超低出生体重児53名の25.5%に糸球体障害を, 82.6%に尿細管障害を認め, 出生体重との相関を確認した。続いて母胎低栄養ラット(NR)胎仔後腎において尿管芽分枝と糸球体数の減少を, その原因として尿管芽分枝に関与する遺伝子のメチル化の変化を認めた。さらに成熟後のNRラット仔が, 片側尿管結紮により尿細管壊死を伴う腎障害を呈すことを確認した。
子宮内劣悪環境を経た超低出生体重児の腎機能障害, 特に尿細管障害についての報告は少なく, 本成果はその原因が胎児プログラミングにあり, また成長後の二次的侵襲の影響もより強く受けることを示した。今後, 新生児医療において腎機能障害に着目したフォローアップが必要である。
The number of low birth weight babies, products of intra uterine growth retardation (IUGR), is increasing in Japan. Those IUGR survivors are known to develop metabolic syndrome in adult life due to probable reduced kidney function. We studied glomerular and tubular function of 53 extremely low birth weight subjects (ELBW). Twenty five percent of subjects had glomerular dysfunction and eighty three percent of them had tubular dysfunction. We showed that maternal nutritional restriction, NR, leads to reduced ureteric branching resulted in low nephron number of rat embryos. In those embryos, DNA methylation of genes involved in ureteric branching has been changed, which may contribute to reduced nephron number and transgenerational transmission. Further, we found the kidney of offsprings from NR rats were more susceptible to ischemia and fibrosis secondary to unilateral ureteral obstruction. The results have pointed out necessity of careful follow-up of kidney function for those premies.
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