Serum Biomarker of Fibrosis May Help Predict Diabetic Kidney Disease
NEW YORK (Reuters Health) – Elevated levels of a polyubiquitinated form of PTEN (phosphatase and tensin homolog) protein may be a marker of kidney-function decline and progression to kidney disease in people with type-2 diabetes, a new study suggests.
“Measurement of this form of modified PTEN in serum may have value in assessing a person’s risk for progressive kidney disease above and beyond standard clinical measurements, such as glomerular filtration rate, blood pressure and proteinuria,” said Dr. Helen Looker, staff scientist in the section for chronic kidney disease, National Institute of Diabetes and Digestive and Kidney Diseases, in Phoenix, Arizona.
“Diabetic kidney disease (DKD) is one of the leading causes of kidney failure worldwide and in the U.S. Early treatment is important to try and minimize loss of kidney function, but current measures may often be normal in the early stages of DKD. As a result, there is a lot of interest in identifying new biomarkers which are associated with risk of progression of DKD,” Dr. Looker told Reuters Health by email.
Fibrosis is a key driver of chronic kidney disease. The polyubiquitinated form of PTEN is associated with kidney disease in animal studies and is a marker of a pro-fibrotic mechanism, which theoretically could be at play in DKD, Dr. Looker said.
“We were interested to see if this modified form of PTEN might be predictive of DKD progression and we are well placed to address that issue as we have a decades-long partnership with local American Indians who have taken part in a series of kidney function studies run by the NIDDK over the past 40 years,” she explained.
Using stored serum from these studies, the researchers measured this modified form of PTEN in 154 women and 80 men with or at high risk for DKD.
During a median follow-up of 6.3 years, higher serum levels of modified PTEN were associated with a nearly four-fold greater risk of at least a 40% loss of glomerular filtration rate (HR, 3.95 for the fourth versus first quartile; P<0001), the researchers report in the American Journal of Kidney Diseases.
Higher levels of modified PTEN were also associated with a more than a five-fold increased risk of the onset of kidney failure over a median follow-up of 15.8 years (HR, 5.66 for quartile four versus one; P=0.001).
“We were also able to show in a smaller sub-group of participants who had earlier undergone research kidney biopsies that serum measures of this modified form of PTEN were also associated with structural lesions that are among the earliest signs of DKD,” Dr. Looker told Reuters Health.
“This is new data and further work needs to be done before it can be included in clinical practice,” she cautioned. “Further study of the role of this form of PTEN in human disease is important and hopefully we will see other studies looking to replicate our findings in other populations.”
SOURCE: https://bit.ly/39syZPV American Journal of Kidney Diseases, online September 22, 2021.
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