Nephrology Research
- Progression of Chronic Renal Disease
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.
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