Scientists have developed a new biomarker test that can noninvasively detect kidney fibrosis from a urine sample. A study published today in Science Translational Medicine reports the test could accurately differentiate between mild and severe disease, something that is not yet possible with the diagnostic methods available today.
“Noninvasive and accurate diagnosis of kidney fibrosis remains unavailable in clinics, limiting effective patient management,” write the authors of the study, led by Zhou Jiaguo, PhD, professor of pharmacology at Sun Yat-sen University in China. “Although biopsy is considered the gold standard for assessing fibrotic progression, this invasive approach is subject to sampling error and interobserver variability, which may bias the diagnosis and is improper for repeated monitoring.”
Chronic kidney disease affects approximately 12% of the global population, with rates steadily rising as the world’s population ages. Characterized by the excessive formation of scar tissue, kidney fibrosis is a hallmark of chronic kidney disease that causes the proggressive impairment of kidney function, eventually leading to end-stage renal disease that requires dialysis or transplantation.
Diagnosing kidney fibrosis at early stages can be critical for preventing irreversible damage to the kidneys. However, current diagnostic methods present some major limitations. While biopsies are invasive and difficult to accurately interpret, blood biomarker tests cannot distinguish kidney fibrosis from other kidney conditions or from fibrosis in other organs.
To circumvent these limitations, Jiaguo’s team identified two biomarkers that are specific to kidney fibrosis and can accurately differentiate this diagnosis from other related conditions. These are the transglutaminase 2 (TG2) enzyme and its substrate, lysyl oxidase–derived allysine (LysAld), which are both upregulated during the formation of fibrotic kidney tissue.
The researchers developed a fluorescent reporter that binds to LysAld in the kidney and is then cleaved by TG2, turning on its fluorescence. Higher biomarker levels result in a stronger signal, providing an indication of how advanced fibrosis is in the patient’s kidneys.
In a small cohort of 35 participants, the molecular imaging test could distinguish patients with kidney fibrosis from healthy controls with 84% sensitivity and 94% specificity. In addition, the test could differentiate mild and severe cases of fibrosis, with results confirmed with histological imaging. In contrast, traditional clinical measurements such as glomerular filtration rate, serum creatinine, and blood urea nitrogen were not able to classify patients according to the severity of the condition.
Large-scale studies will be needed to establish this novel approach as a diagnostic and prognostic. Going forward, Jiaguo and colleagues are also interested in exploring using this test to monitor disease progression over time as a potential tool to evaluate treatment response and help clinicians make critical decisions to improve patient outcomes.
“This noninvasive activatable reporter holds translational potential for early identification of renal fibrosis and patient stratification of [chronic kidney disease] to improve clinical management and patient outcome,” write the researchers. “We do not envision the probe as a standalone replacement for current standards; synergistic combinations with other biomarkers could further enhance its clinical utility.”
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