Establishment of a rat model of pediatric-to-adult kidney transplantation to study the early rapid compensatory growth of the grafts

Abstract

Pediatric donor kidneys show rapid compensatory development in morphology and function after being transplanted into adult recipients. Establishing an animal model that can simulate clinical pediatric-to-adult (P→A) kidney transplantation is important for studying the characteristics and potential mechanisms related to this rapid graft growth. In the P→A group, kidneys harvested from 3- to 4-week-old Sprague–Dawley (SD) rats weighing <50 g were transplanted into adult SD rats (300-400 g). Novel techniques were employed using recipient common iliac vessels for vascular anastomosis and ureter graft drag-in connection to the recipient bladder. As a control group, conventional kidney transplantation was performed between adult SD rats (A→A group). A total of 11 transplants were performed in the P→A group. Eight recipients survived to 28 days without obvious complications and were euthanized for graft harvesting and analysis. Ultrasonography showed that the renal grafts grew significantly faster in the P→A group than in the A→A group during the first 7 days after transplantation, and the size of the renal grafts in the two groups was similar on day 28. Histology revealed significant glomerular enlargement and cell proliferation in the pediatric donor kidneys, with signs of hyperfiltration injury but without podocyte proliferation. Proximal tubular epithelial cells (PTECs) in the P→A group showed significant cell proliferation and hypertrophy. This study has successfully established an animal model in rats with similar characteristics to clinical P→A kidney transplantation, providing a new tool for studying the pathophysiological changes and potential mechanisms of early rapid compensatory growth of the grafts after small pediatric donor kidneys were transplanted into size-mismatched large adult recipients.