Piechowicz Joanna, Gamian Andrzej, Chukwu Ositadima, Polak-Jonkisz Dorota
Department of Medical Biochemistry, Wroclaw Medical University, 50-367 Wroclaw, Poland.
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 50-367 Wroclaw, Poland.
Curr Issues Mol Biol. 2022 Aug 7;44(8):3518-3532. doi: 10.3390/cimb44080242.
Nitric oxide (NO) is an important signaling molecule for many physiological and pathological processes. Diseases associated with abnormal NO synthesis include cardiovascular diseases, insulin-dependent diabetes, or chronic kidney disease (CKD). The aim of the paper was to evaluate NO synthesis metabolites, i.e., asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), dimethylamine (DMA), arginine, citrulline in plasma of patients with different severity of CKD and to seek possible links between these parameters and the development of this disease. Forty-eight CKD children and thirty-three age-matched controls were examined. Patients were divided into groups depending on the CKD stages (Group II-stage II, Group III-stage III, Group IV-stage IV, and Group RRT children on dialysis). To determine the concentrations of the above-mentioned metabolites in plasma liquid chromatography-mass spectrometry was used. There were significant differences observed in levels of ADMA, SDMA, DMA, and citrulline between control vis CKD groups (p values ranging from <0.001 to 0.029). Plasma arginine concentration was also higher in CKD patients compared to the control group but statistically insignificant. ADMA levels in CKD children were statistically significantly higher in relation to particular stages of CKD (RRT vis II stage of CKD: p = 0.01; RRT vis III-IV stages of CKD: p < 0.046). Citrulline levels in CKD children were statistically significantly higher in RRT group vis control (p < 0.001). Children with CKD develop disturbances in most metabolites of NO synthesis. Dialysis children treated show the greatest disturbances of plasma ADMA and citrulline levels. ADMA seems to be a good indicator of the gradual progression of the CKD, which is proved by the negative correlation with eGFR.
一氧化氮（NO）是许多生理和病理过程中的重要信号分子。与NO合成异常相关的疾病包括心血管疾病、胰岛素依赖型糖尿病或慢性肾脏病（CKD）。本文的目的是评估不同严重程度CKD患者血浆中NO合成代谢产物，即不对称二甲基精氨酸（ADMA）、对称二甲基精氨酸（SDMA）、二甲胺（DMA）、精氨酸、瓜氨酸，并寻找这些参数与该疾病发展之间的可能联系。对48名CKD儿童和33名年龄匹配的对照者进行了检查。根据CKD分期将患者分为几组（II组——II期，III组——III期，IV组——IV期，RRT组——接受透析的儿童）。采用液相色谱-质谱法测定上述代谢产物在血浆中的浓度。在对照组和CKD组之间观察到ADMA、SDMA、DMA和瓜氨酸水平存在显著差异（p值范围为<0.001至0.029）。与对照组相比，CKD患者的血浆精氨酸浓度也更高，但无统计学意义。CKD儿童的ADMA水平相对于CKD的特定阶段在统计学上显著更高（RRT组与CKD II期相比：p = 0.01；RRT组与CKD III-IV期相比：p < 0.046）。与对照组相比，RRT组CKD儿童的瓜氨酸水平在统计学上显著更高（p < 0.001）。CKD儿童的大多数NO合成代谢产物出现紊乱。接受透析治疗的儿童血浆ADMA和瓜氨酸水平的紊乱最为严重。ADMA似乎是CKD逐渐进展的良好指标，这一点通过与估算肾小球滤过率（eGFR）的负相关得到证实。
