Caution on Kidney Dysfunctions of COVID-19 Patients

  1. Zhen Li
  2. Ming Wu
  3. Jiwei Yao
  4. Jie Guo
  5. Xiang Liao
  6. Siji Song
  7. Jiali Li
  8. Guangjie Duan
  9. Yuanxiu Zhou
  10. Xiaojun Wu
  11. Zhansong Zhou
  12. Taojiao Wang
  13. Ming Hu
  14. Xianxiang Chen
  15. Yu Fu
  16. Chong Lei
  17. Hailong Dong
  18. Chuou Xu
  19. Yahua Hu
  20. Min Han
  21. Yi Zhou
  22. Hongbo Jia
  23. Xiaowei Chen
  24. Junan Yan

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Abstract

Background

To date, large amounts of epidemiological and case study data have been available for the Coronavirus Disease 2019 (COVID-19), which suggested that the mortality was related to not just respiratory complications. Here, we specifically analyzed kidney functions in COVID-19 patients and their relations to mortality.

Method

In this multi-centered, retrospective, observational study, we included 193 adult patients with laboratory-confirmed COVID-19 from 2 hospitals in Wuhan, 1 hospital in Huangshi (Hubei province, 83 km from Wuhan) and 1 hospital in Chongqing (754 km from Wuhan). Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected, including data regarding to kidney functions. Data were compared among three groups: non-severe COVID-19 patients (128), severe COVID-19 patients (65) and a control group of other pneumonia (28). For the data from computed tomographic (CT) scans, we also included a control group of healthy subjects (110 cases, without abnormalities in the lung and without kidney diseases). The primary outcome was a common presence of kidney dysfunctions in COVID-19 patients and the occurrence of acute kidney injury (AKI) in a fraction of COVID-19 patients. Secondary outcomes included a survival analysis of COVID-19 patients in conditions of AKI or comorbid chronic illnesses.

Findings

We included 193 COVID-19 patients (128 non-severe, 65 severe (including 32 non-survivors), between January 6 th and February 21 th ,2020; the final date of follow-up was March 4 th , 2020) and 28 patients of other pneumonia (15 of viral pneumonia, 13 of mycoplasma pneumonia) before the COVID-19 outbreak. On hospitaladmission, a remarkable fraction of patients had signs of kidney dysfunctions, including 59% with proteinuria, 44% with hematuria, 14% with increased levels of blood urea nitrogen, and 10% with increased levels of serum creatinine, although mild but worse than that in cases with other pneumonia. While these kidney dysfunctions might not be readily diagnosed as AKI at admission, over the progress during hospitalization they could be gradually worsened and diagnosed as AKI. A univariate Cox regression analysis showed that proteinuria, hematuria, and elevated levels of blood urea nitrogen, serum creatinine, uric acid as well as D-dimer were significantly associated with the death of COVID-19 patients respectively. Importantly, the Cox regression analysis also suggested that COVID-19 patients that developed AKI had a ∼5.3-times mortality risk of those without AKI, much higher than that of comorbid chronic illnesses (∼1.5 times risk of those without comorbid chronic illnesses).

Interpretation

To prevent fatality in such conditions, we suggested a high degree of caution in monitoring the kidney functions of severe COVID-19 patients regardless of the past disease history. In addition, upon day-by-day monitoring, clinicians should consider any potential interventions to protect kidney functions at the early stage of the disease and renal replacement therapies in severely ill patients, particularly for those with strong inflammatory reactions or a cytokine storm.

Funding

None.

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  1. ScreenIT

    SciScore for 10.1101/2020.02.08.20021212: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study has been approved by the Ethics Commissions of Wuhan Tongji Hospital (TJ-IRB20200216).
    Consent: Written informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious diseases.
    Randomizationnot detected.
    BlindingAn abdominalradiologist, who was blinded to the study grouping, transferred all original CT images to a dedicated computer for kidney texture analysis (Fire Voxel, New York University, NY, USA).
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line AuthenticationContamination: We also enrolled 28 patients diagnosed of other types of pneumonia (15 patients of viral pneumonia and 13 patients of mycoplasma pneumonia) before the COVID-19 outbreak from Wuhan Tongji Hospital as a control group.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The software of MATLAB (version 2018b, MathWorks) was used for statistical analysis.
    MATLAB
    suggested: (MATLAB, RRID:SCR_001622)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The limitations of our study and implications are as follows. First, clinical data regarding kidney functions were incomplete or absent in a substantial fraction of COVID-19 patients in the overburdened local medical system during the outbreak, thus we only included patients with complete data on kidney functions (except for CT data) in this study. The sampling bias was not subjective, because the existence and collection of our data was irrelevant to clinical considerations on whether COVID-19 patients had kidney diseases or not. In particular, kidney CT data were collected not from kidney-specific scans but from the abundant image volume of chest scans. Nevertheless, our results, though largely comparable with others, should not be interpreted in the standard framework of epidemiology. This is because all our included hospitals were designated to preferentially treat severe COVID-19 patients while most non-severe patients were treated in temporarily-built field hospitals during the outbreak.Second, various drugs and interventions had been applied to COVID-19 patients, the use of which could have side-effects on kidney functions during the course of treatment, e.g., invasive mechanical ventilation25. However, regardless of what could have damaged the kidney and caused AKI in COVID-19 patients, our suggestions on exercising a high caution in monitoring kidney functions still stood. Third, this is a retrospective study that does not provide sufficient data regarding the effect...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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  2. Version published to 10.1101/2020.02.08.20021212v2 on medRxiv
  3. Version published to 10.1101/2020.02.08.20021212v1 on medRxiv