Is creatinine an independent risk factor for predicting adverse outcomes in COVID-19 patients?

To the Editor,

Recently, a meta‐analysis by Zheng et al reported that increased creatinine (Cr) was significantly associated with critical or mortal outcomes in coronavirus disease 2019 (COVID‐19) patients based on unadjusted effect estimates (odds ratio (OR): 5.19, 95% confidence interval (CI): 2.19‐12.83). To our knowledge, in a univariate model, the adverse outcomes of COVID‐19 patients are significantly associated with Cr, , , , while the significant association disappeared in a multivariate model. Several confounders (age, gender and co‐existing comorbidities) might affect the association of creatinine with adverse outcomes in COVID‐19 patients. Therefore, a quantitative meta‐analysis based on adjusted effect estimates was performed to clarify the association of Cr value with adverse outcomes in COVID‐19 patients.

All the related articles were searched from PubMed, Web of Science and EMBASE on 23 July 2020 by using the following key‐words: “creatinine or laboratory”, “2019‐nCoV or SARS‐CoV‐2 or novel coronavirus 2019 or COVID‐19 or coronavirus disease 2019” and “adverse outcome or severe or critical or severity or mortality or fatality or death”.

The meta‐analysis was processed by using Stata14.2. I2 statistics was used to assess heterogeneity. The value of I2 > 50% indicated evident heterogeneity across articles and a random‐effects model was selected; otherwise a fixed‐effects model was used. Meta‐regression and sensitivity analysis were conducted to assess the source of heterogeneity and evaluate the robustness of our findings respectively. Begg's test and Egger's test were used in the assessment of publication bias.

Fifteen articles with 7,420 patients were included in this meta‐analysis. The main characteristics are shown in Table S1. Our results showed that increased Cr values were significantly associated with adverse COVID‐19 patients (pooled effect: 1.10, 95% CI: 1.04‐1.16, P < .001, random‐effects model) (Figure 1A). Meta‐regression demonstrated that hypertension might be a source of heterogeneity (P = .037). Heterogeneity among studies adjusted for hypertension was significantly lower (I2 = 11.3%, P = .343, pooled effect = 1.03, 95% CI = 1.01‐1.05) (Figure 1B). The results of sensitivity analysis demonstrated the pooled effect was robust by excluding each study successively (Figure 1C). Publication bias was not presented in Begg's test (P = .381), but presented in the Egger's test (P = .002).

Figure 1

Forest plot of the pooled effect (A) and Subgroup analysis based on whether hypertension was included as an adjustment factor (1, yes; 0, no) of the enrolled studies (B); Sensitivity analysis (C)

This study has some limitations. First, although this meta‐analysis was based on adjusted effect estimates, the adjusted factors were different among studies. Second, we tried to screen eligible studies through three databases but the publication bias still existed in Egger's test. Third, most of the included articles are retrospective, and only two are prospective, so we did not perform subgroup analysis by study design.

In conclusion, increased Cr value was an independent risk factor for predicting adverse outcomes in COVID‐19 patients. Further study based on prospective data with larger sample size is required to confirm the conclusion of our meta‐analysis.

CONFLICTS OF INTEREST

All authors report that they have no potential conflicts of interest.

AUTHORS CONTRIBUTION

W. Y. D. and Y. H. Y. designed the analysis; W. J. and Z. P. H. extracted the data; W. J. performed the analysis; W. J. and S. L. contributed to the statistical analyses and interpretation; W. J. drafted the manuscript, which was modified by W. Y. D. and Y. H. Y. All authors read and approved the final manuscript.

Funding information

This study was supported by a grant from the National Natural Science Foundation of China (No. 81973105).

Table S1

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