Australians Identify Protein That Could Mark Alport Syndrome’s Progression

Australian researchers have identified a protein that is a possible biomarker of the progression of Alport syndrome and similar kidney diseases.

They detected higher than normal levels of the protein mindin in the urine of mice with an Alport-like disease. Those levels reflect increased protein leakage from damaged kidneys, they said.

The team now plans to study the potential marker in humans with Alport and similar kidney diseases. The findings could lead to studies on whether preventing the molecular processes involved in the production of the protein can slow kidney disease progression.

Researchers’ study, which appeared in the journal Scientific Reports, was titled “Characterization of the early molecular changes in the glomeruli of Cd151−/− mice highlights induction of mindin and MMP-10.”

People with CD151 gene mutations develop a kidney disease similar to the one in Alport syndrome. In both conditions, the glomerular basement membrane, which is part of the kidney’s filtering system, becomes thicker and splits. Meanwhile, the cells lining the basement membrane, called podocytes, also become abnormal.

Eventually, the changes, accompanied by inflammation, lead to proteins leaking from the kidneys and kidney failure.

University of Newcastle researchers used mice that lacked a Cd151 gene to examine the molecular events seen in early stages of kidney disease. After discovering an array of kidney genes that were overactive, they honed in on two in particular: MMP-10 and the extracellular matrix protein mindin.

They discovered a link between higher MMP-10 activity and kidney disease. They also found mindin accumulating in the thickening portions of the glomerular basement membrane. This indicated that it could be a biomarker of kidney damage.

At the time they made these observations, the 3-week-old mice were displaying basement membrane abnormalities, but had yet to develop glomerular inflammation and scarring.

The researchers did not detect the protein in the kidneys of younger mice, which they checked just before or five days after birth. This indicated that it is involved in relatively early disease processes, but not in  initial disease events.

Researchers also detected mindin in the mice’s urine. In fact, mice with mindin also had substantial levels of other proteins in their urine. The team failed to detect mindin in the urine of mice with low protein leakage from the kidneys. This suggested that it could be an easily accessible biomarker of kidney disease progression.

The team said the next step is to explore whether mindin can be found in the urine of people with Alport syndrome and similar kidney diseases.