Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Population Health Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Kidney Int. 2024 Oct;106(4):688-698. doi: 10.1016/j.kint.2024.05.024. Epub 2024 Jun 18.
Pharmacologic interventions to slow chronic kidney disease progression, such as ACE-inhibitors, angiotensin receptor blockers, or sodium glucose co-transporter 2 inhibitors, often produce acute treatment effects on glomerular filtration rate (GFR) that differ from their long-term chronic treatment effects. Observational studies assessing the implications of acute effects cannot distinguish acute effects from GFR changes unrelated to the treatment. Here, we performed meta-regression analysis of multiple trials to isolate acute effects to determine their long-term implications. In 64 randomized controlled trials (RCTs), enrolling 154,045 participants, we estimated acute effects as the mean between-group difference in GFR slope from baseline to three months, effects on chronic GFR slope (starting at three months after randomization), and effects on three composite kidney endpoints defined by kidney failure (GFR 15 ml/min/1.73m or less, chronic dialysis, or kidney transplantation) or sustained GFR declines of 30%, 40% or 57% decline, respectively. We used Bayesian meta-regression to relate acute effects with treatment effects on chronic slope and the composite kidney endpoints. Overall, acute effects were not associated with treatment effects on chronic slope. Acute effects were associated with the treatment effects on composite kidney outcomes such that larger negative acute effects were associated with lesser beneficial effects on the composite kidney endpoints. Associations were stronger when the kidney composite endpoints were defined by smaller thresholds of GFR decline (30% or 40%). Results were similar in a subgroup of interventions with supposedly hemodynamic effects that acutely reduce GFR. For studies with GFR 60 mL/min/1.73m or under, negative acute effects were associated with larger beneficial effects on chronic GFR slope. Thus, our data from a large and diverse set of RCTs suggests that acute effects of interventions may influence the treatment effect on clinical kidney outcomes.
药理干预措施可减缓慢性肾脏病进展，如血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂或钠-葡萄糖共转运蛋白 2 抑制剂，通常对肾小球滤过率（GFR）产生急性治疗效果，与长期慢性治疗效果不同。评估急性效果影响的观察性研究无法区分急性效果与与治疗无关的 GFR 变化。在这里，我们对多项试验进行了荟萃回归分析，以分离急性效果，确定其长期意义。在 64 项随机对照试验（RCT）中，纳入了 154045 名参与者，我们估计急性效果为从基线到三个月时 GFR 斜率的组间平均差异，对慢性 GFR 斜率的影响（从随机分组后三个月开始），以及通过肾脏衰竭（GFR 15 ml/min/1.73m 或更低、慢性透析或肾脏移植）或 GFR 持续下降 30%、40%或 57%定义的三个复合肾脏终点的影响，分别。我们使用贝叶斯荟萃回归将急性效果与慢性斜率和复合肾脏终点的治疗效果相关联。总体而言，急性效果与慢性斜率的治疗效果无关。急性效果与复合肾脏终点的治疗效果相关，即更大的负急性效果与复合肾脏终点的较小获益效果相关。当肾脏复合终点由较小的 GFR 下降阈值（30%或 40%）定义时，关联更强。在具有急性降低 GFR 的假定血流动力学作用的干预措施亚组中，结果相似。对于 GFR 为 60 mL/min/1.73m 或以下的研究，负急性效果与慢性 GFR 斜率的更大获益效果相关。因此，我们从大量和多样化的 RCT 中获得的数据表明，干预措施的急性效果可能会影响临床肾脏结局的治疗效果。
