Liver Transplantation Center Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83303, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.
Orphanet J Rare Dis. 2021 Oct 11;16(1):423. doi: 10.1186/s13023-021-02026-6.
Glycogen storage disease type I (GSD-I) is an autosomal recessive disorder of carbohydrate metabolism, resulting in limited production of glucose and excessive glycogen storage in the liver and kidneys. These patients are characterized by life-threatening hypoglycemia, metabolic derangements, hepatomegaly, chronic kidney disease, and failure to thrive. Liver transplantation (LT) has been performed for poor metabolic control and delayed growth. However, renal outcome was diverse in pediatric GSD patients after LT. The aim of this study was to investigate the long-term outcome of renal function in pediatric GSD-I patients after living donor LT (LDLT), and to identify modifiable variables that potentially permits LT to confer native renal preservation.
The study included eight GSD-Ia and one GSD-Ib children with a median age of 9.0 (range 4.2-15.7) years at the time of LT. Using propensity score matching, 20 children with biliary atresia (BA) receiving LT were selected as the control group by matching for age, sex, pre-operative serum creatinine (SCr) and pediatric end-stage liver disease (PELD) score. Renal function was evaluated based on the SCr, estimated glomerular filtration rate (eGFR), microalbuminuria, and morphological changes in the kidneys. Comparability in long-term renal outcome in terms of anatomic and functional parameters will help to identify pre-LT factors of GSD-I that affect renal prognosis.
The clinical and biochemical characteristics of the GSD and BA groups were similar, including immunosuppressive regimens and duration of follow-up (median 15 years) after LT. Overall, renal function, including eGFR and microalbuminuria was comparable in the GSD-I and BA groups (median eGFR: 111 vs. 123 ml/min/1.73m, P = 0.268; median urine microalbuminuria to creatinine ratio: 16.0 vs. 7.2 mg/g, P = 0.099, respectively) after LT. However, in the subgroups of the GSD cohort, patients starting cornstarch therapy at an older age (≥ 6-year-old) before transplantation demonstrated a worse renal outcome in terms of eGFR change over years (P < 0.001). In addition, the enlarged kidney in GSD-I returned to within normal range after LT.
Post-LT renal function was well-preserved in most GSD-I patients. Early initiation of cornstarch therapy before preschool age, followed by LT, achieved a good renal prognosis.
糖原贮积病 I 型（GSD-I）是一种碳水化合物代谢的常染色体隐性遗传病，导致葡萄糖产生受限和肝脏、肾脏中糖原过度储存。这些患者的特征是危及生命的低血糖、代谢紊乱、肝肿大、慢性肾脏病和生长迟缓。肝移植（LT）已用于代谢控制不良和生长迟缓的患者。然而，儿科 GSD 患者 LT 后的肾脏结局存在差异。本研究旨在探讨儿童 GSD-I 患者接受活体供者 LT（LDLT）后的肾脏功能长期结局，并确定潜在的可改变变量，使 LT 能够实现对固有肾脏的保护。
本研究纳入了 8 例 GSD-Ia 型和 1 例 GSD-Ib 型患者，LT 时的中位年龄为 9.0 岁（范围 4.2-15.7 岁）。通过倾向评分匹配，选择 20 例接受 LT 的胆道闭锁（BA）患儿作为对照组，匹配年龄、性别、术前血肌酐（SCr）和小儿终末期肝病评分（PELD）。根据 SCr、估算肾小球滤过率（eGFR）、微量白蛋白尿和肾脏形态学改变评估肾脏功能。LT 前 GSD-I 的解剖和功能参数的长期肾脏结局的可比性有助于确定影响肾脏预后的 GSD-I 因素。
GSD 和 BA 组的临床和生化特征相似，包括免疫抑制方案和 LT 后的随访时间（中位数 15 年）。总体而言，LT 后 GSD-I 和 BA 组的肾功能（包括 eGFR 和微量白蛋白尿）相当（中位 eGFR：111 与 123 ml/min/1.73m，P=0.268；中位尿微量白蛋白尿与肌酐比值：16.0 与 7.2 mg/g，P=0.099）。然而，在 GSD 队列的亚组中，移植前年龄较大（≥6 岁）开始使用玉米淀粉治疗的患者，其 eGFR 随时间的变化显示出更差的肾脏结局（P<0.001）。此外，GSD-I 的增大肾脏在 LT 后恢复到正常范围。
大多数 GSD-I 患者 LT 后的肾脏功能得到良好保存。学龄前早期开始玉米淀粉治疗，随后进行 LT，可获得良好的肾脏预后。
