Avaliação de biomarcadores em pacientes pediátricos com refluxo vesicoureteral

Abstract

Vesicoureteral reflux (VUR) is the fourth most common cause of chronic kidney disease (CKD) in children. The management of VUR patients involves the use of continuous antibiotic prophylaxis, treatment of lower urinary tract dysfunction and, in selected cases, surgical approach, to avoid or at least delay progression to CKD. The great challenge in the management of VUR patients is to identify those at potential risk of end-stage renal disease. Studies on the pathophysiology of reflux nephropathy are scarce and clinically significant biomarkers have not yet been determined. There are several clinical and experimental findings on the role of inflammation in kidney disease. Assessing the effects of cytokines, chemokines, growth factors, and cell adhesion molecules on the onset and progression of kidney injury is therefore essential for the development of new prognostic markers and new therapeutic targets. An extensive review of the literature showed that the fibrogenic cytokine, TGF-β, the anti-inflammatory cytokine, IL-10, and the proinflammatory cytokines, IL-6, IL-8, and TNF, should be more intensively evaluated as potential biomarkers for renal scarring and for progression to CKD in reflux nephropathy. IL-1β should also be further investigated in VUR patients, since this cytokine seems to play an important role in acute phase of pyelonephritis and might prevent the formation of renal scarring. CCL2/MCP-1 might be an early biomarker of progressive renal damage and might have a potential role in predicting the long-term renal outcome. Growth factors and cellular adhesion molecules are also involved in the physiopathology of reflux nephropathy. In this regard, the cellular adhesion molecules ICAM-1 and the growth factors, FGF and VEGF, should be assessed as potential biomarkers for reflux nephropathy. Whereas VCAM appears to be associated with reflux severity, independent of progression to renal scarring. The objective of this study was to identify clinically relevant non-invasive biomarkers in pediatric patients with primary VUR. Inflammatory factors were investigated in the urine of VUR patients compared to healthy controls. All biomarkers were assessed simultaneously by flow cytometry method. It was showed that the inflammatory molecules MCP-1, IL-12p70, TNF, VEGF, and the anti-inflammatory IL-10 were highly increased in urine samples of VUR patients. In those VUR patients with CKD ≥ 3, we also observed elevated urinary levels of CXCL9/MIG, IL-8, FGF, and VCAM-1. Further studies are needed to identify within this group of proteins and polypeptides those molecules with the potential to become biomarkers capable of assisting in clinical decisions. Moreover, perhaps a panel of biomarkers composed of a combination of pro-inflammatory and anti-inflammatory factors would have greater accuracy in predicting the risk of progression to CKD than the measurement of a single marker.