Effects of dapagliflozin on volume status and systemic haemodynamics in patients with chronic kidney disease without diabetes: Results from DAPASALT and DIAMOND.
Diabetes Obes Metab
; 24(8): 1578-1587, 2022 08.
Article
en En
| MEDLINE
| ID: mdl-35478433
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 ANDMETHODS:
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 m2 , median urine albumincreatinine 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 m2 , 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Insuficiencia Renal Crónica
/
Inhibidores del Cotransportador de Sodio-Glucosa 2
Tipo de estudio:
Clinical_trials
Límite:
Aged
/
Humans
/
Middle aged
Idioma:
En
Revista:
Diabetes Obes Metab
Asunto de la revista:
ENDOCRINOLOGIA
/
METABOLISMO
Año:
2022
Tipo del documento:
Article
País de afiliación:
Países Bajos