Evolution of the urinary proteome during human renal development and maturation: variations with gestational and postnatal age.

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.

IGFs and IGF-binding proteins in short children with steroid-dependent nephrotic syndrome on chronic glucocorticoids: changes with 1 year exogenous GH.

OBJECTIVE: Children with steroid-dependent nephrotic syndrome (SDNS), despite being in remission on glucocorticoids, continue to have growth retardation and short stature. The mechanism is uncertain as both chronic glucocorticosteroids and the nephrotic syndrome may independently affect growth. We investigated the changes in the IGFs and IGF-binding proteins (IGFBPs) in a group of short SDNS children, and studied the changes prospectively with 1 year's treatment with GH. DESIGN AND METHODS: Total and 'free' IGF-I, IGFBP-3 and acid-labile subunit (ALS) were studied in eight SDNS boys (mean age=12.6 years; mean bone age=9.1 years) on long term oral prednisolone (mean dose 0.46 mg/kg per day) before, during, and after, 1 year's treatment with GH (mean dose 0.32 mg/kg per week). Pretreatment comparisons were made with two control groups, one matched for bone age (CBA; mean bone age=9.2 years), and another for chronological age (CCA; mean chronological age=13 years). Subsequently, three monthly measurements of serum and urine IGFBPs were carried out in the GH-treated SDNS patients using Western ligand blot and Western immunoblot. RESULTS: Pre-treatment serum total IGF-I levels and the IGF-I/IGFBP-3 ratio were elevated significantly in SDNS compared with CBA, and were similar to CCA. Serum free IGF-I levels were elevated significantly compared with both control groups, but serum IGFBP-3 did not differ significantly. Urinary IGFBP-2, IGFBP-3 and ALS were detectable in the SDNS children only. With GH treatment, IGF-I and IGFBP-3, but not IGF-II, increased significantly compared with pre-treatment values, and returned to baseline after cessation of GH treatment. Urinary IGFBPs did not change significantly with GH treatment. CONCLUSIONS: There is persistent urinary loss of IGFBP-2, IGFBP-3 and ALS in children with SDNS in remission with growth retardation. However, the significant elevation in serum IGF-I suggests that glucocorticoid-induced resistance to IGF is the main factor responsible for the persistent growth retardation in these children. Exogenous GH was able to overcome this resistance by further increasing serum IGF-I.