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.