法布里病中维生素 C 的尿丢失：维生素 C 肾漏的临床和基因组特征。

Vitamin C Urinary Loss in Fabry Disease: Clinical and Genomic Characteristics of Vitamin C Renal Leak.

机构信息

Molecular and Clinical Nutrition Section, Digestive Diseases Branch, Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health, Bethesda, MD, USA.

出版信息

J Nutr. 2023 Jul;153(7):1994-2003. doi: 10.1016/j.tjnut.2022.12.009. Epub 2023 Mar 10.

DOI:10.1016/j.tjnut.2022.12.009

PMID:37229630

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10375496/

Abstract

BACKGROUND

Reduced plasma vitamin C concentrations in chronic diseases may result from abnormal urinary excretion of vitamin C: a renal leak. We hypothesized that vitamin C renal leak may be associated with disease-mediated renal dysregulation, resulting in aberrant vitamin C renal reabsorption and increased urinary loss.

OBJECTIVES

We investigated the prevalence, clinical characteristics, and genomic associations of vitamin C renal leak in Fabry disease, an X-linked lysosomal disease associated with renal tubular dysfunction and low plasma vitamin C concentrations.

METHODS

We conducted a non-randomized cross-sectional cohort study of men aged 24-42 y, with Fabry disease (n = 34) and controls without acute or chronic disease (n = 33). To match anticipated plasma vitamin C concentrations, controls were placed on a low-vitamin C diet 3 wk before inpatient admission. To determine the primary outcome of vitamin C renal leak prevalence, subjects were fasted overnight, and matched urine and fasting plasma vitamin C measurements were obtained the following morning. Vitamin C renal leak was defined as presence of urinary vitamin C at plasma concentrations below 38 μM. Exploratory outcomes assessed the association between renal leak and clinical parameters, and genomic associations with renal leak using single nucleotide polymorphisms (SNPs) in the vitamin C transporter SLC23A1.

RESULTS

Compared with controls, the Fabry cohort had 16-fold higher odds of renal leak (6% vs. 52%; OR: 16; 95% CI: 3.30, 162; P < 0.001). Renal leak was associated with higher protein creatinine ratio (P < 0.01) and lower hemoglobin (P = 0.002), but not estimated glomerular filtration rate (P = 0.54). Renal leak, but not plasma vitamin C, was associated with a nonsynonymous single nucleotide polymorphism in vitamin C transporter SLC23A1 (OR: 15; 95% CI: 1.6, 777; P = 0.01).

CONCLUSIONS

Increased prevalence of renal leak in adult men with Fabry disease may result from dysregulated vitamin C renal physiology and is associated with abnormal clinical outcomes and genomic variation.

摘要

背景

慢性疾病患者血浆维生素 C 浓度降低可能是由于维生素 C 的异常尿排泄：肾脏漏出。我们假设维生素 C 肾脏漏出可能与疾病介导的肾脏失调有关，导致异常的维生素 C 肾脏重吸收和增加的尿丢失。

目的

我们研究了法布里病（一种与肾小管功能障碍和低血浆维生素 C 浓度相关的 X 连锁溶酶体疾病）中维生素 C 肾脏漏出的患病率、临床特征和基因组关联。

方法

我们进行了一项非随机横断面队列研究，纳入了 24-42 岁的男性，其中包括法布里病患者（n=34）和无急性或慢性疾病的对照者（n=33）。为了匹配预期的血浆维生素 C 浓度，对照者在住院前 3 周接受低维生素 C 饮食。为了确定维生素 C 肾脏漏出的患病率这一主要结局，研究对象在夜间禁食，次日清晨采集匹配的尿液和空腹血浆维生素 C 测量值。将尿维生素 C 存在于血浆浓度低于 38 μM 的情况定义为肾脏漏出。探索性结局评估了肾脏漏出与临床参数之间的关联，以及使用维生素 C 转运体 SLC23A1 中的单核苷酸多态性（SNP）与肾脏漏出的基因组关联。

结果

与对照者相比，法布里病队列的肾脏漏出的几率高 16 倍（6%比 52%；比值比：16；95%可信区间：3.30，162；P<0.001）。肾脏漏出与更高的蛋白肌酐比（P<0.01）和更低的血红蛋白（P=0.002）相关，但与估算的肾小球滤过率（P=0.54）无关。肾脏漏出，但不是血浆维生素 C，与维生素 C 转运体 SLC23A1 中的非同义单核苷酸多态性相关（比值比：15；95%可信区间：1.6，777；P=0.01）。