Study Selection
A total of 2364 potentially relevant citations were identified and screened from variable databases. Firstly, 466 repeated studies were rejected in our research. Then the majority was sifted out based on titles or abstracts. There were 125 articles retrieved for detailed evaluation. Finally, 11 studies (6, 9-18) with 8815 patients with COVID-19 fulfilled eligibility criteria (Fig 1).
Study Characteristics
Table 1 presents the summary characteristics of the 11 included studies [6, 9-18]. The prevalence of AKI ranged from 10.3% to 81%. Ten studies [6,9-14, 16-18] were single center, and one[15] was multicenter. Eight studies [6, 9-13, 15, 17] used retrospective cohorts, two [14, 18] were observational studies, and one [16] was a cohort trial. Studies were conducted in China [9, 10,13, 15], United States [6, 11, 17, 18], France[12, 16], and Australia [14]. We assessed the risk of bias of the studies included in the qualitative review based on Newcastle-Ottawa Scale criteria.
Risk Factor Analysis
Male
All included studies provided eligible data for demonstrating the relationship between gender and AKI. The pooled results showed that males had a higher risk of developing AKI than females in patients with COVID-19 (OR=1.62, 95% CI, 1.24-2.13, P<0.05) (Fig S1). There was significant heterogeneity among these studies (I2=68%).
Race
Race was categorized into of the four groups: White, Black, Hispanic and Asian. The data for White and Black were available in four studies. Patients in White with COVID-19 had a significant increase in risk for AKI (OR=1.14, 95%CI, 1.03-1.26, p<0.05), whereas the pooled OR revealed a non-significant increase in Black (OR=1.29, 95%CI, 0.96-1.74, P=0.09). There studies reported the relationship between Hispanic and the risk of AKI. The results showed decreased risk of AKI in Hispanic patients with COVID-19, but the result was not statistically significant (OR=1.09, 95%CI, 0.46-1.046, P=0.08). Two papers reported information on Asian. The overall effect size was OR=1.18(95% CI, 0.75-1.12), p=0.39, with I2=0%, P=0.05(Fig S2).
Mechanical Ventilation
We identified six studies that reported available data on mechanical ventilation as risk factor for AKI. Meta-analysis of the six studies showed increased risk of AKI with mechanical ventilation use (OR=9.44, 95% CI, 5.16-17.27, p<0.05) (Fig 2). There was significant heterogeneity among these studies (I2=98%).
ICU admission
There studies with 7026 patients about ICU admission were pooled in the analysis (Fig 3). No heterogeneity across studies was detected (I2=0%, p=0.84), so fixed-effect model was applied. Patients in ICU had a strong significant increase in risk for AKI (OR=10.57, 95%CI, 9.33-11.98, p<0.00001).
Renin-Angiotensin-Aldosterone System (RAAS) inhibitors
Five studies that included a total of patients provided available data on the association between RAAS inhibitors use and AKI. Heterogeneity across studies was detected (I2=70%, p=0.009), so random-effect model was applied. However, no significant difference was found between the combined estimates (OR=1.17, 95%CI, 0.77-1.80, p=0.46) (Fig S3).
Vasopressor
Seven studies with 8205 patients contributed to pooled outcome. Heterogeneity across studies was detected (I2=93%, p<0.00001), so random-effect model was applied. The use of vasopressor was associated with the risk of AKI (OR=19.36, 95%CI, 16.77-22.34, p<0.00001) (Fig S4).
Glucocorticoids
There studies provided extractable data to analyze the association between the risk of AKI and glucocorticoids use. Heterogeneity across studies was detected (I2=80%, p=0.007), so random-effect model was applied. However, no significant difference was found between the combined estimates (OR=1.64, 95%CI, 0.27-9.91, p=0.59) (Fig S5).
Comorbidity
Comorbidities related to AKI were analyzed, including obesity, hypertension, diabetes mellitus, cardiac disease, chronic kidney disease (CKD), cerebrovascular disease, chronic obstructive pulmonary disease (COPD) and malignancy, as showed in Table 2. Five included studies reported the impact of obesity on AKI in patients with COVID-19. The heterogeneity of these studies was detected, showing I2=43% (p=0.14), under fixed-effect model. The synthesized OR was 1.75 (95%CI, 1.58-1.95, p<0.00001). Ten studies that explored the relationship between diabetes and AKI in patients with COVID-19 were included in the meta-analysis. The pooled data under fixed-effect model showed an OR of 1.73 (95% CI, 1.57-1.90, p<0.00001), with mild heterogeneity (I2=17%, p=0.25). Data on COVID-19 patients with hypertension were available from 9 studies with a pooled OR of 1.53 (95% CI, 1.04-2.20, p=0.03) from the random-fixed model with I2=83% (p<0.00001). Cardiac disease was regarded as a risk factor associated with AKI in patients with COVID-19, based on ten included studies. Analysis was conducted by fixed-model (I2=46%, p=0.05), with an OR of 1.71 (95% CI, 1.51-1.94, p<0.00001). Investigators in eight studies reported on relationships between CKD and AKI among patients with COVID-19. With an OR of 2.86 (95%CI, 1.54-5.32, p=0.0009), the history of CKD showed a significant trend towards higher AKI risk, under random-effect model (I2=79%, p<0.0001). Four studies were pooled to investigate the effect of cerebrovascular disease on AKI, revealing no statistical significance (OR=1.11, 95%CI, 0.47-2.65, p=0.06, random-effect model). Significant heterogeneity was found, with I2=59% (p=0.06). Six studies provided estimates for the relationship of between COPD and the incidence of AKI in patients with COVID-19, showing obvious statistical significance, with OR of 1.7 (95% CI, 1.40-2.07, p<0.00001) under fixed-effect model. Between-study heterogeneity was not apparent (I2=9%, p=0.36). Malignancy was not significantly associated with AKI in patients with COVID-19 (pooled OR=1.18, 95%CI, 0.97-1.45, p=0.85, under random-effect model), based on 5 studies. These studies showed a significant heterogeneity, with I2=66% and p=0.93.
Publication Bias
Publication bias assessments were carried out on studies that examined male sex. The funnel plot suggested possible publication bias in studies reporting male and risk of AKI, as asymmetric graph was observed. (Fig S6)