Laboratory of Small Animal Surgery 2, School of Veterinary Medicine, Kitasato University, Towada, Aomori, Japan.
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
PLoS One. 2021 Jan 15;16(1):e0231233. doi: 10.1371/journal.pone.0231233. eCollection 2021.
Chronic kidney disease leads to high morbidity rates among humans. Kidney transplantation is often necessary for severe symptoms; however, options for new curative treatments are desired because of donor shortage. For example, it has been established that the kidneys can efficiently generate urine after transplantation of the metanephros, ureter, and bladder as a group. After transplantation, the urine can indirectly flow into the recipient's bladder using a stepwise peristaltic ureter system method where the anastomosis is created via the recipient's ureter for urinary tract reconstruction. However, the growth of the regenerated metanephros varies significantly, whereas the time window for successful completion of the stepwise peristaltic ureter system that does not cause hydronephrosis of the metanephros with bladder (ureter) is quite narrow. Therefore, this study was conducted to periodically and noninvasively evaluate the growth of the transplanted metanephros, ureter, and bladder in rats through computed tomography and ultrasonography. The ultrasonographic findings highly correlated to the computed tomography findings and clearly showed the metanephros and bladder. We found that the degree of growth of the metanephros and the bladder after transplantation differed in each case. Most of the rats were ready for urinary tract reconstruction within 21 days after transplantation. Optimizing the urinary tract reconstruction using ultrasonography allowed for interventions to reduce long-term tubular dilation of the metanephros due to inhibited overdilation of the fetal bladder, thereby decreasing the fibrosis caused possibly by transforming growth factor-β1. These results may be significantly related to the long-term maturation of the fetal metanephros and can provide new insights into the physiology of transplant regeneration of the metanephros in higher animals. Thus, this study contributes to the evidence base for the possibility of kidney regeneration in human clinical trials.
慢性肾脏病导致人类发病率居高不下。对于严重症状，通常需要进行肾移植；但是，由于供体短缺，人们希望有新的治疗方法。例如，已经证实，将后肾、输尿管和膀胱作为一个整体移植后，肾脏可以有效地生成尿液。移植后，可以使用逐步蠕动输尿管系统方法，通过受者输尿管为尿路重建创建吻合口，使尿液间接流入受者膀胱，从而使尿液间接流入受者膀胱。然而，再生后肾的生长变化很大，而不引起后肾（输尿管）积水的逐步蠕动输尿管系统成功完成的时间窗口相当狭窄。因此，这项研究旨在通过计算机断层扫描和超声检查定期和非侵入性地评估大鼠移植后肾、输尿管和膀胱的生长情况。超声检查结果与计算机断层扫描结果高度相关，清楚地显示了后肾和膀胱。我们发现，移植后后肾和膀胱的生长程度在每个病例中都有所不同。大多数大鼠在移植后 21 天内即可准备进行尿路重建。使用超声检查优化尿路重建，可以减少由于胎儿膀胱过度扩张而导致的后肾长期管状扩张，从而减少可能由转化生长因子-β1 引起的纤维化。这些结果可能与胎儿后肾的长期成熟密切相关，并为高等动物后肾移植再生的生理学提供新的见解。因此，这项研究为人类临床试验中肾脏再生的可能性提供了证据基础。
