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Kidney Week

Abstract: TH-PO0899

Fetal-to-Fetal Kidney Transplantation: Novel Bridge Therapy for Congenital Kidney Diseases

Session Information

Category: Transplantation

  • 2101 Transplantation: Basic

Authors

  • Morimoto, Keita, Tokyo Jikeikai Ika Daigaku, Minato, Tokyo, Japan
  • Yamanaka, Shuichiro, Tokyo Jikeikai Ika Daigaku, Minato, Tokyo, Japan
  • Yamamoto, Shutaro, Tokyo Jikeikai Ika Daigaku, Minato, Tokyo, Japan
  • Koda, Nagisa, Tokyo Jikeikai Ika Daigaku, Minato, Tokyo, Japan
  • Kuroda, Takafumi, Tokyo Jikeikai Ika Daigaku, Minato, Tokyo, Japan
  • Ikeda, Takumi, Tokyo Jikeikai Ika Daigaku, Minato, Tokyo, Japan
  • Ohashi, Hinari, Tokyo Jikeikai Ika Daigaku, Minato, Tokyo, Japan
  • Seito, Toyoshi, Tokyo Jikeikai Ika Daigaku, Minato, Tokyo, Japan
  • Matsumoto, Kei, Tokyo Jikeikai Ika Daigaku, Minato, Tokyo, Japan
  • Ozawa, Katsusuke, Kokuritsu Kenkyu Kaihatsu Hojin Kokuritsu Seiiku Iryo Kenkyu Center, Setagaya, Tokyo, Japan
  • Wada, Seiji, Kokuritsu Kenkyu Kaihatsu Hojin Kokuritsu Seiiku Iryo Kenkyu Center, Setagaya, Tokyo, Japan
  • Kobayashi, Eiji, Tokyo Jikeikai Ika Daigaku, Minato, Tokyo, Japan
  • Yokoo, Takashi, Tokyo Jikeikai Ika Daigaku, Minato, Tokyo, Japan
Background

Fetuses with severe congenital kidney diseases, such as bilateral renal agenesis, often require immediate renal replacement therapy after birth. However, due to complications associated with prematurity, initiating dialysis is frequently unfeasible, leading to high neonatal mortality rates. To address this, we explored a novel therapeutic strategy involving the in utero transplantation of porcine fetal kidneys, aiming to serve as a temporary bridge until postnatal dialysis becomes viable.

Methods

Fetal kidneys were harvested from green fluorescent protein (GFP)-expressing Sprague–Dawley rats (embryonic day [E]14.0–16.5) and GFP-C57BL/6 mice (E13.0–13.5). These were transplanted transuterinely into fetal rats (E18.0–18.5). In the mouse-to-rat model, tacrolimus was administered to mitigate immune rejection. Postnatally, grafts were retrieved and assessed histologically for renal development and immune response. Urinary excretion was evaluated via percutaneous aspiration of distended bladders. Additionally, as a step toward clinical application, porcine fetal kidneys (E30) were transplanted into recipient fetal pigs (E83–95) with tacrolimus administration.

Results

Transplanted fetuses were delivered spontaneously and survived postnatally. GFP-positive grafts were successfully retrieved 3–4 weeks after transplantation, exhibiting developed glomerular and tubular structures. In the rat-to-rat model, no significant immune rejection was observed. Bladder distension indicative of urine production was noted, and sustained urinary output was confirmed through weekly percutaneous aspirations for up to 150 days. In the pig-to-pig model, successful graft engraftment and continuous urine production were observed for 97 days postnatally. While mild rejection was detected, glomerular and tubular structures remained intact.

Conclusion

This study is the first to demonstrate successful in utero transplantation of fetal kidneys in both rodent-to-rodent and pig-to-pig models, resulting in functional exogenous kidneys capable of sustained urine production. Further studies, including those involving non-human primate models, are underway to evaluate clinical applicability.

Digital Object Identifier (DOI)