Fetal rhesus monkey model of obstructive renal dysplasia

Background. Disorders of kidney development represent a major cause of rena l failure and end-stage renal disease in the pediatric population. To under stand further the prenatal pathogenesis of obstructive renal dysplasia, a f etal monkey model was developed using ultrasound-guided techniques. Methods. Ureteropelvic obstruction (N = 13) was induced during the early or late second trimester by the injection of purified guluronic alginate sphe res. All fetuses were monitored sonographically, and then fetal tissues wer e removed at varying time points during the second and third trimesters. Results. There was no evidence of oligohydramnios during the course of gest ation, and the obstructed kidneys were typically progressively smaller than the contralateral (nonobstructed) kidneys when monitored sonographically o ver time. Obstructed kidneys displayed most features of renal dysplasia, in cluding numerous cortical cysts of various sizes derived predominantly from collecting ducts and glomeruli. Mesenchymal changes included expansion of both the cortical and medullary interstitium. as well as mesenchymal-myocyt e transformation. expressed as pericystic and peritubular fibromuscular col lar formation. An important feature of this model was the disruption of nor mal glomerular development and architecture, associated with significant po docyte apoptosis, evident as early as the prevascularized S-shaped nephron. As in other models, collecting duct cell apoptosis was apparent, particula rly in areas of cyst formation and cellular atrophy. Conclusions. These results demonstrate the: importance of this nonhuman pri mate model for exploring the pathophysiology of congenital obstructive urop athy and highlight the potential role of podocyte injury in determining lon g-term renal Function associated with this condition.