Progression of Chronic Renal Disease

Lance Dworkin MD
Principal investigator:
Lance Dworkin, MD

Most forms of chronic renal disease are progressive, eventually leading to end-stage renal failure. While progression may result from ongoing activity of the disease process that initially damaged the kidney, in many cases it occurs as a result of secondary adaptations to injury that are common to most forms of kidney damage. In fact, in the short term, these adaptations may appear beneficial and tend to return total kidney function toward normal; however, in the long term, they are maladaptive and promote progressive nephron destruction.

Initial studies in our laboratory focused on the hemodynamic adaptations to injury, and demonstrated that many forms of chronic renal injury were associated with an increase in hydraulic pressure within the glomerular capillaries. We showed that maneuvers that reduced glomerular pressure, including low salt and protein diets and antihypertensive therapy, could prevent renal injury.

Subsequently, we reported that compensatory renal growth in damaged kidneys was also associated with progressive kidney failure. Current studies are examining the role of cytokines, growth factors and their receptors in modulating compensatory kidney growth and injury.

Some of our most recent work has used physiologic, cell biologic and molecular techniques to examine the role of hepatocyte growth factor and its receptor, c-met, in the injury and repair process in kidney cells in culture and in a variety of animal models of acute and chronic renal disease. We are also investigating the mechanisms by which antihypertensive agents, particularly those that block the renin-angiotensin system, reduce renal injury.