García-Rojo Esther, Angulo Javier, El Assar Mariam, Santos-Pérez de la Blanca Rocío, García-Gómez Borja, Medina-Polo José, Sevilleja-Ortiz Alejandro, Rodríguez-Mañas Leocadio, Fernández Argentina, Gutiérrez-Martínez Eduardo, Morales-Ruiz Enrique, Rodríguez-Antolín Alfredo, Romero-Otero Javier
Department of Urology, Hospital Universitario HM Sanchinarro, HM Hospitales, 28050 Madrid, Spain.
Department of Histology-Research, Unidad de Investigación Traslacional en Cardiología (IRYCIS-UFV), Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.
Cells. 2025 Jul 1;14(13):1005. doi: 10.3390/cells14131005.
We aimed to determine the influence of donors' vascular function on renal function in recipients and to evaluate the role of Orai1 calcium channels as a potential marker. A prospective collaborative multicenter study was designed. Blood, aorta (HA), mesenteric arteries (HMAs) and corpus cavernosum (HCC) specimens were obtained from organ donors at the kidney procurement procedure (n = 60). Evolution (up to 2 years) of renal function measured as serum creatinine (SCr) and glomerular filtration rate (GFR) was evaluated in respective recipients (n = 64). Vascular responses were determined in HA, HMA and HCC from donors. Tumor necrosis factor-α, asymmetric dimethyl arginine and Orai1 were measured in plasma. Orai1 protein expression was also evaluated in each donor's aorta. Endothelium-dependent vasodilation (HMA, HCC) and adrenergic contraction (HA) in donors determined renal function in recipients, 12 months post-transplantation. Donors in the best quartile of vascular function predicted lower SCr and higher GFR in kidney recipients for 12/24 months. Plasma Orai1 in donors was negatively correlated with vascular function and predicted renal function at 3-6 months post-transplantation. Donor Orai1 vascular content was associated with reduced vascular function and with poorer recipient renal function for 1-year post-transplantation. Systemic vascular function of kidney donors determines recipients' renal function at short/mid-term. Donors' vascular function and recipients' renal function are negatively associated with donors' Orai1 vascular expression, being a potential biomarker of renal outcomes.
我们旨在确定供体血管功能对受体肾功能的影响，并评估Orai1钙通道作为潜在标志物的作用。设计了一项前瞻性协作多中心研究。在肾脏获取手术中从器官供体获取血液、主动脉（HA）、肠系膜动脉（HMA）和海绵体（HCC）标本（n = 60）。在各自的受体（n = 64）中评估以血清肌酐（SCr）和肾小球滤过率（GFR）衡量的肾功能演变（长达2年）。测定供体HA、HMA和HCC中的血管反应。测量血浆中的肿瘤坏死因子-α、不对称二甲基精氨酸和Orai1。还评估每个供体主动脉中的Orai1蛋白表达。供体的内皮依赖性血管舒张（HMA、HCC）和肾上腺素能收缩（HA）决定了移植后12个月受体的肾功能。血管功能处于最佳四分位数的供体预测肾移植受体在12/24个月时SCr较低且GFR较高。供体血浆中的Orai1与血管功能呈负相关，并预测移植后3 - 6个月的肾功能。供体Orai1血管含量与血管功能降低以及移植后1年受体肾功能较差有关。肾供体的全身血管功能在短期/中期决定受体的肾功能。供体的血管功能和受体的肾功能与供体Orai1血管表达呈负相关，Orai1是肾脏预后的潜在生物标志物。
