"Evolving Urinary Biomarkers in Premature Infants during Renal Maturation."

Background: Evidence suggests prematurity and low birth weight are associated with nephron deficits in the infant kidney leading to affected adults who are at increased risk of hypertension and renal dysfunction. Serum creatinine is a poor marker for renal injury and reserve, making it vital to discover other markers to monitor renal development and injury in an environment of dynamic developmental change. Objective: We wished to determine the role of gestational age in the pattern of urinary protein excretion during postnatal maturation. Results will reveal normal developmental patterns for infants, provide insight into effects of prematurity on renal development, and provide a basis for targeted investigations into molecular pathways in health and disease. Methods: Urine samples were collected at birth and at six months of age from healthy preterm (gestational age 33-35 weeks, n=8) and term infants (38-40 weeks, n=8). Urinary proteins were identified with an antibody array that detects 174 proteins using fluorescence detection. Relative fluorescence intensity (RFI) was normalized to urine creatinine. Results were stratified to select candidate biomarkers. Nineteen highly expressed biomarkers were compared between: 1. Preterm vs. term at birth and six months (Mann Whitney test), and 2. Within each group over time (Wilcoxon signed rank test). Significance was determined as p<0.05. 2 Patterns of Urinary Proteins as Potential Biomarkers of Renal Development and Function in Healthy Preterm and Full Term Infants. Jennifer Charlton, MD 4/30/2010 Results: At birth fourteen of 19 cytokines were significantly higher in the preterm group compared to the full term group at birth. Three of 19 cytokines decreased in the preterm infant group from birth to 6 months of age: IGFBP-1 (median: birth1545 RFI, 6 mo-311 RFI), CD14 (median: birth-437 RFI, 6 mo-219 RFI), and Siglec-5 (median: birth-2028 RFI, 6 mo-11 RFI). Thirteen increased in full term infants from birth to 6 months. At six months, there were no differences between the groups. Conclusion: Urinary protein panels in preterm and term infants differ at birth and there is no statistically significance differences between the groups exist at six months of age. We speculate that healthy premature infants "catch up" to term infants with respect to urinary biomarkers of renal development. These time-dependent and developmentally regulated changes make determination of age-dependent normal values mandatory in evaluation of childhood renal disease. 3 Patterns of Urinary Proteins as Potential Biomarkers of Renal Development and Function in Healthy Preterm and Full Term Infants.

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