title: Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers.
abstract: Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis of the RENAAL and IDNT trials to test this in patients with type 2 diabetic nephropathy randomized to ARB or non-renin-angiotensin-aldosterone system (non-RAASi)-based antihypertensive therapy. Treatment effects on renal and cardiovascular outcomes were compared in subgroups based on dietary sodium intake during treatment, measured as the 24-h urinary sodium/creatinine ratio of 1177 patients with available 24-h urinary sodium measurements. ARB compared to non-RAASi-based therapy produced the greatest long-term effects on renal and cardiovascular events in the lowest tertile of sodium intake. Compared to non-RAASi, the trend in risk for renal events was significantly reduced by 43%, not changed, or increased by 37% for each tertile of increased sodium intake, respectively. The trend for cardiovascular events was significantly reduced by 37%, increased by 2% and 25%, respectively. Thus, treatment effects of ARB compared with non-RAASi-based therapy on renal and cardiovascular outcomes were greater in patients with type 2 diabetic nephropathy with lower than higher dietary sodium intake. This underscores the avoidance of excessive sodium intake, particularly in type 2 diabetic patients receiving ARB therapy.
authors.affiliation: Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. H.J.Lambers.Heerspink@med.umcg.nl
authors.forename: Hiddo J
authors.initials: HJ
authors.lastname: Lambers Heerspink
authors.forename: Frank A
authors.initials: FA
authors.lastname: Holtkamp
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Gerjan J
authors.initials: GJ
authors.lastname: Navis
authors.forename: Julia B
authors.initials: JB
authors.lastname: Lewis
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.forename: Pieter A
authors.initials: PA
authors.lastname: de Graeff
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000188:drug therapy; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy* / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000178:diet therapy* / Q000188:drug therapy* / Q000503:physiopathology; D004039:Diet, Sodium-Restricted; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects; D012964:Sodium / Q000652:urine
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D012964:Sodium; D003404:Creatinine