DIABETIC NEPHROPATHY

糖尿病肾病

• 批准号: 6448967
• 负责人: MICHAEL MAUER
• 金额: $ 18.5万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6448967
• 关键词: FK506; artificial immunosuppression; biopsy; clinical research; cyclosporines; diabetic nephropathy; extracellular matrix; human subject; human therapy evaluation; immunoelectron microscopy; immunofluorescence technique; in situ hybridization; insulin dependent diabetes mellitus; kidney transplantation; longitudinal human study; messenger RNA; pancreas transplantation; renal glomerulus; renal toxin; ultrasonography

These continuation studies focus on a large pancreas transplant (PT) population of insulin dependent diabetic (IDDM) patients (pts) in order to better understand diabetic nephropathy (DN), the leading cause of renal failure. Objectives are: (a) to determine whether PT can arrest or reverse the early or the more established lesions of DN, (b) describe the nature of and the message (MRNA) for the extracellular matrix (ECM) molecules which accumulate to produce DN, (c) to evaluate renal structural risk factors for DN, and (d) to describe the structural and functional nephrotoxicity of immunosuppression drugs [Cyclosporin (CSA) and Tacrolimus (FK506)] used in PT. Pts include those with long IDDM duration and established DN lesions undergoing PT alone (PTA), and for the study of early DN lesions, IDDM pts with PT performed a few years after kidney transplant (PAK). We will evaluate the effects of PT on the early and late DN lesions by comparing baseline with 5, 10, and 15 year postPT renal biopsies (bx). Controls will include IDDM pts not undergoing PT with bx at parallel times of native or transplanted kidneys. We will also determine from these controls if DN lesions develop at linear rates and where different lesions develop at different rates. We will study whether glomerular number (GN) is a risk factor for DN in native kidneys by estimating GN from prePT renal bx and ultrasound studies. ECM dynamics will be studied by immunofluorescence microscopy and quantitative immunogold EM immunochemistry and by in situ hybridization. We will evaluate the relationship of dose, blood levels, and duration of CSA and FK506 therapy to nephrotoxicity by morphometric measure of interstitial and glomerular scarring in PTA recipients.

这些继续研究着重于大型胰腺移植（PT） 胰岛素依赖性糖尿病（IDDM）患者（PTS）的种群 更好地了解糖尿病性肾病（DN），肾脏的主要原因 失败。目标是：（a）确定PT是否可以逮捕或反向 DN的早期或更既定的病变，（b）描述性质 细胞外基质（ECM）分子的信息（mRNA） 积累以产生DN，（c）评估肾脏结构风险 DN的因素，以及（D）描述结构和功能的因素 免疫抑制药物的肾毒性[环孢菌素（CSA）和 pt中使用他克莫司（FK506）。 PT包括持续时间长的pt 并建立了单独接受PT（PTA）的DN病变，并研究 早期DN病变，肾脏几年后，IDDM PT进行了几年 移植（PAK）。我们将评估PT对早期和晚期的影响 DN病变通过将基线与5年，10年和15年肾脏进行比较 活检（BX）。控件将包括IDDM pts不接受BX的PT 天然或移植肾脏的平行时间。我们还将确定 如果DN病变以线性速率和位置发育 不同的病变以不同的速度发展。我们将研究是否 肾小球数（GN）是本地肾脏DN的危险因素 从Prept肾脏BX和超声研究中估算GN。 ECM动力学 将通过免疫荧光显微镜和定量研究 免疫金EM免疫化学和原位杂交。我们将 评估剂量，血液水平和CSA和持续时间的关系 FK506通过间隙的形态计量测量对肾毒性进行治疗 和PTA受体中的肾小球疤痕。