Incidence of acute kidney injury in COVID-19 infection: a systematic review and meta-analysis

Coronavirus disease 2019 (COVID-19), primarily affecting respiratory systems, has become pandemic and spread worldwide. Acute kidney injury (AKI) has been reported as a severe complication of COVID-19 with a higher risk of mortality [1], but the incidence of AKI among those infected with COVID-19 is currently only based on reports from small case series and retrospective studies [2, 3]. Therefore, in this work, we aim to perform a systematic review and meta-analysis of published articles to quantify the incidence of AKI in COVID-19 patients.

We performed a systematic search via PUBMED and EMBASE using the keywords “COVID-19” and “acute kidney injury” to identify relevant observational studies, such as case series and cohort studies published between 2019 and May 11, 2020. We also manually examined the reference lists of included studies and reviewed the AKI reports in epidemiological features and clinical courses of COVID-19 patients in high-profile general medicine journals (e.g., BMJ, JAMA, Lancet, and NEJM). Two independent reviewers (YTC and SCS) assessed articles, including title, abstract, and full text to determine whether studies were eligible for inclusion. In cases of divergences, results were discussed with a third reviewer (YCC). All statistical analyses were performed using MedCalc for Windows, version 15.0 (MedCalc Software, Ostend, Belgium). The incidence of AKI is expressed as proportion and 95% confidence interval (CI) using the random effects model and presented as a forest plot. We used the Cochran Q test to detect heterogeneity among studies, with a p value < 0.10 indicating significant heterogeneity. We calculated I² statistic to measure the proportion of total variation in study estimates attributed to heterogeneity.

Of 65 articles screened, we excluded 45: 7 studies were duplicates, 8 studies were irrelevant, 9 studies failed to report the number of patients in the study cohort, and 21 studies did not report AKI data. Our final analysis included 20 articles comprising 6945 patients from China, Italy, the UK, and the USA. Demographic data for the included articles are summarized in Table 1. Notably, most of the studies (80%) were reported from China. We found the incidence of AKI was 8.9% (95% CI 4.6–14.5) in COVID-19 patients, but there was evidence of statistical heterogeneity among the studies with I² = 97.8% and p < 0.001 (Fig. 1).

Previous studies reported the incidence of AKI largely from small case series or cohorts of COVID-19 patients, but our findings indicated that nearly 9 out of 100 developed AKI among a total of 6945 COVID-19 patients. This was close to the incidence rate of AKI in patients with community-acquired pneumonia [24].

Several mechanisms are possible for AKI in COVID-19 patients, including multi-organ dysfunction syndrome, SARS-CoV-2 direct kidney infection [25], AKI following acute respiratory distress syndrome (ARDS), infection-related generalized mitochondrial failure, and cytokine storm syndrome. Early recognition and treatment of AKI may limit associated complications such as long-term chronic kidney disease or end-stage kidney disease [26].

This study has several limitations. First, since the majority of included studies came from China and the USA, the generalizability of our findings into other countries may be limited. Second, clinical heterogeneity between studies should be noted, whereby detailed information on patient characteristics was lacking in the published articles. For example, two studies included patients post kidney transplantation, and the reported incidences of AKI were higher than in other studies which lacked information on how many patients had had kidney transplantation. With the disease burden of COVID-19 still increasing every day, we hope our synthesis can raise clinical awareness, early recognition, and intervention for AKI in patients hospitalized with COVID-19 for first-line healthcare providers.