Characterization of fetal ovine renal dysplasia after mid-gestation ureteral obstruction

Abstract

Objective: The etiology and pathogenesis of renal dysplasia are poorly understood. To characterize the histologic changes in fetal renal dysplasia, 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 ligation on fetal lambs at approximately 70 days' gestation (term for sheep is 145 days), during nephrogenesis. Kidneys were subsequently collected, examined histologically and characterized by immunohistochemical tests involving cytokeratin antiserum and a monoclonal antibody to alpha-actin.

Outcome measures: Histologic changes in ligated fetal lamb kidneys, 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 architectural distortion of the outer cortex, with abundant interstitial fibrosis, primitive ductules and glomeruli, and cysts of varying sizes lined by squamous and cuboidal epithelia and surrounded by a loose mesenchyme. 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 markedly 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 unilateral ureteral ligation in fetal lambs. This model is useful in the study of the pathogenesis of fetal obstructive renal dysplasia.