Gonzalez Alex, Delgado Rachel, de Caestecker Mark P
Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Semin Nephrol. 2025 Aug 23:151669. doi: 10.1016/j.semnephrol.2025.151669.
Many patients with urinary obstruction have an accelerated decline in renal function despite early urologic interventions. They also have defects in urinary concentrating capacity that may predispose them to acute kidney injury and chronic kidney disease. Because urinary concentrating capacity depends on having intact solute concentrating mechanisms in the renal medulla, it is likely that this results from obstruction-induced abnormalities in renal medullary structure, function, or both. This review focuses on findings from a recent study characterizing the long-term effects of reversible unilateral ureteral obstruction in mice that address these questions. These findings show that there is delayed long-term growth of the inner medulla, which is initially shrunken, that results in complete restoration of inner medullary size and gross tissue architecture 3 months after reversal of the obstruction. More detailed analysis shows that despite relatively normal histologic appearances, there are permanent defects in the cellular organization and function of the medulla that account for the loss of urinary concentrating capacity. We discuss the extent to which regenerative versus nonregenerative repair mechanisms may contribute to the growth and functional recovery of the renal medulla and consider how these findings shed light on the mechanisms of tissue repair and dysfunction after reversal of urinary obstruction.
许多尿路梗阻患者尽管早期接受了泌尿外科干预,但其肾功能仍加速衰退。他们的尿液浓缩能力也存在缺陷,这可能使他们易患急性肾损伤和慢性肾病。由于尿液浓缩能力取决于肾髓质中完整的溶质浓缩机制,因此这很可能是由梗阻引起的肾髓质结构、功能异常或两者兼而有之所致。本综述重点关注最近一项关于小鼠可逆性单侧输尿管梗阻长期影响的研究结果,该研究解决了这些问题。这些结果表明,最初萎缩的内髓质存在延迟的长期生长,在梗阻解除3个月后,内髓质大小和大体组织结构完全恢复。更详细的分析表明,尽管组织学外观相对正常,但髓质的细胞组织和功能存在永久性缺陷,这导致了尿液浓缩能力的丧失。我们讨论了再生与非再生修复机制在多大程度上可能有助于肾髓质的生长和功能恢复,并思考这些发现如何揭示尿路梗阻解除后组织修复和功能障碍的机制。