Dapagliflozin reduces kidney failure risk in patients with CKD but can result in a reversible acute reduction in eGFR upon treatment initiation. Determinants of this eGFR reduction and its associations with efficacy and safety outcomes are unknown.

The DAPA-CKD trial randomized 4304 adults with CKD and albuminuria to once-daily dapagliflozin 10 mg or placebo, added to standard care. We prespecified an analysis comparing the effects of dapagliflozin among patients who experienced relative reductions in eGFR (>10% or >0%–10%) or an increase in eGFR from baseline to 2 weeks and assessed long-term efficacy and safety thereafter.

A total of 4157 (96.6%) patients had eGFR data available at baseline and at 2 weeks. In the dapagliflozin and placebo groups, 1026 (49.4%) and 494 (23.7%), respectively, experienced an acute reduction in eGFR >10%. Among patients receiving dapagliflozin, those with an acute reduction in eGFR >10% experienced a long-term eGFR decline of –1.58 ml/min per 1.73 m² per year compared with –2.44 and –2.48 ml/min per 1.73 m² per year among those experiencing a less pronounced reduction or increase in eGFR, respectively (P-interaction=0.05). In the placebo group, long-term eGFR decline was –3.27, –3.84, and –3.77 ml/min per 1.73 m² per year for acute eGFR reduction subgroups of >10%, >0%–10%, or increase in eGFR (P-interaction=0.48). Rates of serious adverse events and adverse events of special interest in patients randomized to dapagliflozin were unrelated to the acute eGFR change.

Among patients with CKD and albuminuria treated with dapagliflozin, an acute reduction in eGFR (from baseline to 2 weeks) is not associated with higher rates of CKD progression.

Clinical Trial registration number: A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (Dapa-CKD) NCT03036150.

Dapagliflozin 可降低 CKD 患者的肾衰竭风险，但可导致治疗开始时 eGFR 的可逆性急性降低。这种 eGFR 降低的决定因素及其与疗效和安全性结果的关联尚不清楚。

DAPA-CKD 试验将 4304 名患有 CKD 和白蛋白尿的成年人随机分配到标准治疗中加入每日一次的达格列净 10 mg 或安慰剂。我们预设了一项分析，比较从基线到 2 周 eGFR 相对降低（>10% 或 >0%–10%）或 eGFR 增加的患者中达格列净的效果，并评估其后的长期疗效和安全性。

共有 4157 名 (96.6%) 患者在基线和 2 周时获得了 eGFR 数据。在达格列净组和安慰剂组中，分别有 1026 人 (49.4%) 和 494 人 (23.7%) 的 eGFR 急剧下降 >10%。在接受达格列净治疗的患者中，eGFR 急性降低 >10% 的患者的长期 eGFR 下降幅度为 –1.58 ml/min/1.73 m 2 每年，而 –2.44 和 –2.48 ^ml /min/1.73 m ²每年在那些经历 eGFR 不太明显的减少或增加的人中，分别为（P -interaction = 0.05）。在安慰剂组中，对于急性 eGFR 降低 >10%、>0%–10% 或 eGFR 增加的亚组，长期 eGFR 下降为 –3.27、–3.84 和 –3.77 ml/min/1.73 m 2^每年( P-交互=0.48）。随机接受达格列净治疗的患者的严重不良事件和特别关注的不良事件发生率与急性 eGFR 变化无关。

在接受达格列净治疗的 CKD 和白蛋白尿患者中，eGFR 的急剧降低（从基线到 2 周）与较高的 CKD 进展率无关。

临床试验注册号：评估达格列净对慢性肾脏病 (Dapa-CKD) 患者肾脏结局和心血管死亡率影响的研究 NCT03036150。