Biomarker may lead to clinical laboratory testing that enables clinical pathologists and urologists to diagnose risk for diabetic kidney failure years before it occurs
Clinical laboratories working with nephrologists and urologists to diagnose patients experiencing urinary system difficulties know that albumin (excessive protein found in the urine) is a common biomarker used in clinical laboratory testing for kidney disease. But patients with diabetes generally have low protein in their urine due to that disease. Thus, it is difficult to diagnose early stage kidney failure in diabetic patients.
But now, researchers at the University of Texas Health Science Center at San Antonio (UT Health San Antonio) have discovered a biomarker called adenine (also found in the urine) which, they say, offers the ability to diagnose diabetic patients at risk of kidney failure significantly earlier than other biomarkers.
A UT Health San Antonio news release states, “Urine levels of adenine, a metabolite produced in the kidney, are predictive and a causative biomarker of looming progressive kidney failure in patients with diabetes, a finding that could lead to earlier diagnosis and intervention.”
The study’s senior author Kumar Sharma, MD, professor and Chief of Nephrology at UT Health San Antonio, said, “The finding paves the way for clinic testing to determine—five to 10 years before kidney failure—that a patient is at risk.”
“The study is remarkable as it could pave the way to precision medicine for diabetic kidney disease at an early stage of the disease,” said study lead Kumar Sharma, MD (above), professor and Chief of Nephrology at UT Health San Antonio, in a news release. This would be a boon to clinical laboratories and pathology groups that work with urologists to diagnose and treat diabetic patients who are at-risk for kidney failure. (Photo copyright: UT Health San Antonio.)
Completing the UT Health Study
Sharma and his team worked for five years to discover that the adenine molecule was damaging kidney tissue, News4SA reported. The research required the team to develop new methods for viewing small molecules known as metabolites.
“UT Health San Antonio is one of few centers in the US perfecting a technique called spatial metabolomics on kidney biopsies from human patients,” the news release notes. The kidney biopsies were obtained through the Kidney Precision Medicine Project (KPMP) and were gathered from various US academic centers.
“It’s a very difficult technique, and it took us several years to develop a method where we combine high resolution of the geography of the kidney with mass spectrometry analysis to look at the metabolites,” Sharma said.
Testing by the UT Health team unearthed “endogenous adenine around scarred blood vessels in the kidney and around tubular-shaped kidney cells that were being destroyed. Endogenous substances are those that naturally occur in the body,” the news release notes.
Findings Could Affect Diabetic Care
UT Health San Diego’s study findings could allow for early intervention and change the way diabetes care is managed, Sharma said.
“The study results are significant because until now, the most important marker for kidney disease has been protein (or albumin) in the urine. Up to half of diabetes patients who develop kidney failure never have much protein in their urine. As 90% of patients with diabetes (more than 37 million patients in the US) remain at increased risk despite low levels of albumin in their urine, this study has widespread consequences. It is the first study to identify these patients at an early stage by measuring this new causative marker in the urine,” the UT Health news release states.
“We’re hoping 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,” Sharma said.
Getting Ahead of Kidney Disease
Though many patients recognize their risk for kidney disease, those who do not have protein in their urine may not take the risk seriously enough, Sharma noted.
“They could be feeling a false sense of security that there is no kidney disease occurring in their body, 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,” he said in the new release.
“Once a patient needs dialysis, he or she must have a fistula or catheter placed and go on a dialysis machine three times a week, four hours at a time to clean the blood,” the news release states.
“The death rate is very high, especially in patients with diabetes,” Sharma added. “There is about 40% mortality within five years in patients with diabetes and kidney failure.”
Though measuring adenine in urine is a challenge, Sharma and his team developed a method that can be performed at UT Health San Antonio on at-risk patients with a doctor’s order. The test results go back to the patient’s doctor.
“The test is being approved for clinical use and right now it is an experimental test, but we expect it to be available for all patients in the near future.” Sharma told News4SA.
“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,” Sharma said in the news release.
And so, thanks to the UT Health researchers, pathologists and clinical laboratories may soon see a new diagnostic test biomarker that will help urologists identify diabetic patients at-risk for kidney failure years earlier than previously possible.
Some healthcare experts point to an “immunity gap” tied to the COVID-19 pandemic, while others suggest alternative theories such as temporary immunodeficiency brought on by COVID-19. In most cases, RSV causes “mild, cold-like symptoms,” but the CDC states it also can cause serious illness, especially for infants, young children, and older adults, leading to emergency room visits, hospitalizations, and an increased demand for clinical laboratory testing.
Pulmonology Advisor reported that the disease typically peaks between December and February, but hospitalizations this season hit their peak in November with numbers far higher than in previous years. In addition to infants and older adults, children between five and 17 years of age were “being hospitalized far in excess of their numbers in previous seasons,” the publication reported.
“Age by itself is a risk factor for more severe disease, meaning that the younger babies are usually the ones that are sick-sick,” pediatrician Asuncion Mejias, MD, PhD (above), a principal investigator with the Center for Vaccines and Immunity at Nationwide Children’s Hospital in Columbus, Ohio, told MarketWatch. Now, she added, “we are also seeing older kids, probably because they were not exposed to RSV the previous season.” Clinical laboratories in hospitals caught the brunt of those RSV inpatient admissions. (Photo copyright: Nationwide Children’s Hospital.)
Did COVID-19 Cause Immunity Gap and Surge in Respiratory Diseases?
CDC data shows that hospitalization rates linked to RSV have steadily declined since hitting their peak of 5.2 per 100,000 people in mid-November. In contrast, hospitalizations linked to the flu peaked in late November and early December at 8.7 per 100,000. Hospitalizations linked to COVID 19—which still exceed those of the other respiratory diseases—reached a plateau of 9.7 per 100,000 in early December, then saw an uptick later that month before declining in the early part of January, 2023, according to the CDC’s Respiratory Virus Hospitalization Surveillance Network (RESP-NET) dashboard.
Surveillance by the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD) revealed a similar pattern: An early peak in weekly numbers for emergency room visits for RSV, followed by a spike for influenza and steadier numbers for COVID-19.
So, why was the RSV outbreak so severe?
Respiratory diseases tend to hit hardest in winter months when people are more likely to gather indoors. Beyond that, some experts have cited social distancing and masking requirements imposed in 2020 and 2021 to limit the spread of COVID 19. These measures, along with school closures, had the side effect of reducing exposure to influenza and RSV.
“It’s what’s being referred to as this ‘immunity gap’ that people have experienced from not having been exposed to our typical respiratory viruses for the last couple of years, combined with reintroduction to indoor gatherings, indoor venues, indoor school, and day care without any of the mitigation measures that we had in place for the last couple of years,” infectious disease expert Kristin Moffitt, MD, of Boston Children’s Hospital told NPR.
Term ‘Immunity Debt’ Sparks Controversy
Other experts have pushed back against the notion that pandemic-related public health measures are largely to blame for the RSV upsurge. Many have objected to the term “immunity debt,” a term Forbes reported on in November.
“Immunity debt is a made-up term that did not exist until last year,” pediatrician Dave Stukus, MD, wrote on Twitter. Stukus is a Professor of Clinical Pediatrics in the Division of Allergy and Immunology at Nationwide Children’s Hospital in Columbus, Ohio.
An article published by Texas Public Radio (TPR) suggests further grounds for skepticism, stating that “the immunity debt theory doesn’t seem to hold up to scrutiny.”
“That was sort of the great unmasking, and everybody got viral illnesses,” she told TPR. “Now we’re past that. We’ve already been through that. We should have some immunity from that and we’re having it again.”
She added that “the hospital is filled with babies who are less than a year of age who have RSV infection. Those children weren’t locked down in 2020.”
The story also noted that not all Americans complied with social distancing or masking guidelines.
“We’re not seeing [less viral illness in] states in the United States that were less strict compared to states that were stricter during mask mandates and things like that. All the states are being impacted,” Barton told TPR.
Perfect Storm of Demand for Clinical Laboratory Testing
Barton suggested that COVID-19 might have compromised people’s immune systems in ways that made them more susceptible to other respiratory diseases. For example, a study published in Nature Immunology, titled, “Immunological Dysfunction Persists for Eight Months following Initial Mild-to-Moderate SARS-CoV-2 Infection,” found that some patients who survived COVID-19 infection developed post-acute long COVID (LC, aka, COVID syndrome) which lasted longer than 12 weeks. And that “patients with LC had highly activated innate immune cells, lacked naive T and naive B cells, and showed elevated expression of type I IFN (IFN-β) and type III IFN (IFN-λ1) that remained persistently high at eight months after infection.”
Experts speaking to The Boston Globe said that multiple factors are likely to blame for the severity and early arrival of the RSV outbreak. Pediatric hospitalist and infectious disease specialist Chadi El Saleeby, MD, of Massachusetts General Hospital, said the severity of some cases might be tied to simultaneous infection with multiple viruses.
Clinical laboratories experienced a perfect storm of infectious disease testing demands during this tripledemic. Hopefully, with the arrival of spring and summer, that demand for lab tests will wane and allow for a return to a normal rate of traditional laboratory testing.
