Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Clinical Pharmacokinetics Laboratory, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.
Xenotransplantation. 2023 Mar;30(2):e12795. doi: 10.1111/xen.12795. Epub 2023 Feb 23.
With pig kidney xenotransplantation nearing clinical reality, it is imperative to measure pig kidney function in the graft recipients. Our aims were (i) to compare inulin clearance after a short intravenous (IV) bolus with steady-state inulin IV infusion, (ii) to use this method to measure the glomerular filtration rate (GFR), and (iii) to determine the tubular secretory function using cefoxitin in a pig-to-baboon renal transplant model. A short IV infusion of inulin and cefoxitin were followed by a maintenance IV infusion of inulin over 5 h in seven healthy baboons, three healthy pigs, and five baboons after bilateral native nephrectomy and intra-abdominal pig renal transplantation. Blood and urine samples were collected. Serum and urinary inulin and serum cefoxitin concentrations measured by validated assays were used to calculate GFR and renal secretion. GFR calculated were similar by both methods. The body weight normalized total body clearance of inulin was similar in pigs and baboons despite differences in absolute clearances. Pig kidney transplanted into baboons provided similar clearance in baboons when normalized to baboon body weight and sustained filtration and secretory functions. The study documented that pig kidneys support the physiologic needs of baboons and are likely to support human recipients as well.
随着猪肾异种移植接近临床现实,必须测量移植物受者的猪肾功能。我们的目的是:(i) 比较短时间静脉内(IV)推注与稳态 IV 输注后,菊粉清除率,(ii) 使用该方法测量肾小球滤过率(GFR),(iii) 在猪到狒狒肾移植模型中使用头孢西丁确定肾小管分泌功能。在 7 只健康狒狒、3 只健康猪和 5 只双侧原生肾切除和腹腔内猪肾移植后的狒狒中,进行了短时间 IV 输注菊粉和头孢西丁,随后进行了 5 小时的 IV 输注维持菊粉。采集血样和尿样。通过验证的检测测量血清和尿液中的菊粉和血清头孢西丁浓度,以计算 GFR 和肾脏分泌。两种方法计算的 GFR 相似。尽管绝对清除率存在差异,但猪和狒狒的体重标准化全身菊粉总清除率相似。当标准化为狒狒体重时,移植到狒狒体内的猪肾提供了与狒狒相似的清除率,并维持了滤过和分泌功能。该研究表明,猪肾能够满足狒狒的生理需求,并且可能也能满足人类受者的需求。