplerenone to renin-angiotensin system inhibitors might have renoprotective effects through reduction of albuminuria in hypertensive patients with non-diabetic chronic kidney disease , without serious safety concerns . FUNDING Pfizer BACKGROUND Agents inhibiting the renin-angiotensin-aldosterone ( RAAS ) system have an important role in slowing the progression of chronic kidney disease . We evaluated the hypothesis that the addition of an aldosterone receptor antagonist to an angiotensin-converting enzyme ( ACE ) inhibitor and angiotensin II type 1 ( AT-1 ) receptor blocker ( ARB ) ( triple RAAS blockade ) may provide an additional benefit compared with an ACE inhibitor and ARB ( double RAAS blockade ) . DESIGN R and omized open controlled crossover study . SETTING & PARTICIPANTS 18 whites ( 7 women , 11 men ) from the Outpatient Department of Nephrology with chronic nondiabetic proteinuric kidney diseases , mean age 42.4 + /- 1.9 years ( SEM ) . INTERVENTIONS In the 8-week run-in period , all participants received the ACE inhibitor cilazapril ( 5 mg ) , the ARB telmisartan ( 80 mg ) , and the diuretic hydrochlorothiazide ( 12.5 mg ) as double RAAS blockade to achieve the target blood pressure of less than 130/80 mm Hg . Participants were then r and omly assigned to 2 treatment sequences , either the addition of spironolactone ( 25 mg ) ( triple RAAS blockade ) through 8 weeks followed by double RAAS blockade through 8 weeks ( sequence 1 ) or double RAAS blockade followed by triple RAAS blockade ( sequence 2 ) . MAIN OUTCOME MEASURES 24-hour urine protein excretion ( primary end point ) and markers of tubular injury and fibrosis ( secondary end points ) . Analysis was performed using analysis of variance for repeated measurements . RESULTS At baseline , mean serum creatinine level was 1.16 + /- 0.09 mg/dL ( 103 + /- 8 micromol/L ) , estimated glomerular filtration rate was 107.8 mL/min ( 95 % confidence interval , 93 to 140.9 [ 1.8 mL/s ; 95 % confidence interval , 1.55 to 2.35 ; Cockcroft-Gault formula ) , and 24-hour mean proteinuria was 0.97 + /- 0.18 g. Mean urine protein excretion was 0.7 g/24 h ( 95 % confidence interval , 0.48 to 0.92 ) less after triple RAAS blockade than after double RAAS blockade ( P = 0.01 ) , without change in blood pressure . Urine excretion of N-acetyl-beta-d-glucosaminidase ( P = 0.02 ) and amino-terminal propeptide of type III procollagen ( P = 0.05 ) also significantly decreased . Potassium levels increased significantly after triple therapy ( P = 0.02 ) . However , no patient was withdrawn because of adverse effects . LIMITATIONS Absence of blinding , small sample size , short treatment period , absence of histological assessment . CONCLUSIONS Administration of an aldosterone receptor antagonist in addition to double RAAS blockade with an ACE inhibitor and ARB may slow the progression of chronic kidney disease . Additional studies are necessary to confirm this result Background Reduction of proteinuria and blood pressure ( BP ) with blockers of the renin-angiotensin system ( RAS ) impairs the progression of chronic kidney disease ( CKD ) . The aldosterone antagonist spironolactone has an antiproteinuric effect , but its use is limited by side effects . The present study evaluated the short-term antiproteinuric effect and safety of the selective aldosterone antagonist eplerenone in non-diabetic CKD . Study Design Open r and omized cross-over trial . Setting and Participants Forty patients with non-diabetic CKD and urinary albumin excretion greater than 300 mg/24 hours . Intervention Eight weeks of once-daily administration of add-on 25–50 mg eplerenone to stable st and ard antihypertensive treatment including RAS-blockade . Outcomes & Measurements 24 hour urinary albumin excretion , BP , p-potassium , and creatinine clearance . Results The mean urinary albumin excretion was 22 % [ CI : 14,28 ] , P<0.001 , lower during treatment with eplerenone  . Mean systolic BP was 4 mmHg [ CI : 2,6 ] , P = 0.002 , diastolic BP was 2 mmHg [ CI : 0,4 ] , P = 0.02 , creatinine clearance was 5 % [ CI : 2,8 ] , P = 0.005 , lower during eplerenone treatment . After correction for BP and creatinine clearance differences between the study periods , the mean urinary albumin excretion was 14 % [ CI : 4,24 ] , P = 0.008 lower during treatment . Mean p-potassium was 0.1 mEq/L [ CI : 0.1,0.2 ] higher during eplerenone treatment , P<0.001 . Eplerenone was thus well tolerated and no patients were withdrawn due to hyperkalaemia . Limitations Open label , no wash-out period and a moderate sample size . Conclusions In non-diabetic CKD patients , the addition of eplerenone to st and ard antihypertensive treatment including RAS-blockade caused a moderate BP independent fall in albuminuria , a minor fall in creatinine clearance and a 0.1 mEq/L increase in p-potassium . Trial Registration Clinical trials.gov Experimental evidence suggests that aldosterone contributes to progressive kidney disease .  Angiotensin-converting enzyme inhibitors and angiotensin type 1 receptor antagonists suppress the renin-angiotensin system but they do not effectively reduce plasma aldosterone . Hence , administration of aldosterone receptor antagonists may provide additional renal protection . In the present prospect i ve r and omized open-label study , we evaluated the effects of spironolactone ( 25 mg/day for 1 year ) on proteinuria and estimated glomerular filtration rate in 83 patients with chronic kidney disease already treated with angiotensin-converting enzyme inhibitors and /or angiotensin type 1 receptor antagonists . Eighty-two patients were treated with angiotensin-converting enzyme inhibitors and /or angiotensin type 1 receptor antagonists alone and served as controls . After 1 year of therapy , proteinuria decreased from 2.1+/-0.08 to 0.89+/-0.06 g/g creatinine ( P<0.001 ) in patients treated with spironolactone , but it did not change in control patients . Baseline aldosterone levels were significantly correlated with proteinuria ( r=0.76 , P<0.0001 ) , and predicted the degree of reduction in proteinuria with spironolactone ( r=0.42 , P<0.0002 ) . Baseline estimated glomerular filtration rate was similar in patients treated with spironolactone and controls ( 62.4+/-2.4 and 62.2+/-2.1 ml/min/1.73 m(2 ) , respectively ) . After 1 month of therapy with spironolactone , estimated glomerular filtration rate decreased more in patients treated with spironolactone than in controls . However , by the end of 1 year the monthly rate of decrease in estimated glomerular filtration rate from baseline was lower in patients treated with spironolactone than in controls ( 0.323+/-0.044 vs 0.474+/-0.037 ml/min/1.73 m(2 ) , P<0.01 ) . Spironolactone caused a significant rise in serum potassium levels ( from 4.2+/-0.04 at baseline to 5.0+/-0.05 mEq/l after 12 months of treatment , P<0.001 ) . In conclusion , this study has shown that spironolactone may reduce proteinuria and retard renal progression in chronic kidney disease patients BACKGROUND Aldosterone has been suggested to play a role in the initiation and progression of diabetic nephropathy . Currently recommended treatment with angiotensin-converting enzyme ( ACE ) inhibitors or angiotensin II receptor blockers [ renin-angiotensin system ( RAS ) blockade ] does not suppress circulating aldosterone sufficiently . We therefore aim ed to evaluate the short-term effect of aldosterone antagonism with spironolactone on albuminuria and blood pressure in diabetic nephropathy . METHODS Twenty Caucasian type 1 diabetic patients with persistent macroalbuminuria despite antihypertensive treatment , including RAS blockade , completed this double-masked , r and omized cross-over trial . Patients were treated in r and om order with spironolactone 25 mg once daily and matched placebo for two months , respectively , on top of usual antihypertensive treatment . After each treatment period albuminuria , 24-hour blood pressure , and glomerular filtration rate ( GFR ) were determined . RESULTS Spironolactone on top of usual antihypertensive treatment induced a 30 % ( 95 % CI 17 to 41 ) reduction in albuminuria from [ geometric mean ( 95 % CI ) ] 831 ( 624 to 1106 ) mg/24-hour on placebo treatment ( P < 0.001 ) , and a reduction in fractional albumin clearance of 35 % ( 20 to 46 , P < 0.001 ) . Twenty-four-hour blood pressure showed an insignificant reduction of [ mean reduction ( 95 % CI ) ] 8 ( -1 to 17)/3 ( -0.2 to 7 ) mm Hg ( P < 0.10 ) . There was an insignificant reversible reduction in GFR during treatment with spironolactone . On spironolactone treatment , one patient was excluded due to  hyperkalemia  ( plasma potassium 5.7 mmol/L ) and one due to orthostatic dizziness . Otherwise treatment was well tolerated . CONCLUSION Our results suggest that spironolactone treatment 
    Output:
    
Conclusions Mineralocorticoid receptor antagonism reduces blood pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit