Urinary sodium excretion and kidney failure in nondiabetic chronic kidney disease

Abstract

Current guidelines recommend under 2 g/day sodium intake in chronic kidney disease, but there are a few studies relating sodium intake to long-term outcomes. Here we evaluated the association of mean baseline 24-h urinary sodium excretion with kidney failure and a composite outcome of kidney failure or all-cause mortality using Cox regression in 840 participants enrolled in the Modification of Diet in Renal Disease Study. Mean 24-h urinary sodium excretion was 3.46 g/day. Kidney failure developed in 617 participants, and the composite outcome was reached in 723. In the primary analyses, there was no association between 24-h urine sodium and kidney failure (HR 0.99 (95% CI 0.91-1.08)) nor on the composite outcome (HR 1.01 (95% CI 0.93-1.09)), each per 1 g/day higher urine sodium. In exploratory analyses, there was a significant interaction of baseline proteinuria and sodium excretion with kidney failure. Using a two-slope model, when urine sodium was under 3 g/day, higher urine sodium was associated with increased risk of kidney failure in those with baseline proteinuria under 1 g/day and with lower risk of kidney failure in those with baseline proteinuria of ⩾ 1 g/day. There was no association between urine sodium and kidney failure when urine sodium was ⩾ 3 g/day. Results were consistent using first baseline and time-dependent urinary sodium excretion. Thus, we noted no association of urine sodium with kidney failure. Results of the exploratory analyses need to be verified in additional studies and the mechanism explored.

Figure 1. Unadjusted and adjusted restricted cubic splines for mean baseline 24-h urinary sodium excretion and kidney failure in the entire cohort

Splines were plotted using 4 default knots. p-value for nonlinearity of urine sodium were 0.251 in unadjusted model and 0.191 in adjusted model. Dashed lines indicate 95% CIs, and rugs at the bottom show location of each value for 24-h urine sodium. Splines were adjusted for age, sex, race, cause of kidney disease, measure GFR, log urine protein, BMI, SBP, LDL cholesterol, HDL cholesterol, smoking, diabetes, history of CVD, ACE inhibitor use, diuretic use, MDRD study A or B, and randomization to blood pressure and dietary protein target.

Figure 2. Forest plot of mean baseline 24-h urinary sodium excretion and kidney failure in the entire cohort and subgroups

Hazard ratios (HRs) (95% CI) were per 1 g/d higher urine sodium, and HRs were log scale. p-int was p-value for the interaction. The hazard ratios were adjusted for age, sex, race, cause of kidney disease, measure GFR, log urine protein, BMI, SBP, LDL cholesterol, HDL cholesterol, smoking, diabetes, history of CVD, ACE inhibitor use, diuretic use, MDRD study A or B, and randomization to blood pressure and dietary protein target.

Figure 3. Unadjusted and adjusted restricted cubic splines for mean baseline 24-h urinary sodium excretion and kidney failure stratified by baseline proteinuria

Splines were plotted using 4 default knots. p-value for nonlinearity of urine sodium were 0.005 in unadjusted model and 0.003 in adjusted model. Thin dashed lines indicate 95% CIs, and rugs at the bottom and top showed location of each value for 24-h urine sodium in those with baseline urine protein < 1g/d and ≥ 1 g/d, respectively. Splines were adjusted for age, sex, race, cause of kidney disease, measure GFR, log urine protein, BMI, SBP, LDL cholesterol, HDL cholesterol, smoking, diabetes, history of CVD, ACE inhibitor use, diuretic use, MDRD study A or B, and randomization to blood pressure and dietary protein target, and interaction between urine sodium and baseline urine protein.