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

Author:

Hansen‐Estruch Christophe1ORCID,Bikhet Mohamed H.1,Shaik Imam H.23ORCID,Vasudevan Vignesh2,Zhao Wenchen2,Javed Mariyam1,Collins Dalis E.4,Ayares David5,Judd Eric6,Cooper David K. C.17ORCID,Venkataramanan Raman28ORCID

Affiliation:

1. Xenotransplantation Program, Department of Surgery University of Alabama at Birmingham Birmingham Alabama USA

2. Clinical Pharmacokinetics Laboratory University of Pittsburgh School of Pharmacy Pittsburgh Pennsylvania USA

3. Department of Pharmacy and Therapeutics University of Pittsburgh School of Pharmacy Pittsburgh Pennsylvania USA

4. Animal Resources Program University of Alabama at Birmingham Birmingham Alabama USA

5. Revivicor Blacksburg Virginia USA

6. Division of Nephrology Department of Medicine University of Alabama at Birmingham Birmingham Alabama USA

7. Center for Transplantation Sciences Department of Surgery Massachusetts General Hospital/Harvard Medical School Boston MA USA

8. Starzl Transplantation Institute and Department of Pathology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA

Abstract

AbstractWith 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.

Publisher

Wiley

Subject

Transplantation,Immunology

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