Nephrotic Syndrome and Renin-angiotensin System: Pathophysiological Role and Therapeutic Potential

Idiopathic Nephrotic Syndrome (INS) is the most frequent etiology of glomerulopathy in pediatric patients and one of the most common causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in this population. In this review, we aimed to summarize evidence on the pathophysiological role and therapeutic potential of the Renin-Angiotensin System (RAS) molecules for the control of proteinuria and for delaying the onset of CKD in patients with INS. This is a narrative review in which the databases PubMed, Web of Science, and SciELO were searched for articles about INS and RAS. We selected articles that evaluated the pathophysiological role of RAS and the effects of the alternative RAS axis as a potential therapy for INS. Several studies using rodent models of nephropathies showed that the treatment with activators of the Angiotensin-Converting Enzyme 2 (ACE2) and with Mas receptor agonists reduces proteinuria and improves kidney tissue damage. Another recent paper showed that the reduction of urinary ACE2 levels in children with INS correlates with proteinuria and higher concentrations of inflammatory cytokines, although data with pediatric patients are still limited. The molecules of the alternative RAS axis comprise a wide spectrum, not yet fully explored, of potential pharmacological targets for kidney diseases. The effects of ACE2 activators and receptor Mas agonists show promising results that can be useful for nephropathies including INS.

Automated summary

This review summarizes the evidence on the pathophysiological role and therapeutic potential of the Renin-Angiotensin System (RAS) molecules for the control of proteinuria and delaying the onset of chronic kidney disease (CKD) in patients with Idiopathic Nephrotic Syndrome (INS). Studies using rodent models showed that ACE2 activators and receptor Mas agonists can reduce proteinuria and improve kidney tissue damage. Limited data with pediatric patients also suggest that decreased urinary ACE2 levels correlate with proteinuria and higher concentrations of inflammatory cytokines in children with INS. The molecules of the alternative RAS axis have potential pharmacological targets for the treatment of kidney diseases including INS.