Assessment of glomerular filtration and tubular secretion in baboons with life-supporting pig kidney grafts

被引:11
作者
Hansen-Estruch, Christophe [1 ]
Bikhet, Mohamed H. [1 ]
Shaik, Imam H. [2 ,3 ]
Vasudevan, Vignesh [2 ]
Zhao, Wenchen [2 ]
Javed, Mariyam
Collins, Dalis E. [4 ]
Ayares, David [5 ]
Judd, Eric [6 ]
Cooper, David K. C. [1 ,8 ,10 ]
Venkataramanan, Raman [2 ,7 ,9 ]
机构
[1] Univ Alabama Birmingham, Dept Surg, Xenotransplantat Program, Birmingham, AL USA
[2] Univ Pittsburgh Sch Pharm, Clin Pharmacokinet Lab, Pittsburgh, PA USA
[3] Univ Pittsburgh Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA USA
[4] Univ Alabama Birmingham, Anim Resources Program, Birmingham, AL USA
[5] Revivicor, Blacksburg, VA USA
[6] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL USA
[7] Univ Pittsburgh, Starzl Transplantat Inst, Dept Pathol, Sch Med, Pittsburgh, PA USA
[8] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Transplantat Sci, Dept Surg, Boston, MA USA
[9] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA
[10] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA
关键词
baboon; glomerular filtration rate; kidney function; pig; tubular secretion; xenotransplantation; INJECTION;
D O I
10.1111/xen.12795
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
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页数:11
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