RESUMEN
The pathogenesis of idiopathic nephrotic syndrome (INS) remains unknown. Several findings suggest a role for the immune system. This study aimed to evaluate immune mediators in INS by measuring plasma and urinary levels of transforming growth factor beta1 (TGF-beta1), monocyte chemoattractant protein-1 (MCP-1/CCL2), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and IL-8 (IL-8/CXCL8) in pediatric patients with INS and in age-matched healthy controls. Patients were divided according to their response to corticosteroids: steroid-sensitive (SS, n = 8), or steroid-resistant (SR, n = 24). Immune mediators were also compared in regard with disease activity (relapse and remission). Immune mediators were measured by ELISA. Plasma TGF-beta1 levels in SR patients were approximately 2.8-fold higher than control values (p < 0.05). Urinary IL-8/CXCL8 was 2.9-fold higher in INS patients in relapse (proteinuria >100 mg/m2/24 h) when compared with patients in remission (p < 0.05), and levels had a positive correlation with individual proteinuria values (p < 0.05). Urinary IL-8/CXCL8 was significantly higher in relapsed SR than in SS patients in remission. No changes in MCP-1/CCL2 and RANTES/CCL5 levels were detected. Our findings suggest that IL-8/CXCL8 and TGF-beta1 are involved in the pathogenesis of INS: IL-8/CXCL8 associated with local changes in glomerular permeability and TGF-beta1 could be related to worse response to corticosteroids.
Asunto(s)
Factores Inmunológicos , Interleucina-8/inmunología , Síndrome Nefrótico , Proteinuria/inmunología , Adolescente , Quimiocina CCL2/sangre , Quimiocina CCL2/orina , Quimiocina CCL5/sangre , Quimiocina CCL5/orina , Niño , Femenino , Humanos , Factores Inmunológicos/sangre , Factores Inmunológicos/inmunología , Factores Inmunológicos/orina , Interleucina-8/sangre , Interleucina-8/orina , Masculino , Síndrome Nefrótico/metabolismo , Síndrome Nefrótico/fisiopatología , Proteinuria/sangre , Proteinuria/orina , Factor de Crecimiento Transformador beta1/sangre , Factor de Crecimiento Transformador beta1/orinaRESUMEN
Evidence that was obtained in several experimental models and in strains of hypertensive rats indicates that infiltration of inflammatory cells and oxidative stress in the kidney play a role in the induction and maintenance of hypertension. Similar evidence is lacking in human hypertension, at least in part, because immunosuppressive treatment is unjustified in patients with hypertension. For addressing this issue, patients who were prescribed by their private physicians mycophenolate mofetil (MMF) for the treatment of psoriasis or rheumatoid arthritis and had, in addition, grade I essential hypertension and normal renal function were studied. Eight patients were studied before MMF was started, during MMF treatment, and 1 mo after MMF treatment had been discontinued. Other treatments and diet were unchanged in the three phases of the study. MMF therapy was associated with a significant reduction in systolic, diastolic, and mean BP. Urinary excretion of TNF-alpha was reduced progressively by MMF treatment and increased after MMF was discontinued. Reduction of urinary malondialdehyde, TNF-alpha, and RANTES excretion during MMF administration did not reach statistical significance but had a direct positive correlation with the BP levels. These data are consistent with the hypothesis that renal immune cell infiltration and oxidative stress play a role in human hypertension.