Study: Molecules in urine predict diabetic kidney failure 5 to 10 years earlier


Study: Molecules in urine predict diabetic kidney failure 5 to 10 years earlier

A team from the University of Texas published a breakthrough study Thursday of a new test they say can accurately predict kidney failure five to 10 years beforehand, allowing more time for preventative treatment and avoid the need for kidney dialysis. Image courtesy of the Centers for Disease Control and Prevention

Small metabolic molecules naturally produced in the kidney are a more accurate predictor of future kidney failure in patients with diabetes than the conventional warning sign — protein in the urine — and could lead to earlier diagnosis and treatment, according to new research.

The global study by researchers at the University of Texas Health Science Center at San Antonio and published in the Journal of Clinical Investigation on Thursday found that levels of adenine, a metabolite produced in the kidney, in urine were both a predictive and a causative biomarker of looming progressive kidney failure in patients with diabetes.

The study used a kidney biopsy technique developed by UT Health San Antonio that enabled researchers to determine the locations of adenine and other small molecules in kidney tissues that make cells go in a healthy direction or in a disease pattern.

They found adenine was present around scarred blood vessels in the kidney and around tubular-shaped kidney cells that were being destroyed and that high levels were associated with all-cause mortality in study participants indicating the metabolite also was affecting other parts of the body.

The study looked at 1,200 patients across three ethnic cohorts including African-Americans, Hispanics and Caucasians in the United States with a separate study of the American Indian population. The researchers also evaluated a cohort of mostly Chinese, Asian Indians and Malay populations in a study based out of Singapore.

The finding that high urine adenine was associated with higher risk of kidney failure was consistent across the study populations.

The results are important, the research team says, because the standard approach of testing for protein, or albumin, in the urine is ineffective in up to half of all diabetic patients who go on to develop kidney failure because they do not have protein levels in their urine sufficient to suggest their true risk profile.

With 9 out of 10 diabetics — more than 37 million in the United States alone — at higher risk of kidney failure even though their urine contains little albumin, the study paves the way for screening to find out if patients are at a point five to 10 years before their kidneys give out, according to senior study author Dr. Kumar Sharma.

“Many patients with diabetes know they’re at risk of kidney disease, but if they don’t have protein in their urine, they think they are protected, Sharma, a professor and chief of nephrology at UT Health San Antonio and founding director of the Center for Precision Medicine, said in a news release.

“They could be feeling a false sense of security that there is no kidney disease occurring in their body,” Sharma said. “But in fact, in many cases, it is progressing and they often don’t find out until the kidney disease is pretty far advanced. And at that time, it is much harder to protect the kidneys and prevent dialysis.”

The research team was able to identify and isolate a small molecule that may block the major pathway of adenine production with medication they formulated reducing kidney adenine levels in mice with type 2 diabetes.

“The drug protected against all the major aspects of diabetic kidney disease without affecting blood sugar,” Sharma said. “The study is remarkable as it could pave the way to precision medicine for diabetic kidney disease at an early stage of the disease.”

Once a patient deteriorates to the point they need dialysis, he or she must have a fistula or catheter fitted and go on a dialysis machine for four hours, three times a week, to clean their blood.

Four in 10 diabetics with kidney failure die within five years, according to Sharma, who said a new therapy was badly needed.

“What we’re hoping is that by identifying patients early in their course and with new therapies targeting adenine and kidney scarring, we can block kidney disease or extend the life of the kidney much longer,” he said.

The study was funded by the National Institutes of Health and National Institute of Diabetes and Digestive and Kidney Diseases.


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