RESUMO
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.
Assuntos
Síndrome Nefrótica/genética , Peptidil Dipeptidase A/genética , Proteinúria/genética , Sistema Renina-Angiotensina/genética , Adolescente , Angiotensina I/genética , Angiotensina I/urina , Angiotensina II/genética , Angiotensina II/urina , Enzima de Conversão de Angiotensina 2 , Animais , Estudos de Casos e Controles , Quimiocina CCL2/genética , Quimiocina CCL2/urina , Quimiocina CXCL10/genética , Quimiocina CXCL10/urina , Criança , Estudos Transversais , Feminino , Expressão Gênica , Humanos , Masculino , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/patologia , Síndrome Nefrótica/urina , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/urina , Peptidil Dipeptidase A/urina , Proteinúria/diagnóstico , Proteinúria/patologia , Proteinúria/urinaRESUMO
PURPOSE: Clinical- and histopathology-based scores are the limited predictors of allograft outcome. Thus, predictors of allograft survival still remain a challenge. This study aimed to evaluate the urinary levels of chemokines and anti-inflammatory molecules at 30, 90, and 300 days after renal transplantation and to further correlate these measurements to graft function. METHODS: Glomerular filtration rate (GFR) and urinary levels of MCP-1/CCL2, MIP-1α/CCL3, RANTES/CCL5, IL-8/CXCL8, IP-10/CXCL10, interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor-1, and receptor-2 were determined at 30, 90, and 300 days after renal transplantation in 22 patients. Transplanted patients were also divided according to the type of donor (living donor, LD, n = 13 or deceased donor, DD, n = 9). RESULTS: Urinary levels of all molecules, except MIP-1α/CCL3, remained unchanged at 30, 90, and 300 days after transplantation in our 22 patients. MIP-1α/CCL3 levels significantly reduced from 30 to 300 days and showed a negative correlation with GFR at 30 days. The comparison between LD and DD groups showed similar levels of all markers, except for MCP-1/CCL2, which presented higher values in LD than in DD at 30 days. sTNFR1 and MCP-1/CCL2 significantly reduced from 30 to 300 days in LD group, but only sTNFR2 concentrations at 30 days were negatively correlated with GFR at 300 days. On the other hand, in DD group, IL-1Ra concentrations at 30 and at 90 days were positively correlated with GFR at 300 days. CONCLUSION: Urinary chemokine and anti-inflammatory molecules measurements may be a promising tool in the follow-up of renal transplanted patients.