PREVENTION OF DIABETIC NEPHROPATHY IN IDDM

该提案要求支持一项临床研究， 是否降低早期胰岛素的超滤 依赖性糖尿病与血管紧张素II抑制 转化酶可以逆转微量白蛋白尿， 肾小球滤过率逐渐下降， 在其他胰岛素依赖型糖尿病的研究中也有记载。 我们 现有263例胰岛素依赖型糖尿病患者， 糖尿病视网膜病变自然史的纵向研究 由眼科部门。 近70%的 受试者没有通过常规临床试验可检测到的蛋白尿。 程序. 在这些没有蛋白尿的个体中， 微量白蛋白尿的特征是白蛋白 定时尿液收集的放射免疫测定和那些个体 白蛋白排泄率超过15微克/分钟， 随机分为两组。 一组是患有 早期微量白蛋白尿（15至80微克/分钟）和第二次 组将包含那些有微量白蛋白排泄的个体 每例患者的白蛋白摄入量在81至250微克之间 分钟 血压不超过140/85的人 或正在接受抗高血压治疗的患者。 两组中的每一组将被随机分配到一个治疗组 对照组和治疗组给予转换 酶抑制剂的水平为20毫克/天。 微量蛋白 每三个月测量一次排泄率， 肾小球滤过率，每6个月评估一次 视网膜改变将每年进行一次。 意见将 在启动后的三年内进行 治疗 结果变量为微量白蛋白排泄 率、GFR的变化和视网膜病变严重程度的变化。 这项研究应该提供一个直接的假设， 糖尿病早期肾小球过度充盈， 在糖尿病的产生中起重要的致病作用 肾病

This proposal requests support for a clinical study designed to see whether lowering the hyperfiltration that occurs in early insulin dependent diabetes mellitus and inhibition of angiotensin II converting enzyme will reverse microalbuminuria and prevent the progressive decline in glomerular filtration rate that has been documented in other studies of insulin dependent diabetes. We have available 263 cases of insulin dependent diabetes presently in a longitudinal study of the natural history of diabetic retinopathy by the Department of Ophthalmology. Nearly 70 percent of the subjects do not have proteinuria detectable by routine clinical procedures. In these individuals without proteinuria, the rate of microalbuminuria will be characterized by an albumin radioimmunoassay of timed urine collections and those individuals with albumin excretion rates in excess of 15 micrograms/min will be randomized into two groups. One group will be patients with early microalbuminuria (15 to 80 micrograms/min) and the second group will contain those individuals with microalbumin excretion rates ranging between 81 and 250 micrograms of albumin per minutes. No individual with a blood pressure greater than 140/85 or who is receiving antihypertensive therapy will be included. Each of the two groups will be randomized into a treatment group and a control group and the treatment group given converting enzyme inhibitors at a level of 20 mg/day. Microalbumin excretion rates will be measured every three months and glomerular filtration rates every six months and assessment of retinal changes will be made on an annual basis. Observations will be made over a period of three years following initiation of treatment. Outcome variables will be microalbumin excretion rate, change in GFR and change in the severity of retinopathy. This study should provide a direct test of the hypothesis that the hyperprofusion of the glomeruli in early diabetes mellitus play an important pathogenetic role in the production of diabetic nephropathy.