Petrica Ligia, Vlad Adrian, Gluhovschi Gheorghe, Gadalean Florica, Dumitrascu Victor, Gluhovschi Cristina, Velciov Silvia, Bob Flaviu, Vlad Daliborca, Popescu Roxana, Milas Oana, Ursoniu Sorin
"Victor Babes" University of Medicine and Pharmacy, Dept. of Nephrology, Timisoara, Romania; County Emergency Hospital, Timisoara, Romania.
"Victor Babes" University of Medicine and Pharmacy, Dept. of Diabetes and Metabolic Diseases, Timisoara, Romania; County Emergency Hospital, Timisoara, Romania.
PLoS One. 2014 Nov 14;9(11):e112538. doi: 10.1371/journal.pone.0112538. eCollection 2014.
There is an ongoing debate as to whether early diabetic nephropathy in Type 2 diabetes mellitus may be attributed to the glomerulus or to the proximal tubule. Urinary excretion of nephrin and vascular endothelial growth factor may increase even in the normoalbuminuria stage. In the course of diabetic nephropathy, the proximal tubule may be involved in the uptake of urinary nephrin and vascular endothelial growth factor.
Two groups of consecutive Type 2 diabetes mellitus outpatients (38 normo-, 32 microalbuminuric) and 21 healthy subjects were enrolled in a cross-sectional study and evaluated concerning the relation of proximal tubule dysfunction with the podocyte biomarkers excretion, assessed by ELISA methods. The impact of advanced glycation end-products on this relation was also queried.
Urinary alpha1-microglobulin and kidney injury molecule-1 correlated with urinary albumin:creatinine ratio (R2 = 0.269; p < 0.001; R2 = 0.125; p < 0.001), nephrinuria (R2 = 0.529; p<0.001; R2 = 0.203; p < 0.001), urinary vascular endothelial growth factor (R2 = 0.709; p < 0.001; R2 = 0.360; p < 0.001), urinary advanced glycation end-products (R2 = 0.578; p < 0.001; R2 = 0.405; p < 0.001), serum cystatin C (R2 = 0.130; p < 0.001; R2 = 0.128; p<0.001), and glomerular filtration rate (R2 = 0.167; p < 0.001; R2 = 0.166; p < 0.001); nephrinuria and urinary vascular endothelial growth factor correlated with urinary albumin:creatinine ratio (R2 = 0.498; p < 0.001; R2 = 0.227; p<0.001), urinary advanced glycation end-products (R2 = 0.251; p < 0.001; R2 = 0.308; p < 0.001), serum cystatin C (R2 = 0.157; p < 0.001; R2 = 0.226; p < 0.001), and glomerular filtration rate (R2 = 0.087; p = 0.007; R2 = 0.218; p < 0.001).
In Type 2 diabetes mellitus there is an association of proximal tubule dysfunction with podocyte damage biomarkers, even in the normoalbuminuria stage. This observation suggests a potential role of the proximal tubule in urinary nephrin and urinary vascular endothelial growth factor processing in early diabetic nephropathy, a fact which could be related to advanced glycation end-products intervention. Podocyte damage and proximal tubule dysfunction biomarkers could be validated as a practical approach to the diagnosis of early diabetic nephropathy by further studies on larger cohorts.
关于2型糖尿病早期糖尿病肾病的病因是肾小球还是近端小管，目前仍存在争议。即使在正常白蛋白尿阶段，nephrin和血管内皮生长因子的尿排泄量也可能增加。在糖尿病肾病的病程中，近端小管可能参与了尿nephrin和血管内皮生长因子的摄取。
两组连续的2型糖尿病门诊患者（38例正常白蛋白尿者、32例微量白蛋白尿者）和21名健康受试者纳入一项横断面研究，通过ELISA方法评估近端小管功能障碍与足细胞生物标志物排泄之间的关系。同时也探讨了晚期糖基化终产物对这种关系的影响。
尿α1-微球蛋白和肾损伤分子-1与尿白蛋白：肌酐比值（R2 = 0.269；p < 0.001；R2 = 0.125；p < 0.001）、nephrinuria（R2 = 0.529；p<0.001；R2 = 0.203；p < 0.001）、尿血管内皮生长因子（R2 = 0.709；p < 0.001；R2 = 0.360；p < 0.001）、尿晚期糖基化终产物（R2 = 0.578；p < 0.001；R2 = 0.405；p < 0.001）、血清胱抑素C（R2 = 0.130；p < 0.001；R2 = 0.128；p<0.001）以及肾小球滤过率（R2 = 0.167；p < 0.001；R2 = 0.166；p < 0.001）相关；nephrinuria和尿血管内皮生长因子与尿白蛋白：肌酐比值（R2 = 0.498；p < 0.001；R2 = 0.227；p<0.001）、尿晚期糖基化终产物（R2 = 0.251；p < 0.001；R2 = 0.308；p < 0.001）、血清胱抑素C（R2 = 0.157；p < 0.001；R2 = 0.226；p < 0.001）以及肾小球滤过率（R2 = 0.087；p = 0.007；R2 = 0.218；p < 0.001）相关。
在2型糖尿病中，即使在正常白蛋白尿阶段，近端小管功能障碍也与足细胞损伤生物标志物相关。这一观察结果提示近端小管在早期糖尿病肾病尿nephrin和尿血管内皮生长因子处理过程中可能发挥潜在作用，这一事实可能与晚期糖基化终产物的干预有关。通过对更大队列的进一步研究，足细胞损伤和近端小管功能障碍生物标志物可作为早期糖尿病肾病诊断的实用方法得到验证。
