The pathogenesis of dysplastic kidney in a urinary tract obstruction in the female fetal lamb

Abstract

Background/purpose: 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. The authors created a successful obstructive uropathy model in the female fetal lamb to demonstrate the differing pathogenesis of renal dysplasia.

Methods: Female fetal lambs at 60 and 90 days' gestation had their urethra and urachus ligated transabdominally and were delivered by cesarean section at 145 days (full term). Kidney length and cortical thickness were measured, and samples were examined histologically. In the lambs operated on at 90 days, the urine was collected at delivery and Na and CI were measured and compared with the results obtained from normal full-term lambs.

Results: Seven of 10 female lambs had hydronephrosis or dysplastic kidneys. The cortext to kidney length ratio was 10+/-3% in the 90-days hydronephrotic group versus 29+/-6% in the controls (P<.001). Morphologically, the 90-day model had dilatation of the collecting tubules with normal glomerular numbers. The 60-day model had tubular cysts with fibromuscular cuffing and reduced glomerular numbers. The fetal urine Na was 47+/-3.3 mmol/L in controls versus 78+/-24 mmol/L in the hydropnephrotic lambs (P<.05). The urine CI in these lambs was 38+/-8.6 mmol/L in controls versus 55+/-14.5 mmol/L in the hydronephrotic lambs (P<.05).

Conclusions: An obstructive uropathy model was created in female fetal lambs. There were no dysplastic changes in the kidneys in lambs operated on at 90 days' gestation, but there were definite dysplastic changes in those operated on at 60 days. Concentrations of Na and CI in the fetal urine are higher than normal in the 90-day model.