Normoalbuminuric and albuminuric pathways to renal insufficiency in type 2 diabetes

多达三分之一的2型糖尿病患者会患上肾脏疾病(糖尿病肾病)。尿蛋白排泄增加(蛋白尿)通常是肾脏疾病的第一个症状。蛋白尿通常从正常水平进展到中间阶段(微量蛋白尿)，持续5-10年，然后是临床肾病(大量蛋白尿)。传统上认为，随着糖尿病肾病的发展，肾功能下降(以肾小球滤过率衡量)的开始。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。这增加了一种可能性，即在一组2型糖尿病患者中，另一种非蛋白尿途径导致肾脏疾病。这项研究将比较伴有或不伴有蛋白尿增加的2型糖尿病患者和肾功能受损患者的肾脏结构和功能。在进行比较的同时，还将测量有或无蛋白尿增加的受试者在5年或更长时间内肾功能下降的速度，以确认肾功能可能会独立于蛋白尿而下降。肾脏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.