Mortality rate of acute kidney injury in SARS, MERS, and COVID-19 infection: a systematic review and meta-analysis

Acute kidney injury (AKI), a predictor for poor clinical outcomes, has been reported as a severe complication of different coronavirus infections, including novel coronavirus disease 2019 (COVID-19) [1]. COVID-19 is considered more contagious than previous coronavirus infections, e.g., severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) [2], but comparisons of mortality rates from AKI among these three coronavirus infections remain uninvestigated. We therefore conducted a systematic review and meta-analysis comparing the mortality rate in patients with SARS, MERS, and COVID-19 who developed AKI.

A systematic search of PUBMED and EMBASE from inception to June 5, 2020, included the keywords “coronavirus”, “COVID-19”, “MERS”, “SARS”, “acute kidney injury”, “prognosis”, and “mortality” with suitable MeSH terms to identify observational studies of relevance, e.g., case reports, case series, cross-sectional studies, and cohort studies. Reference lists of included, published, systematic reviews identified in the search were screened for additional studies. We excluded conference abstracts, review articles, or studies without reports of AKI mortality. Two reviewers (YTC, SCS) screened titles and abstracts of search results for relevance and individually and independently assessed the full texts of selected results. The final list of included studies was derived by discussion and unanimous agreement from both authors. Statistical analyses were performed using MedCalc for Windows, version 15.0 (MedCalc Software, Ostend, Belgium). We report the mortality rate from AKI in SARS, MERS, and COVID-19 infections as proportions with 95% confidence interval (CI) based on random effects model, represented by forest plot. We detected heterogeneity among studies using the Cochran Q test, with p value < 0.10 indicating significant heterogeneity, and calculated I² statistic to determine the proportion of total variation in study estimates attributable to heterogeneity.

After screening 97 records in total, we excluded 74 articles (15 duplicates, 11 irrelevant to study question, 1 conference abstract, 5 review articles and 42 lacking data on AKI mortality). Our final analysis included 23 articles comprising 4, 3 and 16 on SARS, MERS and COVID-19 infection, respectively. Demographic data for included articles are presented in Table 1. Overall, mortality in patients with SARS, MERS and COVID-19 infection, and developing AKI, was 77.4% (95%CI: 64.7–88.0). We found the mortality rate of AKI was highest in SARS (86.6%; 95%CI: 77.7–93.5), followed by COVID-19 (76.5%; 95%CI: 61.0–89.0) and MERS (68.5%; 95%CI: 53.8–81.5). There was no evidence of statistical heterogeneity among studies reporting AKI mortality in SARS (I2: 0.0%, p = 0.589) and MERS (I2: 0.0%, p =v0.758), but there was for COVID-19 infection (I2: 97.0%, p < 0.001) (Fig. 1).

The present analyses indicate AKI as a poor prognosis factor in coronavirus infections, whereby AKI mortality in COVID-19 is higher than MERS but lower than SARS infections. Possible mechanisms of higher AKI mortality following coronavirus infections are multifactorial (e.g., severe sepsis-related multi-organ failure, direct kidney involvement, and acute respiratory distress syndrome) [26‐28], although comparative pathogenesis of kidney involvement among the three infections remains unclear.

To our best knowledge, this is the first systematic review exploring AKI mortality of different coronavirus infections. However, we should be cautious about interpreting causal relationships between coronavirus infections and AKI, given the nature of observational data. Also, clinical heterogeneity between studies should be noted; for example, various healthcare systems of included studies may produce different AKI mortality rates. Coronaviruses are unlikely to be eliminated in the near future, and our synthesis indicates that AKI secondary to coronavirus infection may contribute to higher mortality. Hence, in the current exceptional pandemic, first-line healthcare providers should recognize the importance of timely detection of AKI and consider all available treatment options for maintenance of kidney functions to prevent death in COVID-19 patients [29].