1) Kidney transplantation and 2) Diabetic kidney disease.

• Kidney Transplantation
  
  Renal transplantation is the number one treatment for end-stage renal disease; however, the demand for kidney transplantation far exceeds the supply of donor kidneys. In 2001, Ohio performed the 6th highest number of kidney transplants in the United States (about 4,000). In 2000, there were a total of 13,332 kidney transplants performed while as of early 2002, about 51,000 patients in this country are on the waiting list. Chronic rejection still remains one of the difficult problems in renal transplantation. It is known that both immune and non-immune factors influence chronic rejection. Warm ischemia/reperfusion (I/R) injury has been identified in experimental studies as a non-immune factor that contributes to long-term graft dysfunction. I have focused on endothelin, a potent renal vasoconstrictor released from the endothelial cell as a possible mediator of I/R injury. It appears the endothelin levels are increased in these injured kidneys. I am also studying the contribution of factors such as complement, cytokines, and/or adhesion molecules to I/R injury in the kidney. Specifically, many of the events involved in the I/R injury occur in the smallest vessels within the kidney. Thus, I use two techniques to study renal function. I determine whole kidney function with clearance techniques and also study the renal microcirculation following I/R injury. The microcirculation studies using videomicroscopy provide a means to observe the renal microcirculation in vivo so that immediate changes following I/R injury can be studied. The long rang goal of this work is to provide a basis for pharmacological treatment of these injured kidneys to abolish the ischemic damage and expand the donor pool.
   
• Diabetic Kidney Disease
  
  Type 1 diabetes is the number one cause of end stage renal disease with renal transplantation serving as the final means of treatment. Agents like angiotensin converting enzyme inhibitors can slow the progression of diabetic nephropathy. I recently showed that one of the cholesterol lowering agents, lovastatin, could also slow the progression, presumably through mechanisms independent of its lipid lowering effect. My laboratory is studying the hypothesis that lovastatin has direct renal vasodilatory effects on the renal microcirculation to help maintain renal function. This effect may be mediated through its action on the release of vasoconstrictors/vasodilators from the renal microvascular endothelium, which modulate vascular tone. In a rodent model of diabetes, I measure renal function and study the renal microcirculation by direct visualization with videomicroscopy. The long-range goal is to understand mechanisms involved in diabetic nephropathy and to provide better treatment.