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
Analysis (n=4304) found dapaglifozin significantly reduced albuminuria (urinary albumin-to-creatinine ratio reduced by 29.3% vs placebo; p<0.0001), with a larger relative reduction in those with type 2 diabetes (-35.1%, p<0.0001) vs. those without (-14.8%, p=0.0016).
Source:
The Lancet Diabetes & Endocrinology
SPS commentary:
In those with a urinary albumin-to-creatinine ratio (UACR) 300 mg/g or greater, dapaglifozin increased the likelihood of regression to an improved UACR stage vs placebo (HR 1.81, 95%CI 1.60 to 2.05). In those with UACR <3000mg/g, dapagliflozin decreased the risk of progression to worse UACR stage (HR 0.41, 95%CI 0.32 to 0.52).
A separate analysis of this RCT found dapagliflozin significantly slowed eGFR decline vs placebo (by 0.95mL/min/1.73m2/year; 95%CI 0.63-1.27). Difference in eGFR slope compared to placebo was greater in type 2 diabetes, and with higher HbA1c and urinary albumin-to-creatinine ratio. A greater difference in eGFR slope vs placebo indicates a more significant treatment effect.
A related commentary discusses these studies and provides context for this new evidence. The authors suggest eGFR slope may be a feasible endpoint for new CKD trials, especially for interventions at earlier stages of chronic kidney disease, when occurrence of CKD events as endpoints is less feasible. They also state coupling clinical trials based on eGFR slope as a primary outcome for regulatory approval with a longer-term follow-up study of clinical kidney disease events and safety outcomes to maintain ongoing approval could be a way forward for new therapeutic agents. They conclude now that the evidence is clear for the lifesaving and health-preserving benefits of new chronic kidney disease therapies, the health-care community must squarely focus on dissemination and implementation to provide therapeutic access to the enormous number of people worldwide who stand to benefit.