Richard A. Zager
M.D., Northwestern University, 1969.
The primary focus of the renal program is the study of how the kidney adapts to toxic and ischemic insults, resulting in acquired resistance to further attack. Research conducted over the last 2 years has indicated that sublethal injury evokes adaptational changes in the plasma membrane which render the membrane resistant to oxidative and phospholipase mediated damage. While several echanisms can contribute to this state, the dominant one identified as of this time is an upregulation of membrane cholesterol content. This leads to a decrease in membrane fluidity, which, by itself is cytoprotective. In addition, there is a injury-evoked perturbation of cholesterol cycling within the cell, culminating in the excess production of cholesterol esters. Thelatter may then be directly cytoprotective by positively influencing mitochondrial energy production and decreasing oxygen free radical generation. The laboratory is now addressing how clinically relevant agents, administered routinely to bone marrow transplant patients, impact these pathways. One key factor is cyclosporine A which has pronounced effects on the above noted events. As one example, cyclosporine inhibits normal cholesterol homeostasis, thereby altering cellular responses to attack.
A second and unrelated focus of this laboratory is the study of vitamin D metabolism, its response to systemic cytokines, and how these factors evoke hypocalcemia in critically ill patients. These clinical studies are being undertaken in both BMT and non BMT patients, the latter hospitalized in ICUs in UW hospitals. This group has demonstrated that hypocalcemia occurs in as many as 90% ICU patients, and is equal to APACHE II scores in predicting adverse patient outcomes. These studies also have a basic research component as key hypotheses derived from the clinical data are tested in a laboratory setting.
Post-ischemic azotemia as a partial 'brake', slowing progressive kidney disease.. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 28(6):1455-62.. 2013.
Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease.. Kidney international. 83(6):1029-41.. 2013.
HMG-CoA Reductase Activation and Urinary Pellet Cholesterol Elevations in Acute Kidney Injury.. Clinical journal of the American Society of Nephrology : CJASN. 6(9):2108-13.. 2011.
Renal cortical albumin gene induction and urinary albumin excretion in response to acute kidney injury.. American journal of physiology. Renal physiology. 300(3):F628-38.. 2011.
MCP-1 gene activation marks acute kidney injury.. Journal of the American Society of Nephrology : JASN. 22(1):165-75.. 2011.
Acute Unilateral Ischemic Renal Injury Induces Progressive Renal Inflammation, Lipid Accumulation, Histone Modification, And 'End Stage' Kidney Disease.. American journal of physiology. Renal physiology. 301(6):F1334-45.. 2011.
Chimeric maternal cells in offspring do not respond to renal injury, inflammatory or repair signals.. Chimerism (Print). 2(2):42-49.. 2011.
Progressive histone alterations and proinflammatory gene activation: consequences of heme protein/iron-mediated proximal tubule injury.. American journal of physiology. Renal physiology. 298(3):F827-37.. 2010.
Acquired cytoresistance in the setting of hematopoietic cell transplantation.. Clinical journal of the American Society of Nephrology : CJASN. 5(12):2150-3.. 2010.
Parenteral iron formulations differentially affect MCP-1, HO-1, and NGAL gene expression and renal responses to injury.. American journal of physiology. Renal physiology. 299(2):F426-35.. 2010.
Uremia impacts renal inflammatory cytokine gene expression in the setting of experimental acute kidney injury.. American journal of physiology. Renal physiology. 297(4):F961-70.. 2009.
Renal ischemia-reperfusion injury upregulates histone-modifying enzyme systems and alters histone expression at proinflammatory/profibrotic genes.. American journal of physiology. Renal physiology. 296(5):F1032-41.. 2009.
Renal ischemia-induced cholesterol loading: transcription factor recruitment and chromatin remodeling along the HMG CoA reductase gene.. The American journal of pathology. 174(1):54-62.. 2009.
Uremia induces proximal tubular cytoresistance and heme oxygenase-1 expression in the absence of acute kidney injury.. American journal of physiology. Renal physiology. 296(2):F362-8.. 2009.
BRG1 increases transcription of proinflammatory genes in renal ischemia.. Journal of the American Society of Nephrology : JASN. 20(8):1787-96.. 2009.
Endotoxin mediates recruitment of RNA polymerase II to target genes in acute renal failure.. Journal of the American Society of Nephrology : JASN. 19(7):1321-30.. 2008.
Maleate nephrotoxicity: mechanisms of injury and correlates with ischemic/hypoxic tubular cell death.. American journal of physiology. Renal physiology. 294(1):F187-97.. 2008.
Toll-like receptor (TLR4) shedding and depletion: acute proximal tubular cell responses to hypoxic and toxic injury.. American journal of physiology. Renal physiology. 292(1):F304-12.. 2007.