Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.

中文翻译：

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急性肾损伤 (STARRT-AKI) 试验中标准与加速启动肾脏替代治疗的贝叶斯再分析

危重患者开始肾脏替代治疗 (KRT) 的时间仍然存在争议。急性肾损伤中肾替代治疗的标准与加速启动 (STARRT-AKI) 试验比较了急性肾损伤危重患者的两种 KRT 启动策略（加速与标准），并发现 90 天全因治疗的中性结果死亡。对试验终点的概率探索可能有助于更好地理解试验结果。我们的目标是使用贝叶斯框架进行再分析。我们对在 15 个国家的 168 个中心进行的多国 STARRT-AKI 试验中随机分配的所有 2927 名患者进行了二次分析。使用分级贝叶斯逻辑回归评估主要终点，即 90 天全因死亡率。一系列先验包括乐观、中立和悲观的先验，以及从早期临床试验中获悉的先验。次要终点（无 KRT 天数和无医院天数）使用零-一膨胀 β 回归进行评估。比较加速与标准 KRT 启动策略的主要终点获益的后验概率表明，无论先前使用如何，都没有显着差异（绝对差异为 0.13% [95% 可信区间 [CrI] - 3.30%; 3.40%]， − 0.39% [95% CrI − 3.46%; 3.00%] 和 0.64% [95% CrI − 2.53%; 3.88%] 分别用于中性、乐观和悲观先验）。效果大小等于或大于共识定义的最小临床重要差异的可能性非常低。分配到加速策略的患者无 KRT 天数较少（中位绝对差异为 - 3.55 天 [95% CrI - 6.38; - 0.48]），加速策略可能与更多无 KRT 天数相关0.008。策略之间的住院天数相似，与标准策略相比，加速策略的住院天数中位数绝对差异多 0.48 (95% CrI − 1.87; 2.72)，并且加速策略具有更多住院天数的概率空闲天数为 0.66。在对 STARRT-AKI 试验的贝叶斯再分析中，我们发现与标准策略相比，加速策略具有临床重要益处的可能性非常低。接受加速策略的患者可能存活的天数更少并且没有 KRT。