Penn State Hershey Nephrology Research
The Division of Nephrology is actively engaged in research programs which are intended to find ways to prevent or cure both acute and chronic kidney diseases. Some of the research projects currently in progress include:
The role of inflammation in acute kidney injury (Reeves, Gao). Acute kidney injury occurs in about 5% of patients admitted to hospitals. Many of these individuals die or suffer permanent kidney damage. Investigators here have made the discovery that certain molecules (cytokines) produced by the immune system play an important role in causing acute renal failure. They have also discovered that certain immune cells within the kidney may reduce inflammation and kidney injury. Efforts are underway to learn how these cells, and the molecules they produce, affect kidney cells in response to toxic medications or ischemia.
Inflammation and diabetic nephropathy (Reeves, Awad). Diabetes is now the most common cause of renal failure in the United States. Drs. Reeves and Awad, are examining how a small protein, tumor necrosis factor (TNF), may promote diabetic kidney damage. Tumor necrosis factor is produced by the immune system and by the kidney. Preliminary observations indicate that the production of tumor necrosis factor is increased in diabetes. Dr. Awad has also found that ablation of macrophages, which are potent producers of TNF, reduces the development of diabetic nephropathy. They are studying the production of TNF in both humans with diabetes and in animal models of diabetes.
The role of ion channels in acute kidney injury (Reeves, Gao). Ion channels are small pores in the membrane of cells which regulate the movement of ions, such as sodium, potassium, and chloride, in and out of cells. If the movement of ions is not precisely regulated, injury or death of the cells may occur. Dr. Reeves and his team have discovered that deletion or inhibition of a certain ion channel, TRPM2, which allows movement of calcium, potassium and sodium, reduces ischemic kidney injury. They are now examining the factors which cause the activation of these channels, and how the movement of these ions leads to injury.
Early diagnosis of acute kidney injury. Acute kidney injury has a high mortality. A number of biomarkers have been proposed to allow for earlier diagnosis and perhaps better treatment of AKI. In conjunction with Dr. Judy Howyrlak in the Division of Pulmonary and Critical Care Medicine, Dr. Reeves is exploring the utility of some of these novel biomarkers to diagnose or prognosticate patients with AKI in the ICU. In conjunction with Dr. Jong-in Hahm (Georgetown University) he is also testing a novel nanomaterial platform for more sensitive detection of biomarkers. Dr. Reeves and Dr. Tadigadapi (University Park) are working to develop a real-time measure of kidney function which can be used to monitor kidney function in critically ill patients. Finally, he is collaborating with Dr. Jay Raman (Urology) to determine the ability of biomarkers to detect kidney injury during kidney surgery and lithotripsy.
Natural history of acute kidney injury (Reeves, Ghahramani). Drs. Reeves and Ghahramani are collaborating with Dr. Vern Chinchilli (Department of Public Health Sciences) in an NIH sponsored multicenter study of the natural history of acute kidney injury (ASSESS-AKI). This 5 year study will examine the long term health outcomes of 600 patients with AKI compared with a matched control population.
Peer-led mentoring program for patients with chronic kidney disease and their caregivers (Ghahramani). Patients with CKD and their family members face many challenges in dealing with the disease and the decisions that relate to choice of treatment. Receiving supportive mentoring from well-adjusted individuals who share similar experiences has had a positive influence on adjustment with some chronic diseases. In a study supported by Patient Centered Outcomes Research Institute (PCORI), Dr. Ghahramani is conducting a study to evaluate the effect of peer mentoring on patient engagement and quality of life, as well as caregiver burden.
Geographic disparities in kidney disease management (Ghahramani). Little is known concerning the impact of geography on the incidence and/or treatment of kidney disease. Using survey methods, meta-analysis and database analysis, Dr. Ghahramani performs observational studies in the following general areas: Geographic aspects of renal disease; Rural/urban disparities in kidney transplantation; The impact of perceptions of physicians and patients on quality of healthcare.
The treatment of anemia in kidney disease (Verma). Anemia is a common complication of kidney disease. In addition to causing generalized fatigue among patients, anemia may accelerate heart disease and require blood transfusions, which carries a small risk of transmitting certain diseases. For the past two decades, dialysis patients have benefited from treatment with erythropoietin to correct their anemia. Researchers in the Division of Nephrology are involved in studies to test new derivatives of erythropoietin in conjunction with iron in order to develop optimal treatment regimens for patients with anemia.
Tissue plasminogen activator in renal fibrosis (Hu). Kidney fibrosis is a common final pathway for various types of kidney disease. Dr. Hu has discovered that a plasma protease, tissue plasminogen activator (TPA), may play an important role in the progression of kidney fibrosis through receptor-mediated effects on interstitial fibroblasts and myofibroblasts. His current research is focused on elucidating the actions of TPA on fibroblast proliferation and turnover as well as the intracellular signaling pathways which regulate these processes.
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