Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Centre of Biomedical Research, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Lupus. 2020 Jun;29(7):782-786. doi: 10.1177/0961203320918011. Epub 2020 Apr 16.
Metabolomics, the study of global alterations in small metabolites, is a useful tool to look for novel biomarkers. Recently, we reported a reprogramming of the serum metabolomic profile by nuclear magnetic resonance (NMR) spectroscopy following treatment in lupus nephritis (LN). This study aimed to compare the urine excretory levels of citrate and acetate in patients with biopsy-proven LN before and six months after cyclophosphamide induction therapy and to evaluate their correlation with the Systemic Lupus Erythematosus Disease Activity Index 2K (SLEDAI 2K) and renal SLEDAI.
Urine obtained from LN patients ( = 18, 16 female) at diagnosis and six months following induction therapy with cyclophosphamide and healthy controls (HC; = 18, median age = 35 years, all female) were stored at -80°C. Metabolomic profiling was done using high resolution 800 MHz 1D H NMR spectroscopy. The urinary ratio of metabolites was calculated as (metabolite×1000)/creatinine. Disease activity was measured using the SLEDAI. Metabolomic profiles were compared between groups and correlated with clinical parameters.
Compared to HC, LN patients had significantly lower median urinary citrate/creatinine levels (LN = 18.26, range 12.80-27.62; HC = 107.7, range 65.39-138.4; < 0.0001) which significantly increased after six months of cyclophosphamide treatment (51.05, range 11.51-170.2; = 0.03). LN patients also differed from HC by having a higher mean urinary acetate/creatinine ratio (LN = 17.44, range 11.6-32.7; HC = 9.61, range 7.97-13.71; = 0.054) with a non-significant fall in values after six months of treatment. The Area under curve for differentiating LN from HC for urinary citrate was 0.9136, and urinary acetate was 0.6883. The urinary acetate levels correlated with SLEDAI ( = 0.337, = 0.048). Urinary citrate levels correlated positively with C3 ( = 0.362, = 0.03) and negatively with urine protein/creatinine ( = -0.346, = 0.039).
Urinary citrate, which reflects dampened aerobic glycolysis and oxidative phosphorylation, improved significantly and is a potential non-invasive biomarker for diagnosis and monitoring treatment response in LN.
代谢组学是研究小分子代谢物整体变化的一种方法，可用于寻找新的生物标志物。最近，我们通过核磁共振（NMR）光谱报告了狼疮肾炎（LN）治疗后血清代谢组谱的重编程。本研究旨在比较经活检证实的 LN 患者在环磷酰胺诱导治疗前和治疗后 6 个月的尿排泄柠檬酸和乙酸水平，并评估其与系统性红斑狼疮疾病活动指数 2K（SLEDAI 2K）和肾脏 SLEDAI 的相关性。
LN 患者（n=18，16 名女性）在诊断时和环磷酰胺诱导治疗后 6 个月收集尿液，并与健康对照组（HC；n=18，中位年龄 35 岁，均为女性）储存于-80°C。使用高分辨率 800 MHz 1D H NMR 光谱进行代谢组学分析。代谢物的尿比由（代谢物×1000）/肌酐计算得出。采用 SLEDAI 评估疾病活动度。比较组间代谢组学谱，并与临床参数相关。
与 HC 相比，LN 患者的中位尿柠檬酸/肌酐水平明显降低（LN=18.26，范围 12.80-27.62；HC=107.7，范围 65.39-138.4； <0.0001），经环磷酰胺治疗 6 个月后明显升高（51.05，范围 11.51-170.2； = 0.03）。LN 患者的尿乙酸/肌酐比值也明显高于 HC（LN=17.44，范围 11.6-32.7；HC=9.61，范围 7.97-13.71； = 0.054），但治疗 6 个月后无显著下降。尿柠檬酸鉴别 LN 与 HC 的曲线下面积为 0.9136，尿乙酸为 0.6883。尿乙酸水平与 SLEDAI 相关（ = 0.337， = 0.048）。尿柠檬酸水平与 C3 呈正相关（ = 0.362， = 0.03），与尿蛋白/肌酐呈负相关（ = -0.346， = 0.039）。
反映有氧糖酵解和氧化磷酸化减弱的尿柠檬酸显著改善，是诊断和监测 LN 治疗反应的潜在非侵入性生物标志物。
