Dapagliflozin reduces albuminuria in CKD patients with or without diabetes: Lancet study
USA: A prespecified analysis from the DAPA-CKD trial has found that the SGLT2 inhibitor dapagliflozin significantly reduces albuminuria in patients with chronic kidney disease (CKD) with and without type 2 diabetes (T2D). However, a larger relative reduction was observed in patients with type 2 diabetes. The study results are published in the journal The Lancet Diabetes and Endocrinology.
"Dapagliflozin imposed similar effects on clinical outcomes in patients with or without T2D but different effects on the urinary albumin-to-creatinine ratio (UACR)," wrote Niels Jongs, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands, and colleagues. "This suggests that part of the protective effect of dapagliflozin in CKD patients might be medicated through pathways unrelated to albuminuria reduction."
Previous studies have shown albuminuria to be associated with a lower risk of kidney failure in CKD patients. Dapagliflozin is known to significantly reduce albuminuria in patients with type 2 diabetes and normal or near-normal kidney function. However, it is not known whether this effect persists in patients with CKD with and without T2D. To fill this knowledge gap, Dr. Jongs, and the team the effects of dapagliflozin on albuminuria in patients with chronic kidney disease with and without type 2 diabetes in the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial.
DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomized trial done performed at 386 sites in 21 countries. It included 4304 patients having chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) between 25 mL/min per 1·73 m2 and 75 mL/min per 1·73 m2 and a urinary albumin-to-creatinine ratio (UACR) between 200 mg/g and 5000 mg/g (22·6 to 565·6 mg/mmol). They were randomly assigned in the ratio of 1:1 to receive dapagliflozin 10 mg (AstraZeneca; Gothenburg, Sweden) (n= 2152) or once daily or a matching placebo (n=2152).
Change in albuminuria was a pre-specified exploratory outcome of DAPA-CKD. Regression in the UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to microalbuminuria or normoalbuminuria (<300 mg/g), and progression in the UACR stage, defined as a transition from less than 3000 mg/g to 3000 mg/g or greater, were additional discrete endpoints.
Key findings include:
- Compared with placebo, dapagliflozin reduced geometric mean UACR by 29·3%; relative to placebo, treatment with dapagliflozin resulted in a geometric mean percentage change of −35·1% in patients with type 2 diabetes and −14·8% in patients without type 2 diabetes over the follow-up visits.
- Among 3860 patients with UACR of 300 mg/g or greater at baseline, dapagliflozin increased the likelihood of regression in UACR stage (hazard ratio 1·81).
- Among 3820 patients with UACR less than 3000 mg/g at baseline, dapagliflozin decreased the risk of progression in UACR stage (0·41, 0·32 to 0·52).
- Larger reductions in UACR at day 14 during dapagliflozin treatment were significantly associated with attenuated eGFR decline during subsequent follow-up (β per log unit UACR change –3·06).
The researchers concluded, "the findings suggest that part of the protective effect of dapagliflozin in patients with chronic kidney disease might be mediated through pathways unrelated to reduction in albuminuria."
Reference:
The study titled, "Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial," is published in the journal The Lancet Diabetes and Endocrinology.
DOI: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00243-6/fulltext
