López de Heredia Miguel, Muñoz Lourdes, Carru Ciriaco, Sotgia Salvatore, Zinellu Angelo, Serra Carmen, Llebaria Amadeu, Kato Yukio, Nunes Virginia
Human Molecular Genetics Laboratory, Gene, Disease and Therapy Program, IDIBELL, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)-CB06/07/0069, Instituto de Salud Carlos III, 28029 Madrid, Spain.
Antioxidants (Basel). 2021 Sep 7;10(9):1424. doi: 10.3390/antiox10091424.
Cystinuria, a rare inherited aminoaciduria condition, is characterized by the hyperexcretion of cystine, ornithine, lysine, and arginine. Its main clinical manifestation is cystine stone formation in the urinary tract, being responsible for 1-2% total and 6-8% pediatric lithiasis. Cystinuria patients suffer from recurrent lithiasic episodes that might end in surgical interventions, progressive renal functional deterioration, and kidney loss. Cystinuria is monitored for the presence of urinary cystine stones by crystalluria, imaging techniques or urinary cystine capacity; all with limited predicting capabilities. We analyzed blood and urine levels of the natural antioxidant L-ergothioneine in a Type B cystinuria mouse model, and urine levels of its metabolic product S-methyl-L-ergothioneine, in both male and female mice at two different ages and with different lithiasic phenotype. Urinary levels of S-methyl-L-ergothioneine showed differences related to age, gender and lithiasic phenotype. Once normalized by L-ergothioneine to account for interindividual differences, the S-methyl-L-ergothioneine to L-ergothioneine urinary ratio discriminated between cystine lithiasic phenotypes. Urine S-methyl-L-ergothioneine to L-ergothioneine ratio could be easily determined in urine and, as being capable of discriminating between cystine lithiasis phenotypes, it could be used as a lithiasis biomarker in cystinuria patient management.
胱氨酸尿症是一种罕见的遗传性氨基酸尿症，其特征是胱氨酸、鸟氨酸、赖氨酸和精氨酸排泄过多。其主要临床表现是尿路胱氨酸结石形成，占全部结石的1%-2%，儿童结石的6%-8%。胱氨酸尿症患者会反复出现结石发作，最终可能需要手术干预、肾功能进行性恶化以及肾脏丧失。通过结晶尿、成像技术或尿胱氨酸容量监测胱氨酸尿症患者是否存在尿胱氨酸结石；但这些方法的预测能力都有限。我们分析了B型胱氨酸尿症小鼠模型中天然抗氧化剂L-麦角硫因的血液和尿液水平，以及其代谢产物S-甲基-L-麦角硫因在两个不同年龄、具有不同结石表型的雄性和雌性小鼠中的尿液水平。S-甲基-L-麦角硫因的尿液水平显示出与年龄、性别和结石表型相关的差异。一旦用L-麦角硫因进行标准化以考虑个体差异，S-甲基-L-麦角硫因与L-麦角硫因的尿比值就能区分胱氨酸结石表型。尿中S-甲基-L-麦角硫因与L-麦角硫因的比值可以很容易地在尿液中测定，并且由于能够区分胱氨酸结石表型，它可以用作胱氨酸尿症患者管理中的结石生物标志物。
