Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional ‘surges’ in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. Most patients with COVID-19 have mild symptoms, but about 5% develop severe symptoms, which can include acute respiratory distress syndrome, septic shock, and multiple organ failure. Kidney involvement is frequent, with clinical presentation ranging from mild proteinuria to progressive acute kidney injury (AKI) necessitating renal replacement therapy (RRT). An understanding of the pathophysiology and mechanisms of kidney damage and AKI in the setting of critical illness and COVID-19 is emerging, although further research is needed to identify patients at risk of AKI and to guide management strategies. As no specific treatment options exist for AKI secondary to COVID-19, intensive care is largely supportive. Current approaches to prevention and management of AKI, and identification of potential indications for use of RRT and sequential extracorporeal therapies, are based mainly on clinical experience, and AKI strategies are adapted empirically to patients with COVID-19. International collaborative and cross-disciplinary research is needed to obtain adequate evidence to support current clinical approaches and to develop new approaches to management.

Background: Multi-organ dysfunction in critical illness is common and frequently involves the lungs and kidneys, often requiring organ support such as invasive mechanical ventilation (IMV), renal replacement therapy (RRT) and/or extracorporeal membrane oxygenation (ECMO). Methods:A consensus conference on the spectrum of lung-kidney interactions in critical illness was held under the auspices of the Acute Disease Quality Initiative (ADQI) in Innsbruck, Austria, in June 2018. Through review and critical appraisal of the available evidence, the current state of research, and both clinical and research recommendations were described on the following topics: epidemiology, pathophysiology and strategies to mitigate pulmonary dysfunction among patients with acute kidney injury and/or kidney dysfunction among patients with acute respiratory failure/acute respiratory distress syndrome. Furthermore, emphasis was put on patients receiving organ support (RRT, IMV and/or ECMO) and its impact on lung and kidney function. Conclusion:The ADQI 21 conference found significant knowledge gaps about organ crosstalk between lung and kidney and its relevance for critically ill patients. Lung protective ventilation, conservative fluid management and early recognition and treatment of pulmonary infections were the only clinical recommendations with higher quality of evidence. Recommendations for research were formulated, targeting lung-kidney interactions to improve care processes and outcomes in critical illness.

Discoveries have emerged highlighting the complex nature of the interorgan cross-talk between the kidney and the lung. Vascular rigidity, neurohormonal activation, tissue hypoxia, and abnormal immune cell signaling have been identified as common pathways leading to the development and progression of chronic kidney disease. However, our understanding of the causal relationships between lung injury and kidney injury is not precise. This review discusses a number of features and mechanisms of renal dysfunction in pulmonary disorders in relation to respiratory acidosis, impaired gas exchange, systemic congestion, respiratory support/replacement therapies, and other issues relevant to the clinical care of these patients. Biotrauma due to injurious ventilatory strategies can lead to the release of mediators into the lung, which may then translocate into the systemic circulation and cause end-organ dysfunction, including renal dysfunction. Right ventricular dysfunction and congestive states may contribute to alterations of renal perfusion and oxygenation, leading to diuretic resistance and recurrent hospitalization. In patients with concomitant respiratory failure, noninvasive ventilation represents a promising treatment option for the correction of impaired renal microcirculation and endothelial dysfunction. In patients requiring extracorporeal membrane oxygenation, short- and long-term monitoring of kidney function is warranted, as they are at highest risk of developing acute kidney injury and fluid overload.

Critically ill COVID-19 patients are generally admitted to the ICU for respiratory insufficiency which can evolve into a multiple-organ dysfunction syndrome requiring extracorporeal organ support. Ongoing advances in technology and science and progress in information technology support the development of integrated multi-organ support platforms for personalized treatment according to the changing needs of the patient. Based on pathophysiological derangements observed in COVID-19 patients, a rationale emerges for sequential extracorporeal therapies designed to remove inflammatory mediators and support different organ systems. In the absence of vaccines or direct therapy for COVID-19, extracorporeal therapies could represent an option to prevent organ failure and improve survival. The enormous demand in care for COVID-19 patients requires an immediate response from the scientific community. Thus, a detailed review of the available technology is provided by experts followed by a series of recommendation based on current experience and opinions, while waiting for generation of robust evidence from trials.

Over the past decade, science has greatly advanced our understanding of interdependent feedback mechanisms involving the heart, lung, and kidney. Organ injury is the consequence of maladaptive neurohormonal activation, oxidative stress, abnormal immune cell signaling, and a host of other mechanisms that precipitate adverse functional and structural changes. The presentation of interorgan crosstalk may include an acute, chronic, or acute on chronic timeframe. We review the current, state-of-the-art understanding of cardio-pulmonary-renal interactions and their related pathophysiology, perpetuating nature, and cycles of increased susceptibility and reciprocal progression. To this end, we present a multidisciplinary approach to frame the diverse spectrum of published observations on the topic. Assessment of organ functional reserve and use of biomarkers are valuable clinical strategies to screen and detect disease, assist in diagnosis, assess prognosis, and predict recovery or progression to chronic disease.

The complex nature of single organ failure potentially leading to multiple organ dysfunction syndrome (MODS) in critically ill patients necessitates integrated supportive therapy. Rather than a primary disease, acute kidney injury (AKI) is considered a window to a potentially serious underlying systemic disease, which may partially explain the high morbidity and mortality rates associated with the condition. Renal replacement therapy (RRT) has been routinely used for more than a decade in various intensive care settings and there has also been an increase in the use of extracorporeal membrane oxygenation and extracorporeal carbon dioxide removal. When these renal and cardiopulmonary modalities are used together, a multidisciplinary approach is necessary to minimize negative interactions and unwanted adverse effects. In this review, we describe the patterns of organ crosstalk between the native and artificial organs, the incidence of AKI and need for RRT and associated mortality after extracorporeal organ support (ECOS) therapy, including the potential short- and long-term advantages and disadvantages of organ support in terms of renal function. We also review potential indications of RRT outside its conventional indications in patients with MODS, as well as technical considerations when RRT is used alongside other organ support therapies. Overall, available literature has not definitely established the ideal timing of these interventions, and whether early implementation impacts organ recovery and optimizes resource utilization is still a matter of open debate: it is possible that future research will be devoted to identify patient groups that may benefit from short- and long-term multiple organ support.

BackgroundPersistent congestion with deteriorating renal function is an important cause of adverse outcomes in heart failure. We aimed to characterize new approaches to evaluate renal congestion using Doppler ultrasonography.Methods and ResultsWe enrolled 205 patients with suspected or prediagnosed pulmonary hypertension (PH) undergoing right heart catheterization. Patients underwent renal Doppler ultrasonography and assessment of invasive cardiopulmonary hemodynamics, echocardiography, renal function, intra‐abdominal pressure, and neurohormones and hydration status. Four spectral Doppler intrarenal venous flow patterns and a novel renal venous stasis index (RVSI) were defined. We evaluated PH‐related morbidity using the Cox proportional hazards model for the composite end point of PH progression (hospitalization for worsening PH, lung transplantation, or PH‐specific therapy escalation) and all‐cause mortality for 1‐year after discharge. The prognostic utility of RVSI and intrarenal venous flow patterns was compared using receiver operating characteristic curves. RVSI increased in a graded fashion across increasing severity of intrarenal venous flow patterns (P<0.0001) and was significantly associated with right heart and renal function, intra‐abdominal pressure, and neurohormonal and hydration status. During follow‐up, the morbidity/mortality end point occurred in 91 patients and was independently predicted by RVSI (RVSI in the third tertile versus referent: hazard ratio: 4.72 [95% CI, 2.10–10.59; P<0.0001]). Receiver operating characteristic curves suggested superiority of RVSI to individual intrarenal venous flow patterns in predicting outcome (areas under the curve: 0.789 and 0.761, respectively; P=0.038).ConclusionsWe propose RVSI as a conceptually new and integrative Doppler index of renal congestion. RVSI provides additional prognostic information to stratify PH for the propensity to develop right heart failure.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT03039959.