#236 Immediate or delayed initiation of renal replacement therapy in patients with leptospirosis and acute kidney injury: a target trial emulation

Abstract

Abstract Background and Aims Leptospirosis is a widespread zoonosis responsible for 60,000 deaths annually worldwide [1]. Acute kidney injury (AKI) stands out as a hallmark of the disease. Leptospirosis-induced AKI (AKI-L) has been entertained as a potential cause of chronic kidney injury of unknown etiology, which is a significant burden in tropical rural settings [2]. Anecdotal evidence suggests that early renal replacement therapy (RRT) may improve mortality associated with AKI-L [3]. Conversely, several randomized controlled trials (RCTs) conducted in intensive care units have refuted the positive impact of early RRT on mortality in patients with other causes of AKI and sepsis [4]. Given these contradicting results, the optimal timing for initiating RRT in patients with leptospirosis and severe AKI remains uncertain. In this emulated RCT, we aimed to evaluate the impact of the timing of RRT on mortality and worsening renal failure (WRF) in patients hospitalized with leptospirosis, stage 3 AKI on admission, and no immediate need for RRT. Method We conducted a retrospective cohort study in two academic centers in Réunion island between 2010 and 2020. During this period, we included adult patients with documented leptospirosis and stage 2 or 3 AKI. Then we selected patients with stage 3 AKI to perform a target trial emulation, adapted from the AKIKI trial's design. Patients were categorized according to the allocated treatment strategy. Patients assigned to the “early” group received RRT within 48 hours following hospital admission while patients in the “delayed” group did not. A propensity score was derived for each imputed dataset using multivariate logistic regression. The propensity score estimates the probability of treatment allocation as a function of covariates assessed upon hospital entry. These covariates included those used in the SAPSII score and patients' baseline renal function. The primary outcome was a composite outcome assessed at one year: death or WRF. Results The cohort included 380 patients. We selected 295 patients with stage 3 AKI to perform the emulated RCT. Eight two (28%) patients were started on RRT within 48 hours of admission and were assigned to the early group. The delayed group included the remaining 213 patients, with 25% undergoing subsequent RRT and 75% not requiring such intervention. The median time to RRT initiation was 2 (1-3) days. Fifty-nine patients (20%) met the primary outcome: 14 patients (4.7%) died during their hospital stay or within 1 year after discharge, and 45 (15.3%) developed WRF. In the main analysis, the adjusted odds ratio (OR) for primary outcome occurrence was of 2.12 (95% confidence interval: 1.03 to 4.37, p = 0.04; reference group: “delayed” strategy). In secondary analyses, there was a significantly higher probability of WRF at one year in patients assigned to the “early strategy” (OR = 2.79 [1.28-6.11], p = 0.010). Mortality at one year according to RRT timing strategy did not differ (p = 0.6). Conclusion Early initiation of RRT was not found to improve the combined outcome of death and development of WRF in patients with leptospirosis and stage 3 AKI. A strategy based on a delayed initiation of RRT should be formally recommended for patients with severe AKI-L as in the general population of critically ill patients.