INSULIN-LIKE GROWTH-FACTOR (IGF) AND IGF BINDING-PROTEIN GENE-EXPRESSION IN MULTICYSTIC RENAL DYSPLASIA

Multicystic dysplastic kidney disease is the most common form of renal dysplasia that leads to ESRD in children. This study describes the hi stopathological changes of multicystic dysplasia that occur from early fetal life to the postnatal period. At 14 wk gestation, early cystic enlargement of various segments of the nephron have been identified, i n addition to a displaced metanephric blastema adjacent to zones of no rmal nephrogenesis. At later stages, the predominant features include cyst enlargement with marked fibromuscular collars, architectural diso rganization, and replacement of the interstitium with a disarray of me senchymal tissue. This study investigated the expression of the mRNA e ncoding the insulinlike growth factors (IGF) and IGF binding proteins (IGFBP) and have demonstrated IGF-II, IGFBP-2, and IGFBP-3 to be alter ed. Apart from their expression in the displaced metanephric blastema, both IGF-II and IGFBP-2 were overexpressed in abnormal tissue element s in all kidneys from fetal to postnatal life. IGF-II gene expression was localized to mesenchymal tissue, specifically in the periductal fi bromuscular collars. IGFBP-2 mRNA was found to be expressed exclusivel y in the cyst epithelia of all cysts at all ages studied, whereas IGFB P-3 mRNA was absent from these epithelia. This study details the failu re of normal IGF expression in the development of multicystic renal dy splasia and suggests a role for the IGF system in the progressive hist opathological changes of this disorder.