RESUMEN
BACKGROUND: Low birth weight is associated with deficits in nephron number in the infant kidney and increased risk of adulthood hypertension and renal dysfunction. Urinary biomarkers may be potential indicators of renal reserve, but little is known about the influence of gestational and postnatal age on the expression of urinary proteins. The aims of this study were to determine the relationships between selected urinary proteins and renal maturation. We hypothesized that urinary protein patterns would change over time during late nephrogenesis and renal maturation. METHODS: Urine samples were collected at birth and over 12 mo from preterm (33-35 wk) and term (38-40 wk) infants. Candidate urinary proteins were identified by antibody array and quantified with enzyme-linked immunosorbent assay. RESULTS: Preterm infants at birth were found to have relatively elevated levels of insulin-like growth factor binding protein-1, -2, and -6, monocyte chemotactic protein-1, CD14, and sialic acid-binding Ig-like lectin 5. These markers gradually decline to levels similar to those of full-term infants by 2-6 mo of life. In contrast, many urinary markers in healthy full-term infants remain stable over the first year of life. CONCLUSION: Gestational and postnatal age must be considered when evaluating the utility of urinary biomarkers.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica/genética , Recien Nacido Prematuro/metabolismo , Riñón/crecimiento & desarrollo , Riñón/metabolismo , Proteinuria/orina , Proteoma/genética , Factores de Edad , Antígenos CD/orina , Antígenos de Diferenciación Mielomonocítica/orina , Quimiocina CCL2/orina , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/orina , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/orina , Proteína 6 de Unión a Factor de Crecimiento Similar a la Insulina/orina , Lectinas/orina , Masculino , Estadísticas no ParamétricasRESUMEN
The glomerular microenvironment is influenced by circulating growth factors that are filtered from the blood stream and pass the glomerular filtration barrier. In this study, we wanted to explore the role of IGF-binding proteins (IGFBPs) in two diseases that concern podocytes. We analyzed glomerular expression and urinary excretion of IGFBP-1, -2, and -3 in patients with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). We found that patients with active FSGS excrete high amounts of podocalyxin positive cells as well as IGFBP-1 and -3. In human podocytes, we can induce mRNA expression of IGFBP-3 in response to TGF-beta and in human microvascular endothelial cells expression of IGFBP-1 and -3 in response to TGF-beta and Bradykinin. We conclude that the local expression of IGFBPs in podocytes and endothelial cells might contribute to the pathogenesis of glomerular disease and that IGFBP-1 and -3 are potential non-invasive markers of FSGS.