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. ? ?
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