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Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study

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  • Nicholas A Maksimowski
  • James W Scholey
  • Vanessa R Williams
  • Nephrotic Syndrome Study Network (NEPTUNE)

Abstract

Background: Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of experimental kidney disease. ACE2 is on the X chromosome, and in mice, deletion of ACE2 leads to the development of focal segmental glomerulosclerosis (FSGS). The relationship between sex and renal ACE2 expression in humans with kidney disease is a gap in current knowledge. Methods: We studied renal tubulointerstitial microarray data and clinical variables from subjects with FSGS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) study. We compared relationships between ACE2 expression and age, estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), interstitial fibrosis, tubular atrophy, and genes implicated in inflammation and fibrosis in male and female subjects. Results: ACE2 mRNA expression was lower in the tubulointerstitium of males compared to females (P = 0.0026). Multiple linear regression analysis showed that ACE2 expression was related to sex and eGFR but not to age or treatment with renin angiotensin system blockade. ACE2 expression is also related to interstitial fibrosis, and tubular atrophy, in males but not in females. Genes involved in inflammation (CCL2 and TNF) correlated with ACE2 expression in males (TNF: r = -0.65, P

Suggested Citation

  • Nicholas A Maksimowski & James W Scholey & Vanessa R Williams & Nephrotic Syndrome Study Network (NEPTUNE), 2021. "Sex and kidney ACE2 expression in primary focal segmental glomerulosclerosis: A NEPTUNE study," PLOS ONE, Public Library of Science, vol. 16(6), pages 1-19, June.
    • Handle: RePEc:plo:pone00:0252758
    DOI: 10.1371/journal.pone.0252758
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