- Researchers have found a new biomarker in urine—other than albumin—that could aid with diagnosing kidney failure 5–10 years early.
- A drug that blocked the biomarker from being produced in mice protected against kidney damage.
- The researchers hope their findings will lead to new diagnostic tools and treatments for kidney failure.
The kidneys filter all the blood in the body for wastes, toxins, and excess fluids every 30 minutes.
Chronic kidney disease (CKD) happens when the kidneys are damaged and no longer filter blood as well as they used to. This means that waste and excess fluid can accumulate in the body, where they may contribute to conditions including heart disease and stroke.
Around 15% of adults in the U.S. have CKD, although most are undiagnosed. As CKD progresses, the kidneys increasingly lose function until they stop working, a stage known as kidney failure. To survive, patients with kidney failure require kidney transplants or dialysis—when an external machine cleans the blood.
Currently, albumin—a protein made by the liver—is considered an important diagnostic marker for kidney disease. However, up to 50% of patients with diabetes with a high risk of CKD and kidney failure have low levels of albumin in their urine.
New biomarkers for kidney failure could help clinicians diagnose and treat CKD before it progresses to later stages.
Recently, researchers investigated whether urine levels of adenine, a metabolite produced by the kidney, could predict kidney disease in people with diabetes. They found that higher adenine levels were linked to higher rates of kidney failure.
Dr. Donald A. Molony, distinguished teaching professor of the University of Texas System at McGovern Medical School University of Texas, who was not involved in the study, told Medical News Today:
“The most important implication of this study is that we now have a powerful biomarker that might allow us to identify individuals with early CKD at risk for disease progression.”
The study was published in The Journal of Clinical Investigation.
High levels of adenine in urine
For the study, the researchers analyzed urine sample data from over 1,200 patients with diabetes and impaired kidney function from three international research cohorts, including:
- African-American, Hispanic, and Caucasian individuals in the U.S.
- American Indian individuals
- an Asian cohort consisting mainly of Chinese, Asian Indians, and Malay populations
In each of the cohorts, the researchers found that higher levels of adenine were linked to higher rates of kidney failure. This also applied to patients with low levels of albumin in their urine.
Higher adenine levels were further linked to a higher risk of all-cause mortality. The researchers suggested that this means the metabolite may also affect other areas of the body.
In a further analysis, the researchers honed in on adenine levels of a subset of 40 patients with type 1 diabetes who had been given empagliflozin, an antidiabetic drug used to improve glucose control. After eight weeks of treatment, their adenine levels fell by 36.4%.
The researchers suggested that benefits from empagliflozin may be partly due to lower adenine levels. This idea is consistent with recent research, suggesting that empagliflozin reduces the risk of CKD progression.
The researchers further investigated whether modifying adenine levels affected kidney failure risk. To do so, they tested a drug that blocks a major pathway of adenine production in mouse models of type 2 diabetes.
Ultimately, the drug both reduced adenine levels in the mice and protected them against kidney injury and thickening of kidney walls—known as kidney hypertrophy—without affecting blood sugar.
Lastly, the researchers conducted biopsies of kidneys from human patients with and without diabetes using a new technique called spatial metabolomics. In doing so, they were able to determine the locations of adenine and other small molecules in kidney tissue.
Whereas low levels of adenine were present in healthy kidneys, they noted that adenine levels were elevated in certain areas of kidneys with diabetes, such as scarred blood vessels.
Dr. Molony saidthat the study has very few limitations and that the study design was robust with a ‘low risk of scientific bias.’
He added that while previous studies confirm the validity of adenine levels as a biomarker, they don’t necessarily present a causative link between adenine and CKD. He noted, however, that this study strongly suggests that high urinary adenine levels may, at least in part, cause kidney failure.
Meanwhile,Dr. Jared Braunstein, board certified internist with Medical Offices of Manhattan and contributor to LabFinder.com, who was not involved in the study, told MNT that the study is limited as most of its data comes from lab animals, as opposed to humans. He added that its small sample size also reduces the ‘power’ of the study.
MNT also spoke with Dr. Shuta Ishibe, professor of nephrology at Yale School of Medicine, who was also not involved in the study, about its limitations.
“Further investigation is required to determine whether endogenous adenine production contributes to the progression of [diabetic kidney disease] (DKD), or just serves as a biomarker, or potentially a combination of both,” he said.
A new drug to stop kidney failure?
“A significant portion of [the participants did] not have traditional clinical markers of CKD. These subjects had healthy kidney clearance function and no abnormal protein in the urine. Currently, these individuals would not be candidates for [adenine-lowering drugs due to their kidney function and absence of excess protein in their urine],” Dr. Molony said.
“Individuals can not ask for a rapid [adenine test at present]. It should be noted that the measure used in this study is not yet commercially available and has been used only in experimental conditions and not yet in routine clinical care.”
— Donald A. Molony
He said the study serves as evidence to introduce adenine-lowering drugs or other kidney protective interventions early on in treatment “that might otherwise not be considered until [excess protein occurs in the urine] or there is a rise in blood creatinine.”
“This study also opens up an entirely novel target for the development of therapeutics that might reduce progression to kidney failure,” he added.
How to reduce the risk of kidney failure
Dr. Molony noted that there are currently a number of evidence-based interventions that may significantly improve future kidney health and reduce progression to kidney failure by 50-70%.
He said these measures include:
- Healthy living such as exercise without heat stress, maintenance of an ideal body weight, avoiding excessive alcohol consumption, avoiding heat and dehydration, and quitting smoking.
- Achieving healthy blood pressure, generally systolic blood pressure of less than 125 in most patients and populations. People should discuss their personal ideal targets with their physician.
- Avoiding high and persistent daily doses of over-the-counter pain remedies.
- Restricting or reducing animal-source protein in the diet and avoiding protein loading.
He added that patients with an additional kidney disease risk, such as diabetes, should routinely visit their primary care physician to assess their kidney function.
If levels of albumin and other proteins are excessive in their urine, they may consider various drug regimens. He recommended patients consider ‘timely consultation’ with a kidney specialist.
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