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Association of GSTM1 Deletion With Progression of CKD in Children: Findings From the Chronic Kidney Disease in Children (CKiD) Study

  1. Author:
    Levy, Rebecca V
    Reidy, Kimberly J
    Le, Thu H
    David,Victor
    Winkler,Cheryl
    Xu, Yunwen
    Warady, Bradley
    Furth, Susan
    Kaskel, Frederick
    Melamed, Michal L

  2. Author Address

    Department of Medicine, Division of Nephrology, University of Rochester School of Medicine and Dentistry. Electronic address: rebecca_levy@urmc.rochester.edu., Department of Pediatrics, Division of Pediatric Nephrology, Montefiore Medical Center, Bronx, NY, United States., Basic Science Laboratory, Center for Cancer Research, Frederick National Laboratory, Frederick, MD, USA., Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA., Department of Pediatrics, Division of Pediatric Nephrology, Children 39;s Mercy Kansas City MO, USA., Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania and the Children 39;s Hospital of Philadelphia, Philadelphia, PA, USA., Department of Medicine, Division of Nephrology, Albert Einstein College of Medicine, Bronx, NY, United States.,
    1. Year: 2021
    2. Date: Dec 03
  2. Journal: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
  4. Type of Article: Article
  1. Abstract:

    Loss of function of the product of the GSTM1 gene has been implicated in rapid progression of adult CKD. Its role in pediatric CKD has not been previously described. The study is a secondary analysis of a prospective observational cohort examining the association between deletions in GSTM1 and progression of CKD. We used data and samples from the prospective Chronic Kidney Disease in Children (CKiD) cohort aged 1-16 years at enrollment with CKD. We defined exposure fewer than two GSTM1 alleles on real-time polymerase chain reaction amplification. The primary outcome was a composite of 50% decrease in estimated glomerular filtration rate (eGFR) or start of kidney replacement therapy. Secondary outcomes included remission of proteinuria in children with glomerular disease and cardiovascular complications. The primary analysis was by Cox proportional hazards model. Analysis was adjusted for age, sex, race, ethnicity, BMI category, diagnosis category, and eGFR. 674 children were included in the analysis. Mean age at most recent visit was 11.9 years; 61% were male and 20% were Black. There were 241 occurrences of the primary outcome at the time of analysis. After adjustment for baseline characteristics, the risk of progression of CKD for exposed children was 1.94 (1.27, 2.97). The effect size was similar with either one or two deletions (autosomal dominant inheritance). The relationships between number of functional GSTM1 alleles and prespecified secondary outcomes were not statistically significant after adjustment. Missing data, especially for secondary outcomes, and relatively small sample size compared to genetic studies in adults. GSTM1 deletion is associated with more rapid progression of pediatric CKD after adjustment in this large prospective cohort. No statistically significant associations were seen with secondary outcomes. If replicated, these findings may inform development of interventions for CKD in children. Copyright © 2021. Published by Elsevier Inc.

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External Sources

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  2. DOI: 10.1053/j.ajkd.2021.10.007
  3. PMID: 34871703
  4. PII : S0272-6386(21)01009-X

Library Notes

  1. Fiscal Year: FY2021-2022
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