Stress-activated protein kinases - a common pathway of progressive kidney disease.

Funded Activity Summary

Patients who progress to end-stage renal failure require treatment by life-long dialysis or kidney transplantation. In addition, renal failure is a strong and independent risk factor for heart attack. Renal failure is a major health problem in our community in terms of patient welfare and the substantial financial cost of renal replacement therapy and cardiac complications. Even with recent improvements in the control of blood pressure, we still have far to go in terms of halting progression and disease remission. Current therapies are still based on non-specific anti-inflammatory drugs which have substantial, dose-limiting side effects. Indeed, our current therapies do not even target the some of the critical pathogenic processes of progressive kidney disease, such as apoptotic cell death and fibrosis. Therefore, it is important to identify common mechanisms of progressive kidney disease. Irrespective of the nature of the initial renal insult, progressive forms of kidney disease show common pathogenic processes of inflammation, apoptotic cell death and fibrosis that inexorably lead to end stage renal failure. Recent studies from our laboratory, and others, suggest that these three pathogenic processes operate via a common pathway called the SAPK (stress-activated protein kinases). This hypothesis will be tested by blocking the SAPK pathway in three different animal models of kidney disease which feature these key pathogenic processes (inflammation, apoptosis cell death and fibrosis). Blockade of the SAPK pathway will be achieved by means of pharmaceutical drugs and using gene deficient mice. If this hypothesis were proven, this would provide a well-defined therapeutic target for the treatment of progressive kidney disease. Indeed, since inhibitors of the SAPK pathway are already in clinical trials for other indications, targeting this mechanism in progressive kidney disease is a realistic goal.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $581,750.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Nephrology And Urology

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Glomerular inflammation | Glomerulonephritis | Immunopathology | Kidney | Kidney diseases | MAP kinases | Pathogenic mechanisms | Renal interstitial fibrosis

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