March 22, 2023 | A smartphone-based app and test kit for lupus nephritis, a frequent and serious complication of systemic lupus erythematosus, may start making its way to neighborhood CVS and Walgreens stores in another few years. The urine test has been shown to detect the protein ALCAM (activated leukocyte cell adhesion molecule) to distinguish lupus patients with and without the condition with 86% accuracy in multiple cohorts, according to Chandra Mohan, M.D., Ph.D., professor of biomedical engineering at the University of Houston where the research is underway.
In 2020, ALCAM was one of the top hits of a comprehensive screen of roughly 1,000 urine proteins found uniquely in lupus nephritis patients, Mohan says. Other, better markers also may well emerge over the next couple of years as development efforts continue.
Researchers will be collaborating with a Houston-based startup, The Predict Health, to mass produce the test to get the cost on par with a home pregnancy test, which is based on the same lateral flow assay technology. They also aim to make it more user-friendly, meaning producing results in a few minutes.
For research published recently in Frontiers in Immunology (DOI: 10.3389/fimmu.2022.1044743), the team used lateral flow immunoassays where the reporters were nanophosphor-based persistent luminescence nanoparticles that emit intense visible light after excitation, based on earlier pioneering work on phosphor-based reporters by co-senior author Richard Willson. These glow-in-the-dark particles—based on the same principles as stars pasted on the ceiling of children’s bedrooms—are credited with improving the test’s sensitivity.
The glowing nanoparticles made of phosphors are a product of prior work done in Willson’s lab and now a commercial offering of Clip Health, founded by two of his students. Willson has separately used the technology to create an at-home COVID test where a small plastic box excludes light, in lieu of a dark room, to let a smartphone camera do the reading.
An invasive kidney biopsy is the current gold standard for diagnosing lupus nephritis, which eventually strikes about 60% of adults and 80% of children with lupus, says Mohan, who went to medical school in Singapore before coming to the U.S. three decades ago to become a lupus researcher. But the biopsy cannot be serially repeated due to the morbidity risks, notably bleeding.
African Americans and Hispanics are at higher risk of lupus-associated renal disease and Asian populations are also particularly vulnerable, he continues. “Most patients never know when the kidney is becoming inflamed because inflammation in the early stages is silent. By the time symptoms set in and patients get into the physician’s office it could be several months after inflammation onset.”
The goal here is to give patients a means to regularly monitor their renal health at home to help catch inflammation in the earliest stages, so treatment can begin sooner and, consequently, “the outcome will be significantly better,” says Mohan.
Before the test gets to pharmacy store shelves, it will need the approval of the U.S. Food and Drug Administration. The most immediate step is to do field testing of the point-of-care platform in hospitals, and two have already agreed to be investigative sites, reports Mohan. Those trials are expected to begin in 2024.
In the interim, “be proactive in monitoring the disease,” is his advice to lupus patients. “Do not wait for symptoms to set in and then go see the physician.” Nephritis flares are hard to recognize because their symptoms often masquerade as something else, such as a cold or the flu or run-of-the-mill fatigue, he explains.
This has been demonstrated scientifically after examining both sample types from patients with lupus. “Urine is always more predictive, and we have extrapolated that to other diseases as well,” says Mohan. The data shows, for example, that the stool is the best place to find biomarkers of inflammatory bowel disease, while urine would be the most telling biofluid in someone with renal disease.
The take-home message for researchers in this area, Mohan adds, is “the closer you get to the tissue of inflammation, the higher the chance that you will observe highly accurate biomarkers.” In the case of kidney disease, urine is a better place to look than in the blood.
This has been demonstrated scientifically after examining both sample types from patients with lupus. “Urine is always more predictive, and we have extrapolated that to other diseases as well,” says Mohan.