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

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.

Identification and characterization of alamandine-(1-5), a new component of the Renin-Angiotensin System with unique properties

“…The precise meaning of this finding is currently unknown and our sample size is limited. However, we might speculate that, as previously reported by other RAS components 39 , alamandine-(1-5) may have a role in the pathophysiology of primary nephrotic syndrome. These novel findings combined with the many effects of alamandine-(1-5) unmasked in our study, indicates that this pentapeptide may be involved in several actions of the RAS.…”

The Yin and Yang of ACE/ACE2 Pathways: The Rationale for the Use of Renin-Angiotensin System Inhibitors in COVID-19 Patients

“…Indeed, in chronic kidney disease patients without a history of cardiovascular disease, there was a significant decrease in circulating ACE2 activity and zinc levels when compared with healthy control subjects [96,97]. Since proteinuria was associated with lower blood levels of sACE2 protein [153] and chronic kidney disease patients had higher urinary zinc excretion than healthy controls [97], low sACE2 activity in chronic renal diseases and protection from SARS might derive from a higher sACE2 and/or Zn 2+ renal excretion. Indeed, sACE2 is detectable in urine of healthy subjects and urinary sACE2 protein levels are elevated in patients with chronic renal diseases and in hypertensive patients treated with the Ang II type 1 receptor blocker (ARB) olmesartan [41,154].…”

Proteinuria and Bilirubinuria as Potential Risk Indicators of Acute Kidney Injury during Running in Outpatient Settings

“…The pathophysiological mechanisms of proteinuria can be partially explained by increasing glomerular capillary permeability to proteins and reduced protein reabsorption capacity in the renal tubules. Still, exercise-induced proteinuria is not fully understood, but it seems that the renin-angiotensin system and prostaglandins have an essential role in its development [38].…”