Use of an extended KDIGO definition to diagnose acute kidney injury in patients with COVID-19: A multinational study of the ISARIC cohort

Abstract Background Acute kidney injury (AKI) is one of the most common and significant problems in patients with COVID-19. However, little is known about the incidence and impact of AKI occurring in the community or early in the hospital admission. The traditional KDIGO definition can fail to identify patients for whom hospitalization coincides with recovery of AKI as manifested by a decrease in serum creatinine (sCr). We hypothesized that an extended KDIGO definition, adapted from the International Society of Nephrology 0by25 studies, would identify more cases of AKI in patients with COVID-19 and that these may correspond to community-acquired AKI with similarly poor outcomes as previously reported in this population. Methods and Findings All individuals in the ISARIC cohort admitted to hospital with SARS-CoV-2 infection from February 15 th , 2020, to February 1 st , 2021, were included in the study. Data was collected and analysed for the duration of a patient’s admission. Incidence, staging and timing of AKI were evaluated using a traditional and extended KDIGO (eKDIGO) definition which incorporated a commensurate decrease in serum creatinine. Patients within eKDIGO diagnosed with AKI by a decrease in sCr were labelled as deKDIGO. Clinical characteristic and outcomes – intensive care unit (ICU) admission, invasive mechanical ventilation and in-hospital death - were compared for all three groups of patients. The relationship between eKDIGO AKI and in-hospital death was assessed using survival curves and logistic regression, adjusting for disease severity and AKI susceptibility. 75,670 patients from 54 countries were included in the final analysis cohort. Median length of admission was 12 days (IQR 7, 20). There were twice as many patients with AKI identified by eKDIGO than KDIGO (31.7 vs 16.8%). Those in the eKDIGO group had a greater proportion of stage 1 AKI (58% vs 36% in KDIGO patients). Peak AKI occurred early in the admission more frequently among eKDIGO than KDIGO patients. Compared to those without AKI, patients in the eKDIGO group had worse renal function on admission, more in-hospital complications, higher rates of ICU admission (54% vs 23%) invasive ventilation (45% vs 15%) and increased mortality (38% vs 19%). Patients in the eKDIGO group had a higher risk of in-hospital death than those without AKI (adjusted OR: 1.78, 95% confidence interval: 1.71-1.8, p-value < 0.001). Mortality and rate of ICU admission were lower among deKDIGO than KDIGO patients (25% vs 50% death and 35% vs 70% ICU admission) but significantly higher when compared to patients with no AKI (25% vs 19% death and 35% vs 23% ICU admission) (all p values < 5×10 −5 ). Limitations include ad hoc sCr sampling, exclusion of patients with less than two sCr measurements, and limited availability of sCr measurements prior to initiation of acute dialysis. Conclusions The use of an extended KDIGO definition to diagnose AKI in this population resulted in a significantly higher incidence rate compared to traditional KDIGO criteria. These additional cases of AKI appear to be occurring in the community or early in the hospital admission and are associated with worse outcomes than those without AKI. Author Summary Why was this study done? Previous studies have shown that acute kidney injury (AKI) is a common problem among hospitalized patients with COVID-19. The current biochemical criteria used to diagnose AKI may be insufficient to capture AKI that develops in the community and is recovering by the time a patient presents to hospital. The use of an extended definition, that can identify AKI both during its development and recovery phase, may allow us to identify more patients with AKI. These patients may benefit from early management strategies to improve long term outcomes. What did the researchers do and find? In this study, we examined AKI incidence, severity and outcomes among a large international cohort of patients with COVID-19 using both a traditional and extended definition of AKI. We found that using the extended definition identified almost twice as many cases of AKI than the traditional definition (31.7 vs 16.8%). These additional cases of AKI were generally less severe and occurred earlier in the hospital admission. Nevertheless, they were associated with worse outcomes, including ICU admission and in-hospital death (adjusted odds ratio: 1.78, 95% confidence interval: 1.71-1.8, p-value < 0.001) than those with no AKI. What do these findings mean? The current definition of AKI fails to identify a large group of patients with AKI that appears to develop in the community or early in the hospital admission. Given the finding that these cases of AKI are associated with worse admission outcomes than those without AKI, identifying and managing them in a timely manner is enormously important.

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