Evidence for a role of angiotensin converting enzyme 2 in proteinuria of idiopathic nephrotic syndrome

Biosci Rep. 2019 Jan 3;39(1):BSR20181361. doi: 10.1042/BSR20181361. Print 2019 Jan 31.

Abstract

Introduction: Renin angiotensin system (RAS) plays a role in idiopathic nephrotic syndrome (INS). Most studies investigated only the classical RAS axis. Therefore, the aims of the present study were to evaluate urinary levels of RAS molecules related to classical and to counter-regulatory axes in pediatric patients with INS, to compare the measurements with levels in healthy controls and to search for associations with inflammatory molecules, proteinuria and disease treatment. Subjects and methods: This cross-sectional study included 31 patients with INS and 19 healthy controls, matched for age and sex. Patients and controls were submitted to urine collection for measurement of RAS molecules [Ang II, Ang-(1-7), ACE and ACE2] by enzyme immunoassay and cytokines by Cytometric Bead Array. Findings in INS patients were compared according to proteinuria: absent (<150 mg/dl, n = 15) and present (≥150 mg/dl, n = 16). Results: In comparison to controls, INS patients had increased Ang II, Ang-(1-7) and ACE, levels while ACE2 was reduced. INS patients with proteinuria had lower levels of ACE2 than those without proteinuria. ACE2 levels were negatively correlated with 24-h-proteinuria. Urinary concentrations of MCP-1/CCL2 were significantly higher in INS patients, positively correlated with Ang II and negatively with Ang-(1-7). ACE2 concentrations were negatively correlated with IP-10/CXCL-10 levels, which, in turn, were positively correlated with 24-h-proteinuria. Conclusion: INS patients exhibited changes in RAS molecules and in chemokines. Proteinuria was associated with low levels of ACE2 and high levels of inflammatory molecules.

Keywords: cytokines; nephrotic syndrome; proteinuria; renin-angiotensin system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Angiotensin I / genetics
  • Angiotensin I / urine
  • Angiotensin II / genetics
  • Angiotensin II / urine
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Case-Control Studies
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / urine
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / urine
  • Child
  • Cross-Sectional Studies
  • Female
  • Gene Expression
  • Humans
  • Male
  • Nephrotic Syndrome / diagnosis
  • Nephrotic Syndrome / genetics*
  • Nephrotic Syndrome / pathology
  • Nephrotic Syndrome / urine
  • Peptide Fragments / genetics
  • Peptide Fragments / urine
  • Peptidyl-Dipeptidase A / genetics*
  • Peptidyl-Dipeptidase A / urine
  • Proteinuria / diagnosis
  • Proteinuria / genetics*
  • Proteinuria / pathology
  • Proteinuria / urine
  • Renin-Angiotensin System / genetics*

Substances

  • CCL2 protein, human
  • CXCL10 protein, human
  • Chemokine CCL2
  • Chemokine CXCL10
  • Peptide Fragments
  • Angiotensin II
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)

Supplementary concepts

  • Nephrosis, congenital