Effects of dapagliflozin on volume status and systemic haemodynamics in patients with chronic kidney disease without diabetes: Results from DAPASALT and DIAMOND.

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 100883645 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1463-1326 (Electronic) Linking ISSN: 14628902 NLM ISO Abbreviation: Diabetes Obes Metab Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford : Wiley-Blackwell, c1999-
    • Subject Terms:
      Diabetes Mellitus, Type 2*/drug therapy ; Renal Insufficiency, Chronic*/complications ; Renal Insufficiency, Chronic*/drug therapy ; Sodium-Glucose Transporter 2 Inhibitors*/pharmacology ; Sodium-Glucose Transporter 2 Inhibitors*/therapeutic use; Aged ; Aldosterone ; Benzhydryl Compounds/pharmacology ; Benzhydryl Compounds/therapeutic use ; Biomarkers ; Blood Pressure ; Glomerular Filtration Rate ; Glucose/pharmacology ; Glucosides ; Humans ; Middle Aged ; Renin ; Sodium
    • Abstract:
      Aims: To assess the effect of sodium-glucose cotransporter-2 inhibitor dapagliflozin on natriuresis, blood pressure (BP) and volume status in patients with chronic kidney disease (CKD) without diabetes.
      Materials and Methods: We performed a mechanistic open-label study (DAPASALT) to evaluate the effects of dapagliflozin on 24-hour sodium excretion, 24-hour BP, extracellular volume, and markers of volume status during a standardized sodium diet (150 mmol/d) in six patients with CKD. In parallel, in a placebo-controlled double-blind crossover trial (DIAMOND), we determined the effects of 6 weeks of dapagliflozin on markers of volume status in 53 patients with CKD.
      Results: In DAPASALT (mean age 65 years, mean estimated glomerular filtration rate [eGFR] 39.4 mL/min/1.73 m 2 , median urine albumin:creatinine ratio [UACR] 111 mg/g), dapagliflozin did not change 24-hour sodium and volume excretion during 2 weeks of treatment. Dapagliflozin was associated with a modest increase in 24-hour glucose excretion on Day 4, which persisted at Day 14 and reversed to baseline after discontinuation. Mean 24-hour systolic BP decreased by -9.3 (95% confidence interval [CI] -19.1, 0.4) mmHg after 4 days and was sustained at Day 14 and at wash-out. Renin, angiotensin II, urinary aldosterone and copeptin levels increased from baseline. In DIAMOND (mean age 51 years, mean eGFR 59.0 mL/min/1.73 m 2 , median UACR 608 mg/g), compared to placebo, dapagliflozin increased plasma renin (38.5 [95% CI 7.4, 78.8]%), aldosterone (19.1 [95% CI -5.9, 50.8]%), and copeptin levels (7.3 [95% CI 0.1, 14.5] pmol/L).
      Conclusions: During a standardized sodium diet, dapagliflozin decreased BP but did not increase 24-hour sodium and volume excretion. The lack of increased natriuresis and diuresis may be attributed to activation of intra-renal compensatory mechanisms to prevent excessive water loss.
      (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
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    • Grant Information:
      P30 DK048520 United States DK NIDDK NIH HHS; P30 DK116073 United States DK NIDDK NIH HHS; R21 DK129720 United States DK NIDDK NIH HHS; K23 DK116720 United States DK NIDDK NIH HHS; R01 DK129211 United States DK NIDDK NIH HHS
    • Contributed Indexing:
      Keywords: SGLT2 inhibitor; adaptive response; dapagliflozin; kidney
    • Accession Number:
      0 (Benzhydryl Compounds)
      0 (Biomarkers)
      0 (Glucosides)
      0 (Sodium-Glucose Transporter 2 Inhibitors)
      1ULL0QJ8UC (dapagliflozin)
      4964P6T9RB (Aldosterone)
      9NEZ333N27 (Sodium)
      EC 3.4.23.15 (Renin)
      IY9XDZ35W2 (Glucose)
    • Publication Date:
      Date Created: 20220428 Date Completed: 20220708 Latest Revision: 20230608
    • Publication Date:
      20240628
    • Accession Number:
      PMC9262818
    • Accession Number:
      10.1111/dom.14729
    • Accession Number:
      35478433