The pathogenesis of dysplastic kidney in a urinary tract obstruction in fetal lambs

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Hypothesis : The type of renal dysplasia resulting from obstructive uropathy depends on the completeness of the obstruction and its timing with respect to the stage of glomerulogenesis at the time of the obstruction. We created a successful obstructive uropathy model in the fetal lamb to demonstrate the differing pathogenesis of renal dysplasia.Methods : Fetal lambs at 50, 60 and 90 days gestation were operated on. Male lambs underwent urethral and urachal ligation and female lambs had their urethra and urachus ligated transabdominally and created a similar to posterior urethral valve model (PUV). Some of the female lambs, unilateral ureteric ligation and created a vesico ureteric junction stenosis model (VUJ). They were returned to the uterus after the fetal surgery and delivered by cesarean section at 145 days (term).Results : Of 12 lambs operated on at 50 days gestation, 4 survived. Of 26 lambs operated on at 60 days, 21 survived. We identified 3 types of dysplastic kidneys. Type A : Fibrotic kidneys (2.2 gm) with no cysts and interstitial fibrosis. There were reduced numbers of proximal tubules but distal tubules and collecting ducts persisted. (50-day obstruction). Type B : Sponge-like kidneys (37 g) These had large cysts with minimal interstitial fibrosis. (87 % of 60 day uretheral and urachal ligation model n=12) Type C : Small kidneys (4.8 g) with no large cysts (60 day Ureteric ligation model n=7). Of 10 lambs operated at 90 days gestation had hydronephrosis without dysplastic kidney.Conclusion : All had dysplastic changes operated at 50 and 60 days gestation but most of the 60-day lambs with urethral and urachal ligation had enlarged kidneys with phenotypic features reminiscent of adult type polycystic kidney disease.