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.

PURPOSE: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus. METHODS: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived experience (PWLE) were assembled. We focused on four main areas: (1) patient enrichment strategies, (2) prevention and attenuation studies, (3) treatment studies, and (4) innovative trial designs of studies other than traditional (parallel arm or cluster) randomized controlled trials. Using a modified Delphi process, recommendations and consensus statements were developed based on existing data, with > 90% agreement among panel members required for final adoption. RESULTS: The panel developed 12 consensus statements for clinical trial endpoints, application of enrichment strategies where appropriate, and inclusion of PWLE to inform trial designs. Innovative trial designs were also considered. CONCLUSION: The current lack of specific therapy for prevention or treatment of AKI demands refinement of future clinical trial design. Here we report the consensus findings of the 31st ADQI group meeting which has attempted to address these issues including the use of predictive and prognostic enrichment strategies to enable appropriate patient selection.

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.

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.