No abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Background Low muscle mass likely results in reduced capacity for glucose disposal, leading to a significant but under-appreciated contribution to increasing the risk of diabetes. But few prospective studies have investigated the association between the loss of muscle mass and the occurrence of diabetes. We aimed to investigate whether short-term changes in muscle mass affect the incidence of diabetes in a Chinese population. Methods This study included 1275 individuals without evident diabetes at baseline. In the baseline and re-examination, individuals completed the risk factors survey and underwent body composition measurement. Muscle mass index was defined as the percentage skeletal muscle mass, which was measured by an automatic bioelectric analyzer. Results After a median follow-up of 2.1 years, 142 individuals developed diabetes (11.1%). There was an inverse association between basal skeletal muscle mass index and the risk of diabetes in participants with impaired glucose regulation but not in those with normal glucose tolerance. Multivariate-adjusted hazard ratios for the risk of developing diabetes were 0.85 (95% CI: 0.74–0.98) and 1.15 (95% CI: 0.98–1.34), respectively. Furthermore, Cox regression analysis revealed that a two-year change in skeletal muscle mass was also inversely associated with the incidence of diabetes in both participants with normal glucose tolerance and with impaired glucose regulation (HR: 0.76, 95% CI: 0.65–0.89; HR: 0.81, 95% CI: 0.71–0.91). Conclusions These findings emphasized the importance of early detection and control of muscle mass loss for the prevention of diabetes.