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New therapeutic targets in diabetic kidney disease. A role of GDF-15?


Title:  New therapeutic targets in diabetic kidney disease. A role of GDF-15?
Investigator:  A Bidadkosh
Promotor: RH Henning
Co-promoter(es):  LE Deelman, JH Buikema
Summary:  Type 2 diabetes is quickly becoming a disease of epidemic proportions and despite glycaemic control, diabetic nephropathy remains a common and serious complication of diabetes. Intervention in earlier stages of diabetic renal disease, when overt nephropathy is not yet present, appears to be superior as compared to late intervention. Thus, new strategies aiming at early detection and treatment of kidney disease, before functional and/or structural damage is present, may hold promise to further delay the progression of diabetic nephropathy on top of current established therapies.

Studies in early experimental diabetes identified growth differentiation factor 15 (GDF15) as a factor that is upregulated immediately after induction of diabetes. Further, mice that were genetically deleted for GDF15 demonstrated enhanced tubular damage in diabetes, indicating that GDF15 is a protective factor for the kidney. In a translational approach we have further demonstrated that GDF15 predicts for the progression of type 2 diabetes in patients, demonstrating that GDF15 may become an important biomarker for disease progression. Taken together, our studies demonstrate that GDF15 may become an important new tool for detection and treatment of diabetic kidney disease.

Our current line of research focuses on the identification of drugs that modulate GDF15 levels in both patients and animals. New advanced genetic models are being developed to further investigate the role of GDF15 in diabetes. Finally, the involvement of GDF15 in disease progression is extended to obesity induced diabetes, hypertension and hyperlipidemia collectively known as metabolic syndrome.

Financing:  Tasman bursary
Start:  1-03-2014
End:  1-03-2016

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