Researchers at the University of California, San Diego School of Medicine, the National Institutes of Health (NIH) and the Mayo Clinic have published promising results of a clinical study using an experimental anti-fibrotic and anti-inflammatory drug called pirfenidone to treat patients with diabetic nephropathy.
Diabetic nephropathy remains the leading cause of end-stage kidney disease (ESKD) in the United States. It is a common complication of diabetes, in which kidney cells are damaged as a result of high blood sugar levels.
The dramatic finding of this exploratory study is that an appropriate dose of pirfenidone not only halted decline but actually improved kidney function in these patients.
The principal damaging process is called fibrosis, or scarring, damages tiny blood vessels in the glomerulus, structures that filter and remove waste from the blood, and in between tubular cells.
Transforming growth factor beta (TGF-β) is a protein that controls many cellular functions, including extracellular matrix accumulation. TGF-β is stimulated in the diabetic kidney due to uncontrolled blood sugar and elevated blood pressure and can promote renal fibrosis.
Image of Diabetic Nephropathy
To date, therapies for diabetic nephropathy have been limited to drugs that improve blood pressure or control blood sugar levels, instead, pirfenidone seems to work by blocking TGF-β; in effect, shutting down the growth factors that cause renal fibrosis.
The UCSD researchers previously observed a very dramatic benefit in a mouse model of diabetic kidney disease, in a study published in JASN two years ago. The animal studies showed improvement in matrix accumulation at gene and protein levels with just four weeks of treatment.
Larger trials are required to pass the benefits to the patients.