■人类肾脏发生通常在妊娠36周时完成;然而,它受到早产的影响。早期研究表明,早产儿的肾脏发生持续≤40天。然而,存活>40天的早产儿的月经后年龄(PMA)不确定.在这项研究中,我们试图重新检查存活>40天的早产儿的出生后肾脏发育.
■从机构生物库获得人肾样品。如果出生后存活≤4天,PMA为30至≤36周,则将样品视为对照。将出生后存活>40天和PMA为30至≤36周的早产儿的肾脏与对照组进行比较。我们数过肾小球世代,测量的肾变区宽度(NZW),并用SIX1和RET进行免疫荧光(IF)。我们比较了肾脏重量并量化了近端(莲花凝集素[LTL],SL22A2),远端(SLC12A3,KCNJ10),和使用IF的肾小球(nephrin)标记。
■分析了7名存活>40天的早产儿和8名对照。7名早产儿中有4名具有肾脏发生的组织学和分子证据。早产儿肾发生的停止比PMA匹配的对照组早2周,SIX1和RET的表达均减弱。我们发现肾脏的体重与体重比增加,浅表肾单位的远端肾小管横截面染色增加,早产儿肾脏远端肾小管肥大和增生。
■我们的研究支持,早产儿的肾脏发生持续时间比以前认为的更长,有证据表明早期肾单位应激,重视新生儿环境。
UNASSIGNED: Human nephrogenesis is typically completed by 36 weeks gestation; however, it is impacted by preterm birth. Early studies suggested that nephrogenesis persisted for ≤40 postnatal days in preterm infants. However, the postmenstrual age (PMA) of the preterm infants who survived >40 days was uncertain. In this study, we sought to reexamine postnatal kidney development in preterm infants surviving >40 days.
UNASSIGNED: Human kidney samples were obtained from an institutional biobank. Samples were considered controls if survival was ≤4 days after birth with PMA of 30 to ≤36 weeks. Kidneys from preterm neonates with postnatal survival >40 days and PMA of 30 to ≤36 weeks were compared to controls. We counted glomerular generations, measured nephrogenic zone widths (NZW), and performed immunofluorescence (IF) with SIX1 and RET. We compared kidney weights and quantified the cross-sectional area of proximal (lotus tetragonolobus lectin [LTL], SL22A2), distal (SLC12A3, KCNJ10), and glomerular (nephrin) markers using IF.
UNASSIGNED: Seven preterm infants surviving >40 days and 8 controls were analyzed. Four of 7 preterm infants had histologic and molecular evidence of nephrogenesis. Cessation of nephrogenesis in preterm infants occurred 2 weeks earlier than PMA-matched controls with attenuated expression of both SIX1 and RET. We found increased kidney weight-to-body weight ratio, increased distal tubular cross-sectional staining in the superficial nephrons, and distal tubular hypertrophy and hyperplasia in the preterm infant kidneys.
UNASSIGNED: Our study supports that nephrogenesis in preterm infants persists longer than previously thought with evidence of early nephron stress, placing importance on the neonatal environment.