Department of Pediatrics, University of Chieti, Via dei Vestini 5, 66100, Chieti, Italy.
Pediatr Nephrol. 2012 Feb;27(2):269-75. doi: 10.1007/s00467-011-1988-5. Epub 2011 Aug 26.
The advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We evaluated endogenous secretory (es)RAGE and soluble (s)RAGE concentrations in 64 pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and compared the values with those of 62 controls matched for age, gender and Tanner pubertal stages. We also explored the possible association of their concentrations with early signs of diabetic nephropathy, defined as changes in kidney volume and estimated glomerular filtration rate (eGFR). Significantly lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal (p = 0.003 and p = 0.001) and pubertal (p = 0.002 and p = 0.001) subjects with type 1 diabetes than in the controls. In both groups of patients with type 1 diabetes, the eGFR (pre-pubertal p = 0.01 and pubertal p = 0.01) and the mean value of kidney volume adjusted for body surface (pre-pubertal p = 0.003 and pubertal p = 0.002) were higher than those of the controls. The regression analysis showed an inverse relationship between esRAGE and body surface-adjusted mean kidney volume (p = 0.0004, r = -0.503). esRAGE and sRAGE concentrations were lower in normoalbuminuric youths with type 1 diabetes than in their healthy peers. The inverse association between esRAGE levels and early kidney alterations suggests a potential role of esRAGE in diabetic nephropathy.
糖基化终产物/糖基化终产物受体（AGE-RAGE）通路是 1 型糖尿病肾小球改变的关键介质。我们评估了 64 名青春期前和青春期的 1 型糖尿病伴正常白蛋白尿患者的内源性分泌型（es）RAGE 和可溶性（s）RAGE 浓度，并将这些值与 62 名年龄、性别和 Tanner 青春期阶段匹配的对照者进行比较。我们还探讨了它们的浓度与糖尿病肾病早期标志物（定义为肾脏体积和估算肾小球滤过率（eGFR）的变化）的可能关联。与对照组相比，1 型糖尿病的青春期前（p=0.003 和 p=0.001）和青春期（p=0.002 和 p=0.001）患者的 esRAGE 和 sRAGE 浓度均显著降低。在 1 型糖尿病的两组患者中，eGFR（青春期前 p=0.01 和青春期 p=0.01）和按体表面积校正的肾脏体积平均值（青春期前 p=0.003 和青春期 p=0.002）均高于对照组。回归分析显示，esRAGE 与按体表面积校正的平均肾脏体积呈负相关（p=0.0004，r=-0.503）。1 型糖尿病的正常白蛋白尿青少年的 esRAGE 和 sRAGE 浓度低于其健康同龄人。esRAGE 水平与早期肾脏改变之间的负相关提示 esRAGE 在糖尿病肾病中的潜在作用。
