Gout Kidney Disease

Research on Uromodulin Associated Kidney Disease (UMAK)

Wake Forest Baptist Medical Center physician and researcher, Anthony Bleyer, MD, MS, a professor in the Section on Nephrology, together with a research team is working to identify individuals and families with potential genetic mutations that lead to Uromodulin Associated Kidney Disease (UMAK).  UMAK is a disease caused by a mutation (mistake) in one of the genes that makes the protein uromodulin.  Each individual has two genes that make most proteins.  In UMAK, one of the genes makes uromodulin normally, and the other makes uromodulin abnormally.

Uromodulin is a common protein that is produced in the kidneys.  This protein is excreted by the kidney into the urine.  It is the most common protein found in the normal human urine.  Uromodulin used to be called the Tamm Horsfall protein.  It has been studied for over thirty years, but still no one knows the function of normal uromodulin.

In UMAK, one of the uromodulin genes that inherited from the patients’ father or mother is mutated—or carries a mistake.  This mistake inhibits the secretion of uromodulin from the cell that normally produces it.  The abnormal uromodulin remains in the protein processing part of the cell called the endoplasmic reticulum.  The abnormal protein “gums up the works.”  It inhibits the normal uromodulin (produced by the healthy gene) from being secreted normally from the cell.  The uromodulin deposits in chunks that likely lead to cell death over time, leading to kidney failure.

Other members of the research team are: 

• Tom Hart, DDS., PhD, who oversees the basic research on UMAK that is performed at the National Institutes of Health;
• Vicki Robins, RN., research coordinator for the UMAK study at Wake Forest, who provides information on the studies being performed and helps to collect samples and data for the study.

UMAK Study Has Two Major Goals:

The UMAK study has two major goals:  to improve the understanding of UMAK and to find a treatment for this condition. 

The study’s current research activities include:

• Further characterizing uromodulin associated kidney disease by evaluating kidney function in affected individuals
• Evaluating the effects of allopurinol on progression of disease
• Basic laboratory research studying the mutation after it is introduced into cultured cells
• Developing a mouse that has a mutation in uromodulin