Monitoring transplant kidney function with MRI

描述（由申请人提供）：慢性肾脏疾病（CKD）正在悄悄地成为影响美国医疗保健系统的一个重大问题，有2000万美国人处于CKD风险或患有CKD。这对社会来说是一个沉重的负担，因为预计到2010年，仅用于这些人的医疗保健预算就将超过250亿美元。人类付出的代价甚至更大，因为这些患者患心血管疾病的风险明显更高，寿命缩短。肾移植可以替代衰竭的肾功能，并抵消其中一些并发症。然而，在许多情况下，移植只是一种临时措施，因为同种异体移植通常不会持续一生。目前，血清肌酐（Scr），估计肾小球滤过率（eGFR）和蛋白尿用于监测移植受者的肾功能。这些措施是有帮助的，但在移植环境中很容易失去真正的功能，同时保持稳定的Scr。因此，评估个体进行性肾功能障碍和评估肾功能障碍新标志物的其他方法至关重要。我们假设肾脏灌注和氧合的变化伴随或甚至先于当前方法测量的功能的显著变化。MRI能够非侵入性地评估区域灌注和氧合，以允许氧输送和利用的区域相关性。结合这些措施与肾功能的临床标志物，可以为我们提供一个强大的方法，在体内监测同种异体移植物的功能和肾保护治疗的反应。该项目的具体目的是：1）验证用于测量肾灌注和氧生物利用度的当前MR技术; 2）确定MR测量的局部肾内灌注和氧生物利用度是否与慢性同种异体移植物功能障碍的发作和进展相关; 3）确定氯沙坦长期血管紧张素受体阻断是否改变活体供体同种异体移植物中MR测量的肾内灌注和氧生物利用度。

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) is quietly becoming a significant problem affecting the United States healthcare system, with 20 million Americans either at risk for or suffering from CKD. This is a significant burden on society, as the Medicare budget alone for these individuals is expected to exceed $25 billion by 2010. The cost to humanity is even greater, as these patients have a significantly higher risk of cardiovascular disease and a shortened lifespan. Kidney transplantation can replace failed kidney function and offset some of these complications. However, in many instances transplantation is only a temporary measure, as allografts usually do not last a lifetime. Currently serum creatinine (Scr), estimated glomerular filtration rate (eGFR) and proteinuria are used to monitor kidney function in transplant recipients. Such measures are helpful, but it is readily possible in the transplant setting to lose true function while maintaining stable Scr. Hence, additional means of assessing progressive kidney dysfunction in the individual and for evaluating novel markers of kidney dysfunction are of utmost importance. We hypothesize that changes in kidney perfusion and oxygenation accompany or even precede marked changes in function as measured by current methods. MRI is able to non-invasively assess regional perfusion and oxygenation to allow for regional correlations of oxygen delivery and utilization. Combining these measures with the clinical markers of kidney function can provide us with a robust methodology for in vivo monitoring of allograft function and its response to renoprotective therapies. The Specific Aims of the project are to 1) validate current MR techniques for measuring renal perfusion and oxygen bioavailability; 2) determine whether MR measured regional intrarenal perfusion and oxygen bioavailability correlate with the onset and evolution of chronic allograft dysfunction; and 3) determine whether long-term angiotensin receptor blockade by losartan alters MR measured intrarenal perfusion and oxygen bioavailability in living donor allografts.