CHARACTERIZATION OF FETAL OVINE RENAL DYSPLASIA AFTER MIDGESTATION URETERAL OBSTRUCTION

Objective: The etiology and pathogenesis of renal dysplasia are poorly understood. To characterize the histologic changes in fetal renal dys plasia, we studied a fetal ovine model of urinary obstruction. Design: Animal study. Animals: Seven fetal lambs, and other lambs of the same gestational age as controls. Interventions: Unilateral ureteral ligat ion on fetal lambs at approximately 70 days' gestation (term for sheep is 145 days), during nephrogenesis. Kidneys were subsequently collect ed, examined histologically and characterized by immunohistochemical t ests involving cytokeratin antiserum and a monoclonal antibody to alph a-actin. Outcome measures: Histologic changes in ligated fetal lamb ki dneys, based on comparison with normal fetal lamb kidneys. Results: At near term (140 days' gestation), the ligated kidney showed distorted and less abundant renal parenchyma than a normal control kidney. Upon microscopic examination, the ligated kidney displayed marked architect ural distortion of the outer cortex, with abundant interstitial fibros is, primitive ductules and glomeruli, and cysts of varying sizes lined by squamous and cuboidal epithelia and surrounded by a loose mesenchy me. The renal medulla contained differentiated collecting ducts, which were structurally distorted and less abundant than in normal control kidneys. The proximal and distal tubule elements were primitive and ma rkedly underdeveloped. Cytokeratin immunoreactivity was present in the collecting duct epithelium and in the cuboidal epithelium lining many of the cortical cysts. Smooth muscle alpha-actin immunoreactivity was localized in the cortical region of the kidney, which highlighted the abundance and disorganization of the undifferentiated mesenchyme and identified the fibromuscular collars of the primitive ductules of the cortex and the distorted collecting ducts of the medulla. Conclusions: These results highlight the histologic changes resulting from unilate ral ureteral ligation in fetal lambs. This model is useful in the stud y of the pathogenesis of fetal obstructive renal dysplasia.