Vidal-Dos-Santos Marina, Armstrong-Jr Roberto, de Assis Ramos Mayara Munhoz, da Anunciação Lucas Ferreira, Ricardo-da-Silva Fernanda Yamamoto, Correia Cristiano de Jesus, Ottens Petra J, Moreira Luiz Felipe Pinho, Leuvenink Henri G D, Breithaupt-Faloppa Ana Cristina
Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.
Front Transplant. 2025 May 30;4:1595766. doi: 10.3389/frtra.2025.1595766. eCollection 2025.
Kidney perfusion is a tool that allows organs to be assessed before transplantation. After brain death (BD), hormonal dysfunction can compromise graft quality. Hormonal treatment of donors has shown positive outcomes, and treatment during ex vivo perfusion may be advantageous. The combination of 17β-estradiol (E2) and methylprednisolone (MP) has been shown to modulate inflammation in donors. Therefore, this study aims to evaluate treatment with E2 and MP during isolated perfusion of kidneys in brain-dead male and female rats.
Female and male Wistar rats were submitted to BD and maintained for 4 h. In the same animal, the right kidney [RK-no isolated perfusion of kidney (IPK)] was removed and stored, while the left kidney (LK-with IPK) had the ureter and the renal artery cannulated and flushed with 5 ml of cold saline. The LK was then taken directly to the IPK system for 90 min. Experimental groups were performed in both male and female: IPK (without treatment) and IPK + Treat (MP and E2 added to the perfusate). Perfusion was performed with a constant pressure of 100 mmHg, using William's Medium E supplemented with HEPES, creatinine, and albumin as perfusate. Perfusate and urine were collected, and flow measurements were recorded. After IPK, the LK was stored.
IL-6 was reduced in all perfused groups, regardless of treatment. In female IPK + Treat, there was a reduction in perfusion flow, followed by reduced creatinine clearance and Na excretion. No difference was observed in males in regards to treatment.
The combined treatment of E2 and MP during isolated kidney perfusion compromised kidney function in females. In males, no detrimental effects were observed. These results show a sex-dependent action of the proposed treatment.
肾脏灌注是一种在移植前评估器官的工具。脑死亡（BD）后，激素功能障碍会影响移植物质量。对供体进行激素治疗已显示出积极效果，而在体外灌注期间进行治疗可能更具优势。17β-雌二醇（E2）和甲基强的松龙（MP）的联合使用已被证明可调节供体的炎症反应。因此，本研究旨在评估在脑死亡的雄性和雌性大鼠肾脏离体灌注期间使用E2和MP进行治疗的效果。
将雄性和雌性Wistar大鼠诱导脑死亡并维持4小时。在同一只动物中，切除右肾[RK-未进行肾脏离体灌注（IPK）]并保存，而左肾（LK-进行IPK）的输尿管和肾动脉插管并用5毫升冷盐水冲洗。然后将LK直接放入IPK系统中90分钟。在雄性和雌性大鼠中均设置了实验组：IPK（未治疗）和IPK + 治疗组（在灌注液中添加MP和E2）。使用补充了HEPES、肌酐和白蛋白的威廉姆斯E培养基作为灌注液，在100 mmHg的恒定压力下进行灌注。收集灌注液和尿液，并记录流量测量值。IPK后，将LK保存。
无论治疗与否，所有灌注组中的白细胞介素-6均减少。在雌性IPK + 治疗组中，灌注流量降低，随后肌酐清除率和钠排泄减少。在雄性大鼠中，未观察到治疗方面的差异。
在肾脏离体灌注期间联合使用E2和MP会损害雌性大鼠的肾功能。在雄性大鼠中，未观察到有害影响。这些结果表明所提出的治疗具有性别依赖性作用。
