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BSP-9

(P)

URINARY TRACT OBSTRUCTION AND REDUCED NEPHRON NUMBER: ADAPTATION

OF NEPHRONS FOLLOWED THROUGH ADULTHOOD IN A MOUSE MODEL

Maria SERGIO

Pediatric Surgery, Dipartimento Materno Infantile, Palermo, ITALY

PURPOSE

Congenital urinary tract obstruction affects renal development and maturation, often leading to chronic kidney disease

(CKD). Associated with CAKUT (congenital anomalies of kidneys and urinary tract), reduced nephron number (NN) at

birth is an independent risk factor for adult CKD. (Luyckx VA at al. Lancet 2013; 382: 273). We aimed to examine the

behavior of nephrons in adult mice with reduced NN subjected to partial unilateral ureteral obstruction (UUO)

MATERIAL AND METHODS

Wild-type (WT) and Os/+ mice (with 50% fewer nephrons) were subjected to sham operation or partial UUO in the first

2 days of life. Additional mice underwent release of UUO at 7 days. All kidneys were harvested at 3 weeks (weaning) or

6 weeks (adulthood). Parameters evaluated by histomorphometry were: glomerular number and area, glomerulotubular

junction integrity, proximal tubular volume fraction, and interstitial fibrosis.

RESULTS

In Os/+ mice, NN decreased further in the UUO kidney, and glomerular growth from 21 to 42 days of Os/+ mice was

impaired, regardless of the release of UUO. Whereas UUO impaired maturation of the glomerulotubular junction and

proximal tubular growth in all mice, release of obstruction preserved these in wild-type mice only. Interstitial collagen

accumulated after 42 days of ipsilateral UUO, decreased following release of obstruction in wild-type, but not Os/+ mice.

CONCLUSIONS

Suppression of nephron growth and maturation by UUO is more severe in mice with reduced NN, and release of

obstruction is less effective in reversing obstructive renal injury . Children with prematurity and congenital urinary tract

obstruction are at increased risk to develop CKD.