Albuminuria reduced by SGLT2i in CKD patients with and without T2DM

Introduction and methods

Aim of the study

Early lowering of albuminuria is associated with a reduced risk of kidney failure [1]. Therefore, albuminuria can be used as a surrogate for kidney failure. The DAPA-CKD trial showed that dapagliflozin reduced the rate of progressive chronic kidney disease, CV death or HF hospitalization, and all-cause mortality investigated in chronic kidney disease (CKD) patients with and without T2DM [2]. In this prespecified analysis of the DAPA-CKD trial, the effects of dapagliflozin on albuminuria were investigated in patients with and without T2DM. Furthermore, the association between early changes in albuminuria and long-term changes in kidney function was assessed.

Study design

The DAPA-CKD trial was a double-blind, randomized, placebo-controlled trial of 4304 patients with CKD, defined as an eGFR of 25-75 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio (UACR) of 200-5000 mg/g. Patients with and without T2DM were included and all patients were on stable ACEi or ARB treatment. They were randomized (1:1) to dapagliflozin or matched placebo. Median on-treatment follow-up was 2.3 years (IQR 1.8-2.6) and the trial was stopped because the primary endpoint was met.

Outcomes

The prespecified outcome was the mean change in log-transformed UACR from baseline to the end of the study. Furthermore, progression in UACR stage was defined as the initial development of nephrotic range albuminuria (UACR ≥3000 mg/g) and regression in UACR stage as the initial transition from macroalbuminuria (UACR ≥300 mg/g) to microalbuminuria or normoalbuminuria (UACR <300 mg/g).

Main results

• The geometric mean percentage change in UACR with dapagliflozin compared to placebo was -26.5% (95%CI:-22.1 to -30.9%, P<0.0001) at week 2. During follow-up, this was -29.3% (95%CI:-33.1 to -25.2%, P<0.0001).
• Treatment with dapagliflozin resulted in a geometric mean percentage change of -35.1% (95%CI:-39.4 to -30.6%, P<0.0001) in patients with type 2 diabetes and -14.8% (95%CI:-22.9 to -5.9%, P=0.0016) in patients without T2DM at follow-up (Pinteraction<0.0001).
• Effects of dapagliflozin compared with placebo on UACR were larger in patients with diabetic nephropathy compared with other causes of CKD.
• The effect of dapagliflozin on UACR was more pronounced in patients with poorer glycemic control.
• Effects of dapagliflozin on UACR were consistent across the spectrum of baseline UACR and eGFR.
• Treatment with dapagliflozin increased the likelihood of regression in UACR stage (HR 1.81, 95%CI:1.60-2.05), in patients with T2DM (HR 2.06, 95%CI:1.78-2.39) and patients without T2DM (HR 1.33, 95%CI:1.0-1.66) with a more pronounced effect in patients with T2DM (Pinteraction=0.0011).
• Treatment with dapagliflozin reduced the likelihood of progression in UACR stage (HR 0.41, 95%CI:0.32-0.52) with no difference between patients with T2DM and without T2DM.
• Large acute declines in eGFR 2 weeks after randomization were associated with a larger reduction in UACR at day 14 (β=0.25, P<0.0001)
• Larger reductions in UACR at week 2 were associated with less steep declines in eGFR over time (β=3.06, P=0.0056).

Conclusion

References

Find this article online at Lancet Diabetes Endocrinol