Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA.
Clinical Investigation Center CIC1402, CHU Poitiers, University of Poitiers, INSERM, Poitiers, France.
Metabolomics. 2018 Jun 8;14(6):84. doi: 10.1007/s11306-018-1380-6.
Little is known about the association of urine metabolites with structural lesions in persons with diabetes.
We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.
Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan, and included a kidney biopsy at the end of the treatment period. Metabolites were measured in urine samples collected within a median of 6.5 months before the research biopsy. Associations of the creatinine-adjusted urine metabolites with kidney structural variables were examined by Pearson's correlations and multivariable linear regression after adjustment for age, sex, diabetes duration, hemoglobin A, mean arterial pressure, glomerular filtration rate (iothalamate), and losartan treatment.
Participants (n = 62, mean age 45 ± 10 years) had mean ± standard deviation glomerular filtration rate of 137 ± 50 ml/min and median (interquartile range) urine albumin:creatinine ratio of 34 (14-85) mg/g near the time of the biopsy. Urine aconitic and glycolic acids correlated positively with glomerular filtration surface density (partial r = 0.29, P = 0.030 and r = 0.50, P < 0.001) and total filtration surface per glomerulus (partial r = 0.32, P = 0.019 and r = 0.43, P = 0.001). 2-ethyl 3-OH propionate correlated positively with the percentage of fenestrated endothelium (partial r = 0.32, P = 0.019). Citric acid correlated negatively with mesangial fractional volume (partial r=-0.36, P = 0.007), and homovanillic acid correlated negatively with podocyte foot process width (partial r=-0.31, P = 0.022).
Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.
关于尿液代谢物与糖尿病患者的结构损伤之间的关联，人们知之甚少。
我们研究了 12 种尿液代谢物与美国印第安人 2 型糖尿病患者肾脏结构之间的关系。
本研究数据来自一项为期 6 年的临床试验，评估了氯沙坦的肾保护疗效，并在治疗结束时进行了肾脏活检。在研究活检前中位数为 6.5 个月时收集尿液样本，以测量代谢物。通过 Pearson 相关分析和多变量线性回归，在调整年龄、性别、糖尿病病程、血红蛋白 A、平均动脉压、肾小球滤过率（碘海醇）和氯沙坦治疗后，研究了肌酐调整后的尿液代谢物与肾脏结构变量之间的相关性。
研究参与者（n=62，平均年龄 45±10 岁）的平均肾小球滤过率为 137±50ml/min，活检时尿液白蛋白/肌酐比值中位数（四分位间距）为 34（14-85）mg/g。尿液柠檬酸和乙二醇酸与肾小球滤过表面积密度呈正相关（偏相关系数分别为 0.29，P=0.030 和 r=0.50，P<0.001）和每个肾小球的总滤过表面积（偏相关系数分别为 0.32，P=0.019 和 r=0.43，P=0.001）。2-乙基-3-羟基丙酸与窗孔内皮的百分比呈正相关（偏相关系数为 0.32，P=0.019）。柠檬酸与系膜分数体积呈负相关（偏相关系数为-0.36，P=0.007），高香草酸与足细胞足突宽度呈负相关（偏相关系数为-0.31，P=0.022）。
尿液代谢物的改变可能与糖尿病肾病的早期肾小球病变有关。
