key: cord-0992216-4dkyvi6o authors: Noble, Rebecca A; Selby, Nicholas M title: The changing nature of COVID-19 associated AKI: Where are we now? date: 2021-11-18 journal: Nephrol Dial Transplant DOI: 10.1093/ndt/gfab326 sha: 86350a1562eacee5e8cece3d64b498da8cc0e073 doc_id: 992216 cord_uid: 4dkyvi6o nan Since the emergence of the Sars-CoV-2 (COVID-19) pandemic a huge amount of research and data collection has allowed better understanding of the epidemiology of the disease. Although the virus predominantly affects the respiratory system it is clear that other organ systems can also be affected, with acute kidney injury (AKI) one of the most common complications [1, 2] . Whilst specific forms of renal disease (e.g. collapsing glomerulopathies) have been described, the majority of cases reflect the effects of an acute systemic inflammatory illness on the kidney [3, 4] . Risk factors for developing COVID-19 associated AKI have been well-described and include gender, ethnicity, requirement for invasive ventilation and pre-existing long-term conditions, for example diabetes mellitus or chronic kidney disease (CKD) [5] . The presence of AKI is also strongly associated with increased short-term mortality [5] . One of the most striking observations is that the incidence of COVID-19 associated AKI has reduced over time, with progressively lower rates of kidney replacement place prior to the current pandemic, which was ready to respond to a major infectious disease outbreak. It was therefore possible to collect prospective data from the time of the first reported cases in the UK and do so at scale, involving 254 hospitals and assembling a cohort of 114,131 patients who met the inclusion criteria for this analysis. This study used data collected between January 17 th 2020 and December 5 th 2020, capturing the first and part of the second UK waves of the pandemic. As well as studying associations and outcomes of AKI, the analyses also sought to identify factors that were associated with changes in the rates of AKI over time. The study was not designed to report longer term outcomes or examine the rates of chronic kidney disease after AKI. Two groups were defined: i) patients who needed acute KRT (n=85,687); and ii) 'biochemical AKI' representing patients with AKI identified based on changes in serum creatinine (using the NHS AKI detection algorithm and the KDIGO AKI criteria) who did not receive KRT (n=41,294). In the latter group, the majority of AKI was stage 1 (65.9%) and 55% was present at time of admission to hospital. AKI even in its mildest form was associated with an increased mortality, 40% of all AKI patients died during the 28-day follow-up, and there was a step-wise increase in the risk of death with each increase in AKI stage. Confirming prior findings, risk factors for both AKI and KRT included obesity, pre-existing CKD, male gender, and black race, with those of Asian ethnicity also at increased risk in combination with co-morbidities, especially CKD. The study also described a clear fall in the rates of KRT and biochemical AKI over KRT in oxygen-requiring COVID-19 is more robust; the caveat is that the effects on biochemical AKI, which were not assessed in RECOVERY, are less certain. Considerations regarding remdesivir are slightly different, because current RCTs do not report renal outcomes. Additionally, the mode of action of remdesivir (a nucleoside analogue that targets viral replication) differs from dexamethasone (which targets systemic inflammation), and whilst there is evidence for both having an effect on overall patient outcomes, it shouldn't be assumed that both will necessarily benefit renal outcomes. Forthcoming data from RECOVERY may help, with the possibility of contrasting the effect of anti-inflammatory approaches (dexamethasone, tocilizumab) on requirement for KRT with those of anti-virals (monoclonal antibodies casirivimab and imdevimab against the coronavirus spike protein). At present however, there is no evidence that shows remdesivir has a significant impact on the incidence of AKI or requirement for KRT. The results of the study by Sullivan et al also posed some additional unanswered questions. It was notable that even after June 2020, there was a sizeable group of patients requiring oxygen who did not receive dexamethasone, despite this being recommended practice by that time. Reasons for this were unclear, but this may also play into the argument of unmeasured confounders. There was also a somewhat paradoxical observation that increased age was associated with a lower rate of AKI, which we can speculate may relate to differences in the threshold and primary reason for hospital admission across age groups. In summary, this impressively large, multicentre prospective study that was carried associated AKI and receipt of KRT, and once again highlights the significantly increased risk of short-term adverse outcomes that the presence of AKI incurs. The fall in the rates of AKI and KRT over time is gratifying, but AKI remains a common complication of COVID-19. AKI should therefore remain an important focus for practitioners caring for hospitalised patients with COVID-19, and until more data is available, we should continue to pay attention to all of the possible contributing factors that may have led to these improvements. COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis COVID-19-Associated Kidney Injury: A Case Series of Kidney Biopsy Findings Acute kidney injury associated with COVID-19: A retrospective cohort study Covid-19 and acute kidney injury in hospital: summary of NICE guidelines Dexamethasone in Hospitalized Patients with Covid-19 Acute kidney injury prevalence, progression and long-term outcomes in critically ill patients with COVID-19: a cohort study None declared.