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Kidney ACE2 expression: Implications for chronic kidney disease.

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Area of Science:

  • Nephrology
  • Virology
  • Genomics

Background:

  • Angiotensin-converting enzyme 2 (ACE2) and Transmembrane protease, serine 2 (TMPRSS2) are key in SARS-CoV-2 infection.
  • Chronic kidney disease (CKD) and demographic factors influence COVID-19 severity.
  • The relationship between kidney expression of ACE2/TMPRSS2 and clinical variables in CKD is not well understood.

Purpose of the Study:

  • To investigate the expression of ACE2 and TMPRSS2 in the kidneys of healthy living donors (HLD) and CKD patients.
  • To determine the association between kidney ACE2/TMPRSS2 expression and clinical variables like sex, age, BMI, and estimated glomerular filtration rate (eGFR).
  • To explore the correlation between ACE2/TMPRSS2 expression and genes involved in inflammation and fibrosis.

Main Methods:

  • Microarray analysis of renal tubulointerstitial and glomerular expression data from HLD and CKD patients.
  • Collection and analysis of clinical variables including sex, age, BMI, and eGFR.
  • Statistical analysis to assess correlations between gene expression and clinical parameters.

Main Results:

  • ACE2 expression was similar in tubulointerstitium but lower in glomeruli of CKD patients vs. HLD.
  • ACE2 expression was higher in females than males in both HLD and CKD groups.
  • Tubulointerstitial ACE2 expression in CKD correlated with eGFR and age, and inversely with inflammation/fibrosis genes.

Conclusions:

  • Kidney expression of ACE2 and TMPRSS2 varies between HLD and CKD patients.
  • ACE2 expression in the kidney is influenced by sex, eGFR, and is linked to inflammation and fibrosis pathways.
  • These findings highlight potential mechanisms linking kidney disease, viral entry, and disease severity.