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.

Sodium‐glucose co‐transporter 2 inhibitor therapy: use in chronic kidney disease and adjunctive sodium restriction

“…The study is a retrospective analysis of a randomised trial investigating the antihypertensive and anti-albuminuric effects of dapagliflozin in Japanese individuals with albuminuric DKD. 42 Participants with a higher basal sodium intake experienced greater improvements in home BP profile than those with a lower basal sodium intake. There was no difference between groups in terms of improvements in albuminuria.…”

“…43 Moreover, participants' sodium intake was not controlled during the study. 42 Additionally, given the retrospective nature of the study, it is difficult to establish causal relationships between participants' basal sodium intake and the effects of dapagliflozin on BP and albuminuria.…”

“…To our knowledge, only one study has evaluated the impact of dietary sodium intake on the effects of SGLT2 inhibition in humans. The study is a retrospective analysis of a randomised trial investigating the antihypertensive and anti‐albuminuric effects of dapagliflozin in Japanese individuals with albuminuric DKD 42 . Participants with a higher basal sodium intake experienced greater improvements in home BP profile than those with a lower basal sodium intake.…”

“…However, estimations of sodium intake were based on a single spot urine sample rather than a series of 24‐h urine samples, which more accurately reflect daily sodium intake 43 . Moreover, participants' sodium intake was not controlled during the study 42 . Additionally, given the retrospective nature of the study, it is difficult to establish causal relationships between participants' basal sodium intake and the effects of dapagliflozin on BP and albuminuria.…”

Novel insights in classic versus relative glomerular hyperfiltration and implications on pharmacotherapy

“…As SGLT-2 inhibitors reduce afferent arteriole vasodilation, they provide a reno-protective pathway complementary to the efferent arteriole vasodilation induced by RAS blockade [79 ▪▪ ]. Using a mouse model, there were no effects on hyperfiltration or progression of renal injury in hypervolemic kidney disease models, suggesting that high salt intake and extracellular volume might attenuate the protective effects of SGLT-2 blockers [80 ▪▪ ].…”