Trial reportMolecular genetics and metabolism2012
A randomized controlled trial to evaluate the effects of high-dose versus low-dose of arginine therapy on hepatic function tests in argininosuccinic aciduria.
Trial report in Molecular genetics and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- Biomarkers for liver disease in urea cycle disorders.Molecular genetics and metabolism · 2021Trial
- Argininosuccinate Lyase Deficiency Causes an Endothelial-Dependent Form of Hypertension.American journal of human genetics · 2018Trial
- Dysregulation of the urea cycle - potential targets for treatment and diagnosis in prostate cancer.Expert reviews in molecular medicine · 2026Review
- Current Treatment Modalities for Urea Cycle Disorders.Paediatric drugs · 2025Review
- Clinical, biochemical and genetic characteristics of patients with argininosuccinate lyase deficiency from a single center cohort in China.Orphanet journal of rare diseases · 2025Article
- Prevalence of fibrosis in hepatic explants and biopsies from individuals with urea cycle disorders.Molecular genetics and metabolism · 2025Article
- Genetic and functional correction of argininosuccinate lyase deficiency using CRISPR adenine base editors.American journal of human genetics · 2024Article
- mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aciduria.Science translational medicine · 2024Article
- Treatment and management for children with urea cycle disorder in chronic stage.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Article
- Chronic liver disease and impaired hepatic glycogen metabolism in argininosuccinate lyase deficiency.JCI insight · 2020Article
- Untargeted metabolomic profiling reveals multiple pathway perturbations and new clinical biomarkers in urea cycle disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders-A successful strategy for clinical research of rare diseases.Journal of inherited metabolic disease · 2019Article
- Low prevalence of argininosuccinate lyase deficiency among inherited urea cycle disorders in Korea.Journal of human genetics · 2018Article
- The intestinal-renal axis for arginine synthesis is present and functional in the neonatal pig.American journal of physiology. Endocrinology and metabolism · 2017Article
- Interrelationships between glutamine and citrulline metabolism.Current opinion in clinical nutrition and metabolic care · 2016Review
- The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype.Journal of inherited metabolic disease · 2015Article
- Inherited Metabolic Disorders: Aspects of Chronic Nutrition Management.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2015Review
- Metabolic dysregulation in monogenic disorders and cancer - finding method in madness.Nature reviews. Cancer · 2015Review
- A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.Clinical genetics · 2015Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveTo compare the effects of combinatorial therapy with low-dose arginine and a nitrogen scavenging agent (sodium phenylbutyrate) vs. monotherapy with high-dose arginine on liver function tests in patients with argininosuccinic aciduria (ASA). STUDY
designTwelve patients with ASA were enrolled in a double-blind, placebo-controlled, cross-over study design. Subjects were randomized to receive either a low-dose of arginine therapy (100 mg · kg(-1) · d(-1)) combined with sodium phenylbutyrate (500 mg · kg(-1) · d(-1)) (LDA arm) or a high-dose of arginine alone (500 mg · kg(-1) · d(-1)) (HDA arm) for one week. At the end of one week of therapy, liver function tests were assessed and metabolite fluxes were measured using a multi-tracer stable isotope protocol.
resultsPlasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and measures of synthetic functions of the liver were the primary outcomes. Subjects had significantly increased levels of argininosuccinate (P<0.03) and AST levels (P<0.01) after treatment with high-dose arginine. In the subset of subjects with elevated AST or ALT, treatment with high-dose of arginine was associated with further increases in plasma levels of both aminotransferases. Whereas subjects had increased arginine and citrulline flux with high-dose arginine therapy, the glutamine flux was not different between the two treatment arms. The synthetic liver functions as assessed by prothrombin time, INR, and coagulation factor levels were not different between the HDA and LDA arms.
conclusionsAdministering higher doses of arginine in subjects with ASA results in increases in AST and ALT levels, especially in the subset of patients with elevated baseline aminotransferases. Hence, low-dose arginine sufficient to normalize arginine levels in plasma combined with nitrogen scavenging therapy should be considered as a therapeutic option for treatment of ASA in patients with elevations of hepatic aminotransferases.
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