Relationship between basal sodium intake and the effects of dapagliflozin in albuminuric diabetic kidney disease

Abstract

We investigated the impact of basal dietary sodium intake on the dapagliflozin-induced changes in albuminuria and blood pressure (BP) measured at home in patients with diabetic kidney disease (DKD).This was a secondary analysis of the Y-AIDA Study, in which DKD patients with estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73 m² and urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine were administered dapagliflozin for 24 weeks, and dapagliflozin significantly improved albuminuria levels and home BP profiles. The effects on UACR, home-measured BP, and eGFR were compared between high- and low-sodium intake groups (HS and LS groups), which were created using baseline urinary sodium-to-creatinine ratio of 84 participants with available basal sodium-to-creatinine ratios. At baseline, clinic-/home-measured BPs, UACR, and eGFR, were comparable in the two groups. After 24 weeks, the reductions from baseline in ln-UACR were comparable in the two groups. In contrast, the reductions in evening home systolic BP and eGFR from baseline were larger in HS than in LS (BP: - 13 ± 2.08 vs. - 6 ± 1.88, P = 0.020; eGFR: - 3.33 ± 1.32 vs. 0.37 ± 1.29, P = 0.049). The home BP-lowering effects of dapagliflozin are larger in HS than LS, concomitant with a larger reduction in eGFR, suggesting a dapagliflozin-induced improvement in glomerular relative hyperfiltration in HS.

Figure 1

Effects of add-on dapagliflozin therapy on renal endpoints in the HS and LS groups. (a) Natural logarithm of urine albumin-to-creatinine ratio (ln-UACR), and (b) estimated glomerular filtration (eGFR) in dapagliflozin-treated patients during the 24-week study period. Change in (c) ln-UACR, and (d) eGFR during the 24-week study period. Eighty-four DKD patients were allocated to a high sodium intake (HS) group (open square) or a low sodium intake (LS) group (filled square), according to their median urinary sodium-to-creatinine ratio at baseline. Values are mean ± SE. The differences in the effects of dapagliflozin treatment between the two groups were analyzed using unpaired t-tests at each visit. NS not significant.

Figure 2

Effects of add-on dapagliflozin therapy on the glucose metabolism, clinic-measured blood pressure, body mass, and body mass index of the HS and LS groups. (a) HbA1c, (c) fasting blood glucose (FBG), (e) clinic systolic blood pressure (SBP), (g) clinic diastolic blood pressure (DBP), (i) body mass, and (k) body mass index (BMI) in dapagliflozin-treated patients during the 24-week study period. Change in (b) HbA1c, (d) FBG, (f) clinic SBP, (h) clinic DBP, (j) body mass, and (l) BMI during the 24-week study period. Eighty-four DKD patients were allocated to a high sodium intake (HS) group (open square) or a low sodium intake (LS) group (filled square), according to their median urinary sodium-to-creatinine ratio at baseline. Values are mean ± SE. The differences in the effects of dapagliflozin treatment between the two groups were analyzed using unpaired t-tests at each visit. NS, not significant.

Figure 3

Effects of add-on dapagliflozin therapy on home-measured blood pressure in the HS and LS groups. Home blood pressure (BP) ((a) morning systolic BP (SBP), (c) morning diastolic BP (DBP), (e) evening SBP, (g) evening DBP, (i) nocturnal SBP, and (k) nocturnal DBP) in dapagliflozin-treated patients during the 24-week study period. Change in home BP ((b) morning SBP, (d) morning DBP, (f) evening SBP, (h) evening DBP, (j) nocturnal SBP, and (l) nocturnal DBP) during the 24-week study period. Eighty-four DKD patients were allocated to a high sodium intake (HS) group (open square) or a low sodium intake (LS) group (filled square), according to their median urinary sodium-to-creatinine ratio at baseline. Values are mean ± SE. The differences in the effects of dapagliflozin treatment between the two groups were analyzed using unpaired t-tests. NS, not significant.

Figure 4

Effects of add-on dapagliflozin therapy on renal endpoints and home-measured blood pressure in the high salt intake and low salt intake groups based on the Tanaka formula. Change in (a) natural logarithm of urine albumin-to-creatinine ratio (ln-UACR), and (b) estimated glomerular filtration (eGFR) during the 24-week study period. Change in home blood pressure (BP) ((c) morning systolic BP (SBP), (d) evening SBP, and (e) nocturnal SBP) during the 24-week study period. Eighty-four DKD patients were allocated to the high salt intake group (open square) or low salt intake group (filled square), according to median estimated daily salt intake calculated using the Tanaka formula at baseline. Values are presented as mean ± SE. Differences in the effects of dapagliflozin treatment between the two groups were analyzed using unpaired t-tests at each visit. NS not significant.