Christopher Lu, M.D.
Professor of Internal Medicine
Medical Director, Renal Transplantation

Ischemic acute kidney injury (AKI - previously called "acute renal failure" or "acute tubular necrosis") confronts the physician with major clinical problems, and the scientist with fundamental unsolved questions. The physician is confronted a disease with no accepted treatment other than supportive care. Although there is often some renal recovery, the acute mortality and morbidity remains high, and the longterm problems include progressive chronic kidney disease and longterm mortality. The scientist is confronted by a disease where the underlying pathophysiology is not understood. Although it is now recognized that the initial insult to the kidney is exacerbated by a maladaptive inflammatory response, how injury is translated into inflammation remains a fundament unsolved problem.

The overall goal of our laboratory is elucidating this unsolved problem in the hope this will led to more effective therapies. To this end, we use in vivo models of ischemic AKI in mice, and in vitro model systems to perform detailed studies of proinflammatory genes activated by renal ischemia/ reperfusion. We have found that molecules, normally residing within healthy cells, are released into the extracellular space when renal cells are injured by ischemia in vivo and in vitro. These molecules elicit activate proinflammatory genes (see recent references). We are also translating this bench research into the clinic by studying clinically indicated pre-transplant renal biopsies; these biopsy studies will determine if the genes associated with the inflammatory response to ischemia in mice also are activated in man. In addition to addressing fundamental questions, these clinical studies may predict the course and guide therapy of renal transplant recipients.

Ischemic AKI inevitably occurs during the process of renal transplantation - the donor hypotension, cold storage, and the transplant surgery. The inflammatory response to this allograft ischemia will include recipient leukocytes that should exacerbate allograft rejection Thus, our studies will also help us understand allograft rejection.

Research Interests:

transplant rejection
acute kidney injury (acute renal failure)
perinatal infections

Recent Publications:

Kielar ML, John R, Bennett M, Richardson JA, Shelton JM, Chen L, Jeyarajah DR, Zhou XJ, Zhou H, Chiquett B, Nagami GT, Lu CY. "The maladaptive role of interleukin 6 in ischemic acute renal failure." J Am Soc Nephrol 16(11):3315-25, 2005

Zhang Y, Woodward VK, Shelton JM, Richardson JA, Zhou XJ, Link D, Kielar ML, Jeyarajah DR, Lu CY. "Ischemia/reperfusion induces G-CSF gene expression by renal medullary thick ascending limb cells in vivo and in vitro." Am J Physiol Renal Physiol 286:F1193-201, 2004

Wang Y, John R, Chen J, Richardson JA, Shelton JM, Bennett M, Zhou XJ, Nagami GT, Zhang Y, Wu QQ, Lu CY. "IRF-1 promotes inflammation early after ischemic acute kidney injury." J Am Soc Nephrol 20:1544-55, July 2009

Wu Q, Wang Y, Senitko M, Meyer C, Wigley WC, Ferguson DA, Grossman E, Chen J, Zhou XJ, Hartono J, Winterberg P, Chen B, Agarwal A, Lu CY. "Bardoxolone Methyl (BARD) ameliorates ischemic AKI and increases expression of protective genes - Nrf2, PPAR gamma, and HO-1." Am J Physiol Renal Physiol, in press 2011

Chen J, John R, Richardson J, Shelton JM, Zhou X, Wang Y, Wu Q, Hartono J, Winterberg P, Lu CY. "Toll-like receptor 4 regulates early endothelial activation during ischemic acute kidney injury." Kidney Int 79:288-299, 2011

Significant Publications:

Lu CY, Calamai EG, Unanue ER. "A defect in the antigen-presenting function of macrophages from neonatal mice." Nature 282:327-329, 1979

Redline RW, Lu CY. "Role of local immunosuppression in murine fetoplacental listeriosis." J Clin Invest 79:1234-1241, 1987

Penfield JG, Wang Y, Li S, Kielar MA, Sicher SC, Jeyarajah DR, Lu CY. "Transplant surgery injury recruits recipient MHC class II-positive leukocytes into the kidney." Kidney Int 56:1759-1769, 1999

Lu CY, Penfield JG, Kielar ML, Vazquez MA, Jeyarajah DR. "Perspectives in basic science: Hypothesis: is renal allograft rejection initiated by the response to injury sustained during the transplant process?" Kidney Int 55:2157-2168, 1999

Lu CY, Hartono J, Senitko M, Chen J. "The inflammatory response to ischemic acute kidney injury: a result of the 'right stuff' in the 'wrong place'?" Curr Opin Nephrol Hypertens 16(2):83-9, 2007