Chevalier R L
Department of Pediatrics, University of Virginia, School of Medicine, Charlottesville 22908, USA.
Semin Nephrol. 1995 Jul;15(4):353-60.
Renal insufficiency due to congenital obstructive nephropathy is a consequence of arrested or abnormal renal growth. A number of experimental studies have shown that the younger the age at the time of unilateral ureteral obstruction (UUO), the more severe the growth impairment of the ipsilateral kidney, and the greater the compensatory growth of the opposite kidney ("counterbalance"). Urinary obstruction in early fetal life results in renal dysplasia and a decrease in the number of functioning nephrons. The renin-angiotensin system is highly activated in early development, and UUO further increases this activity, resulting in vasoconstriction and glomerular contraction. Long-term UUO also causes progressive interstitial fibrosis, which presumably contributes to arrested growth of the kidney. This may result from excessive deposition of extracellular matrix stimulated by increased expression of transforming growth factor-beta 1. Neonatal UUO delays the expression of epidermal growth factor, and prolongs the expression of peritubular alpha smooth muscle actin, suggesting that renal maturation is delayed by UUO. Renal apoptosis is increased by UUO, which may contribute to the reduced DNA content of the neonatal obstructed kidney. Renal expression of clusterin, a glycoprotein associated with cell adhesion and protection from apoptosis, is increased by ipsilateral UUO, and also presumably modulates renal growth. Thus, renal growth and development are impaired by UUO through complex interactions between regulators of cell proliferation, cell destruction, and extracellular matrix.
先天性梗阻性肾病所致的肾功能不全是肾脏生长停滞或异常的结果。多项实验研究表明，单侧输尿管梗阻（UUO）时年龄越小，同侧肾脏的生长损害越严重，对侧肾脏的代偿性生长（“平衡”）就越大。胎儿早期的尿路梗阻会导致肾发育不全和功能性肾单位数量减少。肾素-血管紧张素系统在早期发育中高度激活，而UUO会进一步增加这种活性，导致血管收缩和肾小球收缩。长期的UUO还会导致进行性间质纤维化，这可能导致肾脏生长停滞。这可能是由于转化生长因子-β1表达增加刺激细胞外基质过度沉积所致。新生儿UUO会延迟表皮生长因子的表达，并延长肾小管周围α平滑肌肌动蛋白的表达，提示UUO会延迟肾脏成熟。UUO会增加肾脏细胞凋亡，这可能导致新生儿梗阻性肾脏的DNA含量降低。同侧UUO会增加与细胞黏附及抗细胞凋亡相关的糖蛋白簇集素的肾脏表达，其也可能调节肾脏生长。因此，UUO通过细胞增殖、细胞破坏和细胞外基质调节因子之间的复杂相互作用损害肾脏的生长和发育。
