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      Acute kidney injury following multisystem inflammatory syndrome associated with SARS-CoV-2 infection in children: a systematic review and meta-analysis

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          Abstract

          Introduction

          Multisystem inflammatory syndrome (MIS-C) is a rare paediatric hyper-inflammatory disorder that occurs following SARS-CoV-2 infection. Acute kidney injury (AKI) occurs in approximately one-quarter to one-third of the patients with MIS-C and is associated with poor prognosis in critically ill children. This systematic review is aimed to evaluate the incidence of AKI, mortality, and the need for kidney replacement therapy (KRT) in patients with MIS-C.

          Methods

          We searched databases from Medline, EMBASE, Cochrane Register, and Google Scholar from December 2019 to December 2021 with our search strategy. Studies meeting the following criteria were included in this systematic review: (1) articles on AKI in MIS-C; (2) studies providing AKI in MIS-C and COVID-19 infection separately; (3) studies reporting outcomes such as mortality, KRT, serum creatinine; length of hospital/ICU stay.

          Quality assessment

          The quality of the included studies was independently assessed by using the National Heart Lung and Blood Institute (NHLBI) quality assessment tool for cohort studies and case series.

          Statistical analysis

          Outcomes and their 95% confidence intervals (CI) were reported if a meta-analysis of these outcomes was conducted. Heterogeneity was reported using I 2 statistics, and heterogeneity ≥ 50% was considered high. We used Baujat’s plot for the contribution of each study toward overall heterogeneity. In sensitivity analysis, the summary estimates were assessed by repeating meta-analysis after omitting one study at a time. Forest plots were used for reporting outcomes in each study and with their 95% CI. All statistical tests were performed using R software version 4.0.3.

          Results

           A total of 24 studies were included in this systematic review and of these, 11 were included in the meta-analysis. The pooled proportion of patients with MIS-C developing AKI was 20% (95% CI: 14–28%, I 2 = 80%). Pooled proportion of death in children with MIS-C was 4% (95% CI: 1–14%; I 2 = 93%). The odds of death in patients with AKI were 4.68 times higher than in patients without AKI (95% CI: 1.06–20.7%; I 2 = 17%). The overall pooled proportion of MIS-C-induced AKI patients requiring KRT was 15% (95% CI: 4–42%; I 2 = 91%).

          Conclusion

          Approximately one-fifth of children with MIS-C develop AKI which is associated with higher odds of death.

          PROSPERO registration: CRD42022306170

          Graphical abstract

          A higher resolution version of the Graphical abstract is available as Supplementary information

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00467-022-05701-3.

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          Most cited references38

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          Measuring inconsistency in meta-analyses.

          Julian P T Higgins, Simon G Thompson, Jonathan J Deeks … (2003)
          Article 0 comments Cited 10836 times – based on 0 reviews     Review now
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            Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

            Leora Feldstein, Erica Rose, Steven M. Horwitz … (2020)
            Abstract Background Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. Methods We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. Results We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease–like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). Conclusions Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.)
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              Multisystem Inflammatory Syndrome in Children in New York State

              Elizabeth M Dufort, Emilia H. Koumans, Eric Chow … (2020)
              Abstract Background A multisystem inflammatory syndrome in children (MIS-C) is associated with coronavirus disease 2019. The New York State Department of Health (NYSDOH) established active, statewide surveillance to describe hospitalized patients with the syndrome. Methods Hospitals in New York State reported cases of Kawasaki’s disease, toxic shock syndrome, myocarditis, and potential MIS-C in hospitalized patients younger than 21 years of age and sent medical records to the NYSDOH. We carried out descriptive analyses that summarized the clinical presentation, complications, and outcomes of patients who met the NYSDOH case definition for MIS-C between March 1 and May 10, 2020. Results As of May 10, 2020, a total of 191 potential cases were reported to the NYSDOH. Of 95 patients with confirmed MIS-C (laboratory-confirmed acute or recent severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and 4 with suspected MIS-C (met clinical and epidemiologic criteria), 53 (54%) were male; 31 of 78 (40%) were black, and 31 of 85 (36%) were Hispanic. A total of 31 patients (31%) were 0 to 5 years of age, 42 (42%) were 6 to 12 years of age, and 26 (26%) were 13 to 20 years of age. All presented with subjective fever or chills; 97% had tachycardia, 80% had gastrointestinal symptoms, 60% had rash, 56% had conjunctival injection, and 27% had mucosal changes. Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 62% received vasopressor support, 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died. The median length of hospital stay was 6 days. Conclusions The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction.
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                Author and article information

                Contributors
                Girish Chandra Bhatt:
                ORCID: http://orcid.org/0000-0001-6504-6008
                drgcbhatt@gmail.com
                Journal
                Journal ID (nlm-ta): Pediatr Nephrol
                Journal ID (iso-abbrev): Pediatr Nephrol
                Title: Pediatric Nephrology (Berlin, Germany)
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 0931-041X
                ISSN (Electronic): 1432-198X
                Publication date (Electronic): 9 August 2022
                Pages: 1-14
                Affiliations
                [1 ]GRID grid.464753.7, ISNI 0000 0004 4660 3923, Department of Pediatrics, ISN-SRC, , All India Institute of Medical Sciences (AIIMS), ; Room no 1023, Academic Block, Saket Nagar, Bhopal, MP 462024 India
                [2 ]Advanced Pediatrics Centre, Division of Clinical Immunology and Rheumatology, Post Graduate Institute of Medical Sciences (PGI), Chandigarh, India
                [3 ]GRID grid.464753.7, ISNI 0000 0004 4660 3923, Department of Nephrology, , All India Institute of Medical Sciences (AIIMS), ; Bhopal, MP India
                Author information
                http://orcid.org/0000-0001-6504-6008
                Article
                Publisher ID: 5701
                DOI: 10.1007/s00467-022-05701-3
                PMC ID: 9362633
                PubMed ID: 35943577
                SO-VID: 54110492-c9b4-491f-8af3-c20bfd17ea2a
                Copyright © © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 24 April 2022
                Date revision received : 19 July 2022
                Date accepted : 20 July 2022
                Categories
                Subject: Systematic Review/Meta-analysis

                ScienceOpen disciplines: Nephrology
                Keywords: multisystem inflammatory syndrome in children (mis-c),acute kidney injury (aki),meta-analysis
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: multisystem inflammatory syndrome in children (mis-c), acute kidney injury (aki), meta-analysis

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