BACKGROUND: Although dual blockade of the renin-angiotensin-aldosterone system (RAAS) has gained popularity for the treatment of kidney disease, its benefits and potential risks have not been fully elucidated. We conducted a meta-analysis of all randomized controlled trials comparing the efficacy and safety of combined vs. single RAAS blockade therapy in chronic kidney disease (CKD). METHODS: We performed a literature search using MEDLINE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, scientific abstracts from meetings, and bibliographies of retrieved articles. We used random-effects models to compute net changes and rate differences in variables. RESULTS: Fifty-nine (25 crossover and 34 parallel-arm) randomized controlled trials (RCTs) comparing the efficacy and safety of combined vs. single RAAS blockade therapy in CKD were identified (4,975 patients). Combined RAAS blockade therapy was associated with a significant net decrease in glomerular filtration rate (GFR) (-1.8ml/min or ml/min/1.73 m(2); P = 0.005), albuminuria (-90mg/g of creatinine; P = 0.001 or -32mg/day; P = 0.03), and proteinuria (-291mg/g; P = 0.003 or -363mg/day; P < 0.001). Combined RAAS blockade therapy was associated with a 9.4% higher rate of regression to normoalbuminuria and a 5% higher rate of achieving the blood pressure (BP) goal (as defined in individual trials). However, combined RAAS blockade therapy was associated with a significant net increase in serum potassium level, a 3.4% higher rate of hyperkalemia, and a 4.6% higher rate of hypotension. There was no effect on doubling of the serum creatinine level, hospitalization, or mortality. CONCLUSIONS: Although combined RAAS blockade therapy in CKD is associated with a decrease in albuminuria and proteinuria, it is associated with a decrease in GFR and a higher incidence of hyperkalemia and hypotension relative to monotherapy. The potential long-term kidney benefits of combined RAAS blockade therapy require further study.
BACKGROUND: Although dual blockade of the renin-angiotensin-aldosterone system (RAAS) has gained popularity for the treatment of kidney disease, its benefits and potential risks have not been fully elucidated. We conducted a meta-analysis of all randomized controlled trials comparing the efficacy and safety of combined vs. single RAAS blockade therapy in chronic kidney disease (CKD). METHODS: We performed a literature search using MEDLINE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, scientific abstracts from meetings, and bibliographies of retrieved articles. We used random-effects models to compute net changes and rate differences in variables. RESULTS: Fifty-nine (25 crossover and 34 parallel-arm) randomized controlled trials (RCTs) comparing the efficacy and safety of combined vs. single RAAS blockade therapy in CKD were identified (4,975 patients). Combined RAAS blockade therapy was associated with a significant net decrease in glomerular filtration rate (GFR) (-1.8ml/min or ml/min/1.73 m(2); P = 0.005), albuminuria (-90mg/g of creatinine; P = 0.001 or -32mg/day; P = 0.03), and proteinuria (-291mg/g; P = 0.003 or -363mg/day; P < 0.001). Combined RAAS blockade therapy was associated with a 9.4% higher rate of regression to normoalbuminuria and a 5% higher rate of achieving the blood pressure (BP) goal (as defined in individual trials). However, combined RAAS blockade therapy was associated with a significant net increase in serum potassium level, a 3.4% higher rate of hyperkalemia, and a 4.6% higher rate of hypotension. There was no effect on doubling of the serum creatinine level, hospitalization, or mortality. CONCLUSIONS: Although combined RAAS blockade therapy in CKD is associated with a decrease in albuminuria and proteinuria, it is associated with a decrease in GFR and a higher incidence of hyperkalemia and hypotension relative to monotherapy. The potential long-term kidney benefits of combined RAAS blockade therapy require further study.
Authors: G L Bakris; L Ruilope; F Locatelli; A Ptaszynska; B Pieske; J de Champlain; M A Weber; I Raz Journal: Kidney Int Date: 2007-08-01 Impact factor: 10.612
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Authors: Vicente E Torres; Kaleab Z Abebe; Arlene B Chapman; Robert W Schrier; William E Braun; Theodore I Steinman; Franz T Winklhofer; Godela Brosnahan; Peter G Czarnecki; Marie C Hogan; Dana C Miskulin; Frederic F Rahbari-Oskoui; Jared J Grantham; Peter C Harris; Michael F Flessner; Charity G Moore; Ronald D Perrone Journal: N Engl J Med Date: 2014-11-15 Impact factor: 91.245
Authors: Raquel Esteras; Maria Vanessa Perez-Gomez; Laura Rodriguez-Osorio; Alberto Ortiz; Beatriz Fernandez-Fernandez Journal: Ther Adv Drug Saf Date: 2015-08