Heidelberg University, Medical Faculty Heidelberg, and Center for Pediatric and Adolescent Medicine, Department I, Division of Pediatric Neurology and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
Heidelberg University, Medical Faculty Heidelberg, and Center for Pediatric and Adolescent Medicine, Department I, Division of Pediatric Neurology and Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
Mol Genet Metab. 2024 Sep-Oct;143(1-2):108566. doi: 10.1016/j.ymgme.2024.108566. Epub 2024 Aug 19.
In individuals with urea cycle disorders (UCDs) and neonatal disease onset, extracorporeal detoxification by continuous kidney replacement therapy is considered the therapeutic method of choice in addition to metabolic emergency treatment to resolve hyperammonemic decompensation. However, the indications for the initiation of dialysis are heterogeneously implemented transnationally, thereby hampering our understanding of (optimal) short-term health outcomes.
We performed a retrospective comparative analysis evaluating the therapeutic effects of initial dialysis on survival as well as neurocognitive outcome parameters in individuals with UCDs in comparison to a severity-adjusted non-dialyzed control cohort. Overall, 108 individuals with a severe phenotype of male ornithine transcarbamylase deficiency (mOTC-D), citrullinemia type 1 (CTLN1) and argininosuccinic aciduria (ASA) were investigated by stratification based on a recently established and validated genotype-specific disease prediction model.
Mortality is associated with the height of initial peak plasma ammonium concentration, but appears to be independent from treatment with initial dialysis in mOTC-D. However, improved survival after initial dialysis was observed in CTLN1, while there was a trend towards improved survival in ASA. In survivors, annual frequency of (subsequent) metabolic decompensations did not differ between the dialyzed and non-dialyzed cohorts. Moreover, treatment with initial dialysis was not associated with improved neurocognitive outcomes.
The present severity-adjusted comparative analysis reveals that general practice of initial dialysis is neither associated with improved survival in individuals with mOTC-D nor does it differ with regard to the neurocognitive outcome for the investigated UCD subtypes. However, initial dialysis might potentially prove beneficial for survival in CTLN1 and ASA.
The UCDC database is recorded at the US National Library of Medicine (https://clinicaltrials.gov).
在尿素循环障碍（UCD）患者和新生儿发病患者中，除代谢急症治疗以解决高氨血症性失代偿外，连续肾脏替代治疗的体外解毒被认为是首选的治疗方法。然而，起始透析的指征在国际上存在异质性实施，从而阻碍了我们对（最佳）短期健康结果的理解。
我们进行了回顾性比较分析，评估了初始透析对男性鸟氨酸氨甲酰基转移酶缺乏症（mOTC-D）、瓜氨酸血症 1 型（CTLN1）和精氨酸琥珀酸尿症（ASA）严重表型个体的生存和神经认知预后参数的治疗效果，与经过严重程度调整的未透析对照组进行比较。总体而言，通过基于最近建立和验证的基因型特异性疾病预测模型进行分层，研究了 108 名具有严重表型的个体。
死亡率与初始血浆铵峰浓度的高度相关，但在 mOTC-D 中似乎与初始透析治疗无关。然而，在 CTLN1 中观察到初始透析后生存率提高，而 ASA 中则存在生存率提高的趋势。在幸存者中，透析和未透析队列之间的（随后）代谢失代偿的年度频率没有差异。此外，初始透析治疗与神经认知结局的改善无关。
本严重程度调整的比较分析表明，初始透析的常规应用既不能改善 mOTC-D 患者的生存率，也不能改善所研究的 UCD 亚型的神经认知结局。然而，初始透析可能对 CTLN1 和 ASA 的生存有益。
UCDC 数据库在美国国家医学图书馆（https://clinicaltrials.gov）注册。
