Monitoring transplant kidney function with MRI

描述(申请人提供)：慢性肾脏疾病(CKD)正悄然成为影响美国医疗体系的一个重大问题，有2000万美国人面临CKD的风险或遭受CKD的折磨。这对社会来说是一个巨大的负担，因为到2010年，仅针对这些人的医疗保险预算就预计将超过250亿美元。人类的代价甚至更大，因为这些患者患心血管疾病的风险明显更高，寿命也更短。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。目前用于监测肾移植受者肾功能的指标有血肌酐(Scr)、估计肾小球滤过率(EGFR)和蛋白尿。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的新标记物的其他手段是至关重要的。我们假设肾脏灌注和氧合的改变伴随着或甚至先于目前方法所测量的显著的功能改变。磁共振成像能够非侵入性地评估区域的血流和氧合，以允许区域的氧气输送和利用的相关性。将这些指标与肾功能的临床标志物相结合，可以为体内监测移植肾功能及其对肾保护治疗的反应提供可靠的方法学。该项目的具体目标是：1)验证目前用于测量肾脏血流灌注和氧气生物利用度的MR技术；2)确定MR测量的区域肾内灌注量和氧气生物利用度是否与慢性同种异体移植功能障碍的发生和演变相关；以及3)确定氯沙坦长期阻断血管紧张素受体是否改变了MR测量的活体供肾肾内灌注量和氧气生物利用度。

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.