Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most promising candidate biomarkers of renal injury, with expression in renal tissue increasing dramatically after ischemia-reperfusion injury but not in the case of pure pre-renal failure. In a recent issue of Critical Care, Di Somma and colleagues reported that NGAL could improve the classification of acute kidney injury compared with clinical assessment and showed that NGAL was associated with poor prognosis. NGAL may therefore carry different information than biomarkers of renal function. This study finally provides additional evidence for the highly complex relationship between renal function and renal injury.

Background

Acute kidney injury (AKI) is one of the most frequent organ failure encountered among intensive care unit patients. In addition to the well-known immediate complications (hydroelectrolytic disorders, hypervolemia, drug overdose), the occurrence of long-term complications and/or chronic comorbidities related to AKI has long been underestimated. The aim of this manuscript is to briefly review the short- and long-term consequences of AKI and discuss strategies likely to improve outcome of AKI.

Main body

We reviewed the literature, focusing on the consequences of AKI in all its aspects and the management of AKI. We addressed the importance of clinical management for improving outcomes AKI. Finally, we have also proposed candidate future strategies and management perspectives.

Conclusion

AKI must be considered as a systemic disease. Due to its short- and long-term impact, measures to prevent AKI and limit the consequences of AKI are expected to improve global outcomes of patients suffering from critical illnesses.

PURPOSE OF REVIEW: There is an important need for improved diagnostic strategies and treatment among patients with acute kidney injury (AKI). Classical randomized clinical trials have generated relevant results in AKI but are associated with shortcomings, such as high costs and sometimes lack of generalizability. In this minireview, we discuss the value and limits of pragmatic trials and platform trials for AKI research. RECENT FINDINGS: The implementation of pragmatic and platform trials in critical care settings has generated relevant clinical evidence impacting clinical practice. Pragmatic and platform designs have recently been applied to patients at risk of AKI and represent a crucial opportunity to advance our understanding of optimized treatment and strategies in patients at risk of AKI or presenting with AKI. Trials embedded in electronic health records can facilitate patient enrollment and data collection. Platform trials have allowed for a more efficient study design. Although both pragmatic and platform trials have several advantages, they also come with the challenges and shortcomings discussed in this review. SUMMARY: Pragmatic and platform trials can provide clinical answers in real-life settings, facilitate a significant sample size enrollment at a limited cost, and provide results that can have a faster implementation in clinical practice.

Complex interrelations exist between the master central clock, located in the suprachiasmatic nuclei of the hypothalamus, and several peripheral clocks, such as those found in different immune cells of the body. Moreover, external factors that are called 'timekeepers', such as light/dark and sleep/wake cycles, interact with internal clocks by synchronizing their different oscillation phases. Chronobiology is the science that studies biologic rhythms exhibiting recurrent cyclic behavior. Circadian rhythms have a duration of approximately 24 h and can be assessed through chronobiologic analysis of time series of melatonin, cortisol, and temperature. Critically ill patients experience severe circadian deregulation due to not only the lack of effective timekeepers in the intensive care unit (ICU) environment but also systemic inflammation. The latter has been found in both animal and human studies to disrupt circadian rhythmicity of all measured biomarkers. The aims of this article are to describe circadian physiology during acute stress and to discuss the effects of ICU milieu upon circadian rhythms, in order to emphasize the value of considering circadian-immune disturbance as a potential tool for personalized treatment. Thus, besides neoplastic processes, critical illness could be linked to what has been referred as 'chronomics': timing and rhythm. In addition, different therapeutic perspectives will be presented in association with environmental approaches that could restore circadian connection and hasten physical recovery.

The renin-angiotensin system (RAS) plays a crucial role in regulating blood pressure and the cardio-renal system. The classical RAS, mainly mediated by angiotensin I, angiotensin-converting enzyme, and angiotensin II, has been reported to be altered in critically ill patients, such as those in vasodilatory shock. However, recent research has highlighted the role of some components of the counterregulatory axis of the classical RAS, termed the alternative RAS, such as angiotensin-converting Enzyme 2 (ACE2) and angiotensin-(1-7), or peptidases which can modulate the RAS like dipeptidyl-peptidase 3, in many critical situations. In cases of shock, dipeptidyl-peptidase 3, an enzyme involved in the degradation of angiotensin and opioid peptides, has been associated with acute kidney injury and mortality and preclinical studies have tested its neutralization. Angiotensin-(1-7) has been shown to prevent septic shock development and improve outcomes in experimental models of sepsis. In the context of experimental acute lung injury, ACE2 activity has demonstrated a protective role, and its inactivation has been associated with worsened lung function, leading to the use of active recombinant human ACE2, in preclinical and human studies. Angiotensin-(1-7) has been tested in experimental models of acute lung injury and in a recent randomized controlled trial for patients with COVID-19 related hypoxemia. Overall, the alternative RAS appears to have a role in the pathogenesis of disease in critically ill patients, and modulation of the alternative RAS may improve outcomes. Here, we review the available evidence regarding the methods of analysis of the RAS, pathophysiological disturbances of this system, and discuss how therapeutic manipulation may improve outcomes in the critically ill.

After publication of the original article [1], we were notified that an author's name has been incorrectly spelled. Author's first name is Hafid and the family name is Ait-Oufella (with a hyphen between Ait and Oufella). The original article has been corrected.

PURPOSE:To review the mechanisms of action, expected efficacy and side effects of strategies to control hyperkalemia in acutely ill patients. METHODS:We searched MEDLINE and EMBASE for relevant papers published in English between Jan 1, 1938, and July 1, 2018, in accordance with the PRISMA Statement using the following terms: "hyperkalemia," "intensive care," "acute kidney injury," "acute kidney failure," "hyperkalemia treatment," "renal replacement therapy," "dialysis," "sodium bicarbonate," "emergency," "acute." Reports from within the past 10 years were selected preferentially, together with highly relevant older publications. RESULTS:Hyperkalemia is a potentially life-threatening electrolyte abnormality and may cause cardiac electrophysiological disturbances in the acutely ill patient. Frequently used therapies for hyperkalemia may, however, also be associated with morbidity. Therapeutics may include the simultaneous administration of insulin and glucose (associated with frequent dysglycemic complications), β-2 agonists (associated with potential cardiac ischemia and arrhythmias), hypertonic sodium bicarbonate infusion in the acidotic patient (representing a large hypertonic sodium load) and renal replacement therapy (effective but invasive). Potassium-lowering drugs can cause rapid decrease in serum potassium level leading to cardiac hyperexcitability and rhythm disorders. CONCLUSIONS:Treatment of hyperkalemia should not only focus on the ability of specific therapies to lower serum potassium level but also on their potential side effects. Tailoring treatment to the patient condition and situation may limit the risks.