Normoalbuminuric and albuminuric pathways to renal insufficiency in type 2 diabetes

多达三分之一的2型糖尿病患者会发生肾脏疾病（糖尿病肾病）。尿中蛋白质排泄增加（蛋白尿）通常是肾脏疾病的第一个征兆。蛋白尿通常从正常水平发展到中间阶段（微量蛋白尿），持续5-10年，然后出现明显的肾病（大量蛋白尿）。传统上认为，以肾小球滤过率来衡量的肾功能下降是伴随糖尿病肾病发展的。然而，我们小组最近的研究表明，大约四分之一的2型糖尿病患者肾功能受损，但蛋白尿没有增加。这提高了在2型糖尿病患者亚组中另一种非蛋白尿途径导致肾脏疾病的可能性。该研究将比较2型糖尿病和肾功能受损患者的肾脏结构和功能，这些患者是否伴有蛋白尿增加。这项比较将伴随着5年或更长时间内的肾功能下降率的测量，在有或没有蛋白尿增加的受试者中，以确认肾功能的下降可能独立于蛋白尿。肾损伤的替代机制的论证有可能为2型糖尿病患者肾脏疾病的治疗确定新的靶点。

Up to one third of patients with type 2 diabetes develop kidney disease (diabetic nephropathy). An increase in protein excretion in the urine (albuminuria) is usually the first sign of kidney disease. Albuminuria usually progresses from normal levels to an intermediate phase (microalbuminuria) lasting 5-10 years and is then followed by overt nephropathy (macroalbuminuria). It has been traditionally believed that onset of a decline in kidney function, measured as glomerular filtration rate, accompanies the development of diabetic kidney disease. However, recent studies by our group have shown that about one quarter of patients with type 2 diabetes have impaired kidney function without an increase in albuminuria. This raises the possibility that an alternate non-albuminuric pathway leads to kidney disease in a subgroup of patients with type 2 diabetes. This study will compare kidney structure and function in patients with type 2 diabetes and impaired kidney function with or without increases in albuminuria. The comparison will be accompanied by measurements of the rate of decline in kidney function over 5 years or more, in subjects with or without increases in albuminuria in order to confirm that kidney function may decline independently of albuminuria. The demonstration of alternate mechanisms of renal injury has the potential to identify new targets for the treatment of kidney disease in patients with type 2 diabetes.