title: Sequential RAAS blockade: is it worth the risk?
abstract: Soon after the emergence of the renin-angiotensin-aldosterone system (RAAS) blocking treatment as the cornerstone of renoprotective treatment in the prevention and treatment of diabetic and nondiabetic CKD, it was investigated if a higher degree of achievable RAAS blockade by combining more than one compound is feasible and advantageous. Regardless of the benefits from using monotherapy for diabetic kidney disease, there is still much improvement to wish for in terms of kidney prognosis in these populations. A great deal of research has gone into evaluating combinations of the RAAS blocking treatments in different populations and with different drugs and doses. Studies have mostly been short-term and use surrogate endpoints such as albuminuria. Side effects have been well known and expected in terms of increasing potassium levels and hypotension, but to an acceptable extent. With recent disappointing results from major hard endpoint trials using dual RAAS blockade the concept is now under scrutiny. In this review we will discuss the pros and cons of dual RAAS blockade, with facts and findings from smaller studies, endpoint trials, and meta-analyses.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark; and Steno Diabetes Center, Gentofte, Denmark; Faculty of Health Sciences, Aarhus University, Aarhus, Denmark and NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. Electronic address: Frip@steno.dk.
authors.forename: Frederik
authors.initials: F
authors.lastname: Persson
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark; and Steno Diabetes Center, Gentofte, Denmark; Faculty of Health Sciences, Aarhus University, Aarhus, Denmark and NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000577:Amides / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005650:Fumarates / Q000627:therapeutic use; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000517:prevention & control*; D012084:Renin-Angiotensin System; D018570:Risk Assessment; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005650:Fumarates; D000451:Mineralocorticoid Receptor Antagonists; D000092502:Renin Inhibitors; C446481:aliskiren
keywords: Chronic kidney disease; Dual blockade; Hyperkalemia; RAAS; Renin inhibition