***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: Abstract To compare the efficacy of spironolactone and trichlormethiazide , as add‐on therapy to renin – angiotensin system ( RAS ) blockade , for reduction of albuminuria in diabetic patients with chronic kidney disease ( CKD ) , we conducted this r and omized , open‐labeled , parallel‐group , active‐controlled , per‐ protocol ‐ design study . Type 2 diabetic patients receiving an angiotensin‐converting enzyme inhibitor or angiotensin II receptor blocker , with persistent albuminuria ( ≥100 mg/g creatinine ) were r and omly assigned to either spironolactone ( 25 mg/day ) or trichlormethiazide ( 2 mg/day ) . The primary outcome was the change in albuminuria at 24 weeks of treatment . In patients who completed 24 weeks of treatment with spironolactone ( n = 18 ) and trichlormethiazide ( n = 15 ) , albuminuria decreased significantly by −57.6 ± 21.3 % ( SD ) ( P < 0.001 ) and −48.4 ± 27.1 % ( P < 0.001 ) , respectively . There was no significant difference in the change in albuminuria between groups ( P = 0.270 ) . This pilot study suggests add‐on therapy with spironolactone or trichlormethiazide to RAS blockade may be comparably beneficial to reducing albuminuria in type 2 diabetic patients . This trial was registered with UMIN‐CTR ( no. UMIN000008914 ) 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 The  efficacy and tolerability of eplerenone , a selective aldosterone blocker , was assessed when added to existing antihypertensive therapy with an ACE inhibitor or an angiotensin II receptor blocker ( ARB ) . Hypertensive patients ( n=341 ) whose blood pressure ( BP ) was not controlled despite ACE inhibitor or ARB  were r and omized ( double-blind ) to receive 50 mg eplerenone ( increasing to 100 mg if required ) once daily or placebo for 8 weeks . Diastolic and systolic BP and adverse events were recorded . By study end ( week 8) , mean seated diastolic BP was significantly reduced from week 0 among patients receiving eplerenone/ARB ( −12.7±0.81 mm Hg ) compared with those receiving placebo/ARB ( −9.3±0.83 mm Hg ) . The change in mean seated diastolic BP was −9.9±0.88 mm Hg in eplerenone/ACE inhibitor patients and −8.0±0.86 mm Hg in placebo/ACE inhibitor patients ( P = NS ) . Systolic BP levels were also significantly lower at week 8 for eplerenone/ACE inhibitor ( −13.4±1.35 mm Hg ) and eplerenone/ARB ( −16.0±1.37 mm Hg ) patients , respectively , compared with placebo/ACE inhibitor ( −7.5±1.31 mm Hg ) and placebo/ARB patients ( −9.2±1.41 mm Hg ) . Adverse events were generally nonsevere and not significantly different between eplerenone and placebo . This study demonstrated that in patients whose BP was not controlled with an ACE inhibitor or ARB , the addition of eplerenone over an 8-week period significantly lowered systolic BP in both groups and diastolic BP in ARB patients . Selective aldosterone blockade with eplerenone , therefore , may be useful add-on therapy in hypertensive patients inadequately controlled on ACE inhibitor or ARB alone Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication . We evaluated the effect among 1411 participants in the Anglo-Sc and inavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm who received spironolactone mainly as a fourth-line antihypertensive agent for uncontrolled blood pressure and who had valid BP measurements before and during spironolactone treatment . Among those who received spironolactone , the mean age was 63 years ( SD : ±8 years ) , 77 % were men , and 40 % had diabetes .  Spironolactone was initiated a median of 3.2 years ( interquartile range : 2.0 to 4.4 years ) after r and omization and added to a mean of 2.9 ( SD : ±0.9 ) other antihypertensive drugs . The median duration of spironolactone  treatment was 1.3 years ( interquartile range : 0.6 to 2.6 years ) . The median dose of spironolactone was 25 mg ( interquartile range : 25 to 50 mg ) at both the start and end of the observation period . During spironolactone therapy , mean blood pressure fell from 156.9/85.3 mm Hg ( SD : ±18.0/11.5 mm Hg ) by 21.9/9.5 mm Hg ( 95 % CI : 20.8 to 23.0/9.0 to 10.1 mm Hg ; P<0.001 ) ; the BP reduction was largely unaffected by age , sex , smoking , and diabetic status . Spironolactone was generally well tolerated ; 6 % of participants discontinued the drug because of adverse effects . The most frequent adverse events were gynecomastia or breast discomfort and biochemical abnormalities ( principally hyperkaliemia ) , which were recorded as adverse events in 6 % and 2 % of participants , respectively . In conclusion , spironolactone  effectively lowers blood pressure in patients with hypertension uncontrolled by a mean of ≈3 other drugs . Although nonr and omized and not placebo controlled , these data support the use of spironolactone in uncontrolled hypertension BACKGROUND Addition of spironolactone ( SPR ) to angiotensin-converting enzyme ( ACE ) inhibitors or angiotensin II receptor blockers ( ARBs ) might provide antiproteinuric effects beyond what is gained by either medication alone . This study was design ed to assess the long-term efficacy of SPR/ARB combination in comparison with the st and ard ACE/ARB regimen in diabetic nephropathy . METHODS In an open-label , parallel-group , single-center , r and omized clinical trial ( NCT01667614 ) , 136 patients with diabetes and proteinuria , already treated with enalapril and losartan , were included . In 74 patients , ACE inhibitors  were discontinued . After a wash-out period of 2 weeks , 25 mg SPR daily was initiated . The remainder of the patients ( n = 62 ) received ACE inhibitors and ARBs as before . Patients were followed every 3 months for 18 months . During each visit , systolic and diastolic blood pressure ( BP ) , urinary albumin excretion ( UAE ) , serum creatinine , estimated glomerular filtration rate ( eGFR ) and serum potassium concentrations were determined . RESULTS After 18 months , three patients in the SPR/ARB group developed asymptomatic hyperkalemia .  SPR/ARB significantly reduced both systolic and diastolic BP ( P < 0.001 and 0.001 , respectively ) . SPR/ARB  decreased UAE by 46 , 72 and 59 % after 3 , 12 and 18 months , respectively . Compared with the continuation regimen , SPR/ARB was superior in UAE reduction ( P = 0.017 after 18 months ) , independent of BP change . In both groups , eGFR declined significantly over the trial course and the decline rate did not differ significantly between the two groups . CONCLUSIONS Addition of SPR to ARB provides added benefits with respect to BP control and proteinuria diminution . These antiproteinuric effects are not accompanied by prevention of eGFR loss compared with conventional therapy with ACE/ARB Previous studies have shown that the selective aldosterone blocker eplerenone , in doses of up to 200 mg/d , reduces albuminuria in patients with type 2 diabetes . This study was conducted to ascertain whether lower doses of eplerenone ( 50 or 100 mg/d ) co-administered with the angiotensin-converting enzyme ( ACE ) inhibitor enalapril would produce a similar antialbuminuric effect while obviating the hyperkalemia observed previously . After open-label run-in with enalapril 20 mg/d , patients with diabetes and a urinary albumin : creatinine ratio ( UACR ) > or = 50 mg/g were r and omly assigned to receive enalapril plus one of three double-blind daily treatments for 12 wk : placebo , eplerenone 50 mg ( EPL50 ) , or eplerenone 100 mg ( EPL100 ) . After week 4 , amlodipine 2.5 to 10 mg/d was allowed for BP control ( systolic/diastolic BP < or = 130/80 mmHg ) . The primary study end points were the percentage change from baseline at week 12 in UACR and the incidence of hyperkalemia . Secondary end points included percentage changes from baseline in UACR at weeks 4 and 8 and changes from baseline in systolic and diastolic BP . Treatment with EPL50 or EPL100 but not placebo significantly reduced albuminuria from baseline . By week 12 , UACR was reduced by 7.4 % in the placebo group , by 41.0 % in the EPL50 group , and by 48.4 % in the EPL100 group ( both eplerenone groups , P < 0.001 versus placebo ) . The incidences of sustained and severe hyperkalemia were not significantly different in any of the three treatment arms and did not differ on the basis of quartile of estimated GFR ( all NS ) . For the secondary end points , both eplerenone treatment groups significantly reduced albuminuria from baseline as early as week 4 ( P < 0.001 ) , whereas placebo treatment ( including enalapril ) did not result in any significant decreases in UACR . Systolic BP decreased significantly 
    Output:
    
MRA further reduced SBP and DBP in patients with hypertension and DM already taking RAS inhibitors .