Abstract

PurposeNephrotic syndrome is a common chronic illness encountered during childhood. Infections have been identified as a cause of nephrotic syndrome. The aim of this study was to evaluate the association between enteroviral infection and nephrotic syndrome.MethodsA nationwide retrospective cohort study was conducted by analyzing data from the National Health Insurance Research Database in Taiwan. Children aged <18 years with enteroviral infection were enrolled. Non-enterovirus-infected children were randomly selected as the comparison cohort. The primary endpoint was the occurrence of nephrotic syndrome.MethodsThis study included 280,087 enterovirus-infected children and 280,085 non-enterovirus-infected children. The mean age of the enterovirus-infected children was 2.38 years, and 53.7% of these children were boys. The overall incidence densities of nephrotic syndrome for enterovirus- and non-enterovirus-infected children were 2.65 and 2.21 per 10,000 person-years, respectively. The enterovirus-infected cohort had a higher cumulative incidence of nephrotic syndrome than did the non-enterovirus-infected cohort (log-rank test, p = 0.01). Multivariable analyses revealed that children with enteroviral infection were significantly associated with an increased risk of nephrotic syndrome compared with those without enteroviral infection (adjusted hazard ratio, 1.20; 95% confidence interval, 1.04–1.39; p = 0.01), particularly in children infected with coxsackievirus. Subgroup analyses revealed that enterovirus-infected girls, children of blue-collar workers, and children without allergies had a higher risk of nephrotic syndrome than did children in the non-enterovirus-infected cohort.ConclusionThis study revealed a significant association between enteroviral infection and nephrotic syndrome. Additional studies elucidating the role and pathogenesis of enterovirus in nephrotic syndrome are warranted.

Highlights

  • Nephrotic syndrome, characterized by proteinuria, hypoalbuminemia, and generalized edema, is among the most common chronic kidney diseases encountered during childhood [1,2]

  • Multivariable analyses revealed that children with enteroviral infection were significantly associated with an increased risk of nephrotic syndrome compared with those without enteroviral infection, PLOS ONE | DOI:10.1371/journal.pone

  • This study revealed a significant association between enteroviral infection and nephrotic syndrome

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Summary

Introduction

Nephrotic syndrome, characterized by proteinuria, hypoalbuminemia, and generalized edema, is among the most common chronic kidney diseases encountered during childhood [1,2]. It can be idiopathic or provoked by systemic diseases (eg, diabetes mellitus, systemic lupus erythematosus, amyloidosis, and cancers), drugs, and infections [2]. Enteroviruses include diverse RNA viruses classified in the Picornaviridae family. Enteroviral infections are common among children worldwide. The Centers for Disease Control and Prevention estimated that approximately 10–15 million infections of non-polio enteroviruses occurred in the United States annually [7]. Enteroviral infections present a wide range of manifestations, such as hand-foot-andmouth disease, meningitis, encephalitis, conjunctivitis, herpangina, myocarditis, pericarditis, acute flaccid paralysis, and inflammatory muscle disease [5,6,7]

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