title: Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease: a systematic review of the efficacy and safety data.
abstract: Blockade of the renin-angiotensin system with either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) was shown to decrease urinary protein excretion and slow the progression of both diabetic and nondiabetic proteinuric renal disease. The safety and efficacy of combined ACE-inhibitor and ARB therapy is not well established. We conducted a systematic review and meta-analysis of randomized trials evaluating the combination of an ACE inhibitor and an ARB in patients with chronic proteinuric renal disease. Twenty-one randomized controlled studies (n = 654 patients) were identified using MEDLINE, EMBASE, and Cochrane Central databases. Five trials had a parallel-group design and 16 trials used a crossover design. Combination therapy with an ACE inhibitor and an ARB resulted in a small, but significant, increase in serum potassium levels (weighted mean difference, 0.11 mEq/L [0.11 mmol/L]; 95% confidence interval [CI], 0.05 to 0.17) and a nonsignificant decrease in glomerular filtration rate (weighted mean difference, 1.4 mL/min [0.02 mL/s]; 95% CI, -2.6 to 0.2). Addition of an ARB resulted in a further decrease in proteinuria (weighted mean difference, 440 mg/d; 95% CI, 289 to 591) compared with an ACE inhibitor alone. This effect was observed in patients with diabetic (210 mg/d; 95% CI, 84 to 336) and nondiabetic (582 mg/d; 95% CI, 371 to 793) renal disease. In conclusion, the combination of ACE-inhibitor and ARB therapy in patients with chronic proteinuric renal disease is safe, without clinically meaningful changes in serum potassium levels or glomerular filtration rates. Combination therapy also was associated with a significant decrease in proteinuria, at least in the short term. Additional trials with longer follow-up are needed to determine whether the decrease in proteinuria will result in significant preservation of renal function.
authors.affiliation: Department of Medicine, Division of Nephrology, University of Ottawa, Ottawa, Ontario, Canada. mmackinnon2545@rogers.com
authors.forename: Martin
authors.initials: M
authors.lastname: MacKinnon
authors.forename: Sabin
authors.initials: S
authors.lastname: Shurraw
authors.forename: Ayub
authors.initials: A
authors.lastname: Akbari
authors.forename: Greg A
authors.initials: GA
authors.lastname: Knoll
authors.forename: James
authors.initials: J
authors.lastname: Jaffey
authors.forename: Heather D
authors.initials: HD
authors.lastname: Clark
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003928:Diabetic Nephropathies / Q000517:prevention & control; D004359:Drug Therapy, Combination; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D011507:Proteinuria / Q000150:complications; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors