血浆和尿液2,8-二羟基腺嘌呤和腺嘌呤与腺嘌呤磷酸核糖基转移酶缺乏症患者临床特征的相关性

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Unnur A. Thorsteinsdottir, Hrafnhildur L. Runolfsdottir, Vidar O. Edvardsson, Margret Thorsteinsdottir, Runolfur Palsson
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引用次数: 0

摘要

腺嘌呤磷酸核糖基转移酶(APRT)缺乏症是一种罕见的常染色体隐性遗传病,其特征是尿中排泄难溶性2,8-二羟基腺嘌呤(DHA),导致肾结石和慢性肾脏疾病。用黄嘌呤氧化还原酶(XOR)抑制剂别嘌呤醇和非布司他治疗可减少DHA的产生。采用超高效液相色谱-串联质谱法对26例APRT缺乏症患者的122对血浆和尿液样本进行DHA和腺嘌呤测定。采用Spearman等级相关法对23人87对血浆和尿液样本进行分析,评估血浆DHA和腺嘌呤浓度、尿DHA/肌酐(DHA/Cr)和腺嘌呤/肌酐(腺嘌呤/Cr)比值、年龄和肾小球滤过率(eGFR)之间的关系。别嘌呤醇和非布司他治疗降低了血浆DHA,中位(范围)浓度从未治疗个体的249 (123-1315)ng/mL下降到接受高剂量治疗个体的检测极限以下。XOR抑制剂治疗期间血浆腺嘌呤增加。在未经治疗的个体中,血浆DHA和eGFR之间存在很强的负相关(rs = - 0.74, p < 0.0001)。在接受别嘌呤醇或非布司他治疗的个体中,血浆DHA与尿DHA/Cr比值相关(rs = 0.65, p < 0.0001),而在未接受治疗的个体中,没有观察到显著相关性(rs = - 0.26, p = 0.14)。用XOR抑制剂治疗可有效降低DHA的血浆浓度和尿排泄。血浆DHA和eGFR之间有很强的相关性,而未经治疗的个体血浆DHA和尿DHA/Cr比值之间缺乏相关性,这表明血浆DHA可能是一个更可靠的全身DHA负荷指标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Correlation of Plasma and Urine 2,8-Dihydroxyadenine and Adenine and Clinical Characteristics in Individuals With Adenine Phosphoribosyltransferase Deficiency

Adenine phosphoribosyltransferase (APRT) deficiency is a rare, autosomal recessive disorder characterized by urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. Treatment with the xanthine oxidoreductase (XOR) inhibitors allopurinol and febuxostat reduces DHA production. DHA and adenine were measured in 122 paired plasma and urine samples from 26 individuals with confirmed APRT deficiency, using ultra-performance liquid chromatography–tandem mass spectrometry assays. The relationship between plasma DHA and adenine concentrations, urine DHA-to-creatinine (DHA/Cr) and adenine-to-creatinine (adenine/Cr) ratios, and age and estimated glomerular filtration rate (eGFR) was evaluated in a subset of 87 paired plasma and urine samples from 23 individuals using Spearman's rank correlation. Allopurinol and febuxostat treatment reduced plasma DHA, with the median (range) concentration decreasing from 249 (123–1315) ng/mL in untreated individuals to below the limit of detection in those receiving higher doses. Plasma adenine increased during XOR inhibitor treatment. In untreated individuals, a strong negative correlation was observed between plasma DHA and eGFR (rs = −0.74, p < 0.0001). Plasma DHA correlated with urine DHA/Cr ratio in individuals treated with allopurinol or febuxostat (rs = 0.65, p < 0.0001), while no significant correlation was observed in untreated individuals (rs = −0.26, p = 0.14). Treatment with XOR inhibitors effectively reduces the plasma concentration and urinary excretion of DHA. The strong correlation between plasma DHA and eGFR, combined with the lack of correlation between plasma DHA and urine DHA/Cr ratio in untreated individuals, suggests that plasma DHA may be a more reliable marker of systemic DHA burden.

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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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