Institute of Human Genetics, Department of General, Visceral and Cancer Surgery, University of Cologne, and Division of Pediatric Nephrology, Department of Pediatric and Adolescent Medicine, University Hospital Cologne, Cologne, Germany.
Nephrol Dial Transplant. 2012 Jul;27(7):2984-9. doi: 10.1093/ndt/gfr776. Epub 2012 Jan 28.
The infantile form of primary hyperoxaluria type I (PHI) is the most devastating PH subtype leading to early end-stage renal failure and severe systemic oxalosis. Combined or sequential liver-kidney transplantation (LKTx) is the only curative option but it involves substantial risks, especially in critically ill infants. The procedure also requires resources that are simply not available to many children suffering from PHI worldwide. Less invasive and less complex therapeutic interventions allowing a better timing are clearly needed. Liver cell transplantation (LCT) may expand the narrow spectrum of auxiliary measures to buy time until LKTx for infants can be performed more safely.
We performed LCT (male neonate donor) in a 15-month-old female in reduced general condition suffering from systemic oxalosis. Renal replacement therapy, initiated at the age of 3 months, was complicated by continuous haemodialysis access problems. Living donor liver transplantation was not available for this patient. Plasma oxalate (Pox) was used as the primary outcome measure.
Pox decreased from 104.3±8.4 prior to 70.0±15.0 μmol/L from Day 14 to Day 56 after LCT. A significant persistent Pox reduction (P<0.001) comparing mean levels prior to (103.8 μmol/L) and after Day 14 of LCT until LKTx (77.3 μmol/L) was seen, although a secondary increase and wider range of Pox was also observed. In parallel, the patient's clinical situation markedly improved and the girl received a cadaveric LKTx 12 months after LCT. However, biopsy specimens taken from the explanted liver did not show male donor cells by amelogenin polymerase chain reaction.
With due caution, our pilot data indicate that LCT in infantile oxalosis warrants further investigation. Improvement of protocol and methodology is clearly needed in order to develop a procedure that could assist in the cure of PHI.
婴儿型原发性高草酸尿症 I 型（PHI）是最具破坏性的 PH 亚型，可导致早期终末期肾衰竭和严重的全身性草酸中毒。联合或序贯肝肾移植（LKTx）是唯一的治愈选择，但它涉及到大量的风险，尤其是对于病危的婴儿。该手术还需要资源，而全世界许多患有 PHI 的儿童根本无法获得这些资源。显然，需要更微创和不那么复杂的治疗干预措施，以便更好地把握时机。肝细胞移植（LCT）可以扩大辅助措施的范围，为 LKTx 争取更安全的时机。
我们对一名患有全身性草酸中毒的 15 个月大、身体状况较差的女婴进行了 LCT（男性新生儿供体）。该患儿在 3 个月大时开始进行肾脏替代治疗，但持续存在血液透析通路问题。由于各种原因，该患者无法进行活体供肝移植。我们将血浆草酸盐（Pox）作为主要的观察指标。
LCT 后第 14 天至第 56 天，Pox 从移植前的 104.3±8.4μmol/L 下降至 70.0±15.0μmol/L。与 LCT 前（103.8μmol/L）和 LCT 后第 14 天至 LKTx （77.3μmol/L）之间的平均水平相比，Pox 显著持续降低（P<0.001），尽管 Pox 也出现了二次升高和更宽的范围。与此同时，患者的临床状况显著改善，在 LCT 后 12 个月，该女婴接受了尸体 LKTx。然而，从移植肝中取出的活检标本通过 amelogenin 聚合酶链反应未显示出男性供体细胞。
谨慎起见，我们的初步数据表明，LCT 在婴儿期草酸中毒中值得进一步研究。为了开发一种可以辅助治疗 PHI 的方法，显然需要改进方案和方法。
