Fetal rhesus monkey model of obstructive renal dysplasia.
BACKGROUND
Disorders of kidney development represent a major cause of renal failure and end-stage renal disease in the pediatric population. To understand further the prenatal pathogenesis of obstructive renal dysplasia, a fetal 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 spheres. All fetuses were monitored sonographically, and then fetal tissues were removed at varying time points during the second and third trimesters.


RESULTS
There was no evidence of oligohydramnios during the course of gestation, and the obstructed kidneys were typically progressively smaller than the contralateral (nonobstructed) kidneys when monitored sonographically over time. Obstructed kidneys displayed most features of renal dysplasia, including 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-myocyte transformation, expressed as pericystic and peritubular fibromuscular collar formation. An important feature of this model was the disruption of normal glomerular development and architecture, associated with significant podocyte apoptosis, evident as early as the prevascularized S-shaped nephron. As in other models, collecting duct cell apoptosis was apparent, particularly in areas of cyst formation and cellular atrophy.


CONCLUSIONS
These results demonstrate the importance of this nonhuman primate model for exploring the pathophysiology of congenital obstructive uropathy and highlight the potential role of podocyte injury in determining long-term renal function associated with this condition.
Tarantal
A F
AF
California Regional Primate Research Center, University of California, Davis, California 95616-8542, USA. aftarantal@primate.ucdavis.edu
Han
V K
VK
Cochrum
K C
KC
Mok
A
A
daSilva
M
M
Matsell
D G
DG
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000502:physiology; D007668:Kidney / Q000000981:diagnostic imaging / Q000196:embryology / Q000473:pathology; D008253:Macaca mulatta / Q000196:embryology; D016216:Ultrasonography, Prenatal; D014517:Ureteral Obstruction / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*