Min Catherine, Galons Jean-Philippe, Lynch Ronald M, Steyn Leah V, Price Nicholas D, Weegman Brad P, Taylor Michael J, Pandey Abhishek, Harland Robert, Martin Diego, Besselsen David, Putnam Charles W, Papas Klearchos K
Department of Physiology, University of Arizona, Tucson, AZ, United States.
Department of Surgery, University of Arizona, Tucson, AZ, United States.
Front Transplant. 2024 Aug 22;3:1420693. doi: 10.3389/frtra.2024.1420693. eCollection 2024.
Transplantation of kidneys from expanded criteria donors (ECD), including after circulatory death (DCD), is associated with a higher risk of adverse events compared to kidneys from standard criteria donors. In previous studies, improvements in renal transplant outcomes have been seen when kidneys were perfused with gaseous oxygen during preservation (persufflation, PSF). In the present study, we assessed ex-vivo renal function from a Diffusion Contrast Enhanced (DCE)-MRI estimation of glomerular filtration rate (eGFR); and metabolic sufficiency from whole-organ oxygen consumption (WOOCR) and lactate production rates.
Using a porcine model of DCD, we assigned one kidney to antegrade PSF, and the contralateral kidney to static cold storage (SCS), both maintained for 24 h at 4°C. Post-preservation organ quality assessments, including eGFR, WOOCR and lactate production, were measured under cold perfusion conditions, and biopsies were subsequently taken for histopathological analysis.
A significantly higher eGFR (36.6 ± 12.1 vs. 11.8 ± 4.3 ml/min, < 0.05), WOOCR (182 ± 33 vs. 132 ± 21 nmol/min*g, < 0.05), and lower rates of lactate production were observed in persufflated kidneys. No overt morphological differences were observed between the two preservation methods.
These data suggest that antegrade PSF is more effective in preserving renal function than conventional SCS. Further studies in large animal models of transplantation are required to investigate whether integration with PSF of WOOCR, eGFR or lactate production measurements before transplantation are predictive of post-transplantation renal function and clinical outcomes.
与标准标准供体的肾脏相比,扩大标准供体(ECD)的肾脏移植,包括循环死亡后(DCD)供体的肾脏移植,与更高的不良事件风险相关。在先前的研究中,当肾脏在保存期间用气态氧灌注(吹入法,PSF)时,肾移植结果有所改善。在本研究中,我们通过扩散对比增强(DCE)-磁共振成像(MRI)评估肾小球滤过率(eGFR)来评估离体肾功能;并通过全器官氧消耗率(WOOCR)和乳酸产生率评估代谢充足性。
使用猪DCD模型,我们将一侧肾脏进行顺行PSF,对侧肾脏进行静态冷藏(SCS),两者均在4°C下保存24小时。在冷灌注条件下测量保存后器官质量评估指标,包括eGFR、WOOCR和乳酸产生,随后进行活检以进行组织病理学分析。
在吹入法保存的肾脏中,观察到eGFR显著更高(36.6±12.1对11.8±4.3ml/min,P<0.05),WOOCR显著更高(182±33对132±21nmol/min*g,P<0.05),并且乳酸产生率更低。两种保存方法之间未观察到明显的形态学差异。
这些数据表明,顺行PSF在保存肾功能方面比传统的SCS更有效。需要在大型动物移植模型中进行进一步研究,以调查在移植前将WOOCR、eGFR或乳酸产生测量与PSF相结合是否可预测移植后肾功能和临床结果。