Advancing diagnostic and therapeutic approaches in patients with acute kidney injury

Abstract

Given the alarming increase in AKI incidence in general, which was further exacerbated during the COVID-19 pandemic, there is an urgent need to invest more effort in improving the diagnosis and treatment approaches in patients with AKI. The drawbacks in the recognition of AKI combined with ineffective KRT have far-reaching consequences - not only for individuals but also for social and medical systems. A selection of critical factors that could improve the outcome of patients with AKI is described in this habilitation thesis. Our research findings showed that the incidence of AKI detected by creatinine changes is much higher than its administrative reporting, even in the context of university hospitals in a high-income country such as Germany. Since AKI leads to significantly higher mortality, even in patients whose the diagnosis was not properly documented, the implementation of an automated analysis of clinical data and amplification of clinical decision support algorithms is highly recommended as this could allow for the earlier detection of AKI and might prevent the development of severe kidney injury that requires KRT. One of the most important issues during CKRT is the anticoagulation protocol, RCA has become the standard of care. However, the variety of RCA protocols still requires optimization. We further outlined that the first crucial step in improvement of the RCA protocol for CKRT is its robust validation in terms of safety and efficacy before its broader implementation in clinical routine. This approach will allow caregivers to adopt possible recommendations and adjust the protocol according to local demands and structures, which may improve the safety for the treated patients treated. Since the pfCa concentration has historically served as a valid marker of the anticoagulation efficacy of RCA, close monitoring of pfCa during CKRT has been recommended. We showed that the association of the pfCa with anticoagulation efficacy during RCA-CKRT might be weaker than expected if a protocol with a fixed and high citrate dose is applied. In addition, we highlight the potential of less intensive pfCa monitoring during RCA-CKRT, which may ultimately save staff and material resources without jeopardizing the treatment efficacy. The metabolic complications of RCA were supposed to be the most important drawback of this anticoagulation approach for CKRT, with citrate accumulation being the most severe one. The human body´s ability to metabolize citrate is limited and compromised during shock and other hypoperfusion states, leading to a higher incidence of citrate accumulation during RCA. However, for some time there were no robust data justifying the strict contraindication of RCA during CKRT in patients with hyperlactatemia. In a previous study, we showed that the incidence of citrate accumulation is relatively low even if RCA-CKRT is applied in the unselected cohort of critically ill patients. Furthermore, in the secondary analysis, we found that even in patients with initially severe hyperlactatemia, the frequency of citrate accumulation was still acceptable and patients with significant lactate clearance had a negligible risk for citrate accumulation, even despite initially elevated lactate concentrations. On the other hand, critically ill patients with initially low lactate levels but increasing lactate concentration as a marker of multiorgan disfunction showed a significantly higher incidence of citrate accumulation. Hence, the collective findings indicate that severe hyperlactatemia should not be considered a strict contraindication for RCA-CKRT, whereas patients with insufficient lactate clearance are at risk for developing citrate accumulation. Like many other ICUs across the world during the COVID-19 pandemic, we experienced a significant increase in patients admitted with AKI requiring CKRT. Significant concerns were raised about the optimal anticoagulation approach during CKRT in critically ill COVID-19 patients. In our study, we reported that the efficacy of RCA during CKRT in COVID-19 patients is comparable – and at least non-inferior – to that found in non-COVID-19 patients. However, we also showed that the incidence of metabolic complications during RCA-CKRT in COVID- 19 patients has a different pattern and might be explained by reduced filter patency and thus by an increased systemic citrate load during the CKRT. Based on these findings, we recommend that special attention should be paid to patients with a circuit life of over 48 hours. Another promising therapeutic approach for critically ill COVID-19 patients was the application of a cytokine adsorber that could be mounted on the CKRT circuit. In our prospective randomized pilot study, we investigated the impact of cytokine adsorption by CytoSorb on the resolution of vasoplegic shock and the course of the disease. Our data showed that CytoSorb adsorption did not improve the resolution of shock compared with patients treated with standard therapy. In addition, there was no significant differences in the mortality rates or catecholamine requirements, or the kinetics of the inflammatory parameters (e.g., IL-6 and CRP) between the groups. While further studies are warranted to examine the clinical effect of cytokine elimination in COVID-19 patients, RCA-CKRT was shown to be a reliable and effective matrix for the future application of other adsorptive devices and filters of any type. In summary, we studied important diagnostic and therapeutic factors that significantly influence the expected short- and long-term outcomes of patients with AKI. An optimal and complex approach to the medical care of patients with AKI is important to reduce the high burden of this common condition on the individual patient in particular, and the healthcare system in general.