Clinical review: Timing of renal replacement therapy

Acute kidney injury is common in intensive care patients and continuous renal replacement therapy is the preferred treatment for this in most centres. Although these techniques have been adopted internationally, there remains significant variation with regard to their clinical application. This is particularly pertinent when one considers that the fundamental questions regarding any treatment, such as initiation, dose and length of treatment, remain a source of debate and have not as yet all been fully answered. In this narrative review we consider the timing of renal replacement therapy, highlighting the relative paucity of high quality data regarding this fundamental question. We examine the role of the usual biochemical criteria as well as conventional clinical indications for commencing renal replacement therapy together with the application of recent classification systems, namely RIFLE and AKIN. We discuss the potential role of biomarkers for acute kidney injury as predictors for the need for renal support and discuss commencing therapy for indications other than acute kidney injury

Clinical review: Patency of the circuit in continuous renal replacement therapy

Premature circuit clotting is a major problem in daily practice of continuous renal replacement therapy (CRRT), increasing blood loss, workload, and costs. Early clotting is related to bioincompatibility, critical illness, vascular access, CRRT circuit, and modality. This review discusses non-anticoagulant and anticoagulant measures to prevent circuit failure. These measures include optimization of the catheter (inner diameter, pattern of flow, and position), the settings of CRRT (partial predilution and individualized control of filtration fraction), and the training of nurses. In addition, anticoagulation is generally required. Systemic anticoagulation interferes with plasmatic coagulation, platelet activation, or both and should be kept at a low dose to mitigate bleeding complications. Regional anticoagulation with citrate emerges as the most promising method

Reduction of D-dimer levels after therapeutic administration of antithrombin in acquired antithrombin deficiency of severe sepsis

INTRODUCTION: In acute disseminated intravascular coagulation, the effect of antithrombin (AT) administration on elevated levels of D-dimer is not well established. In the present study, we report on changes in circulating levels of D-dimer in response to administration of AT in a series of patients with acquired AT deficiency due to severe sepsis. METHODS: Eight consecutive critically ill medical patients presenting with acute disseminated intravascular coagulation associated with severe sepsis/septic shock received a single bolus infusion of AT over 30 minutes, aiming to achieve physiological AT levels. Haemostatic parameters including D-dimer were assessed prior to, 6 and 24 h after AT administration. An average of 42 ± 9 U/kg body weight was infused. RESULTS: Following AT substitution, elevated levels of D-dimer fell whereas AT levels rose. CONCLUSION: These observations support the notion that AT can favourably affect fibrin degradation accompanying disseminated intravascular coagulation of severe sepsis

Fluid management in acute kidney injury

Acute kidney injury (AKI) and fluids are closely linked through oliguria, which is a marker of the former and a trigger for administration of the latter. Recent progress in this field has challenged the physiological and clinical rational of using oliguria as a trigger for the administration of fluid and brought attention to the delicate balance between benefits and harms of different aspects of fluid management in critically ill patients, in particular those with AKI. This narrative review addresses various aspects of fluid management in AKI outlining physiological aspects, the effects of crystalloids and colloids on kidney function and the effect of various resuscitation and de-resuscitation strategies on the course and outcome of AKI.Peer reviewe

Pathophysiology of COVID-19-associated acute kidney injury

Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19 and in those with AKI in non-COVID-related sepsis. Acute tubular injury is common, although it is often mild, despite markedly reduced kidney function. Systemic haemodynamic instability very likely contributes to tubular injury. Despite descriptions of COVID-19 as a cytokine storm syndrome, levels of circulating cytokines are often lower in patients with COVID-19 than in patients with acute respiratory distress syndrome with causes other than COVID-19. Tissue inflammation and local immune cell infiltration have been repeatedly observed and might have a critical role in kidney injury, as might endothelial injury and microvascular thrombi. Findings of high viral load in patients who have died with AKI suggest a contribution of viral invasion in the kidneys, although the issue of renal tropism remains controversial. An impaired type I interferon response has also been reported in patients with severe COVID-19. In light of these observations, the potential pathophysiological mechanisms of COVID-19-associated AKI may provide insights into therapeutic strategies