title: Sodium intake, ACE inhibition, and progression to ESRD.
abstract: High sodium intake limits the antihypertensive and antiproteinuric effects of angiotensin-converting enzyme (ACE) inhibitors in patients with CKD; however, whether dietary sodium also associates with progression to ESRD is unknown. We conducted a post hoc analysis of the first and second Ramipril Efficacy in Nephropathy trials to evaluate the association of sodium intake with proteinuria and progression to ESRD among 500 CKD patients without diabetes who were treated with ramipril (5 mg/d) and monitored with serial 24-hour urinary sodium and creatinine measurements. Urinary sodium/creatinine excretion defined low (<100 mEq/g), medium (100 to <200 mEq/g), and high (≥200 mEq/g) sodium intake. During a follow-up of >4.25 years, 92 individuals (18.4%) developed ESRD. Among those with low, medium, and high sodium intakes, the incidence of ESRD was 6.1 (95% confidence interval [95% CI], 3.8-9.7), 7.9 (95% CI, 6.1-10.2), and 18.2 (95% CI, 11.3-29.3) per 100 patient-years, respectively (P<0.001). Patients with high dietary sodium exhibited a blunted antiproteinuric effect of ACE inhibition despite similar BP among groups. Each 100-mEq/g increase in urinary sodium/creatinine excretion associated with a 1.61-fold (95% CI, 1.15-2.24) higher risk for ESRD; adjusting for baseline proteinuria attenuated this association to 1.38-fold (95% CI, 0.95-2.00). This association was independent from BP but was lost after adjusting for changes in proteinuria. In summary, among patients with CKD but without diabetes, high dietary salt (>14 g daily) seems to blunt the antiproteinuric effect of ACE inhibitor therapy and increase the risk for ESRD, independent of BP control.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano, 87 - 24126 Bergamo, Italy.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vegter
authors.forename: Annalisa
authors.initials: A
authors.lastname: Perna
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: Postma
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology*; D017257:Ramipril / Q000627:therapeutic use*; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000009:adverse effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D012982:Sodium, Dietary; D012964:Sodium; D017257:Ramipril