2 proteins in urine flag kidney failure risk in AAV early on, new study finds
Noninvasive testing could help prognosis, assess treatment response in patients
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Measuring urine levels of two proteins in people with ANCA-associated vasculitis (AAV) and kidney involvement independently predicted their risk of progression to kidney failure, according to a new study from China.
The researchers found that noninvasive testing of trehalase and neutrophil gelatinase-associated lipocalin (NGAL), two highly sensitive urinary biomarkers, flagged the risk of end-stage kidney disease early on among the 88 patients in the study. Combining the two markers slightly improved risk prediction, the team also noted.
Overall, these findings suggest that urine levels of NGAL and trehalase “have potential clinical utility and may complement conventional indicators to enable early risk identification and individualized management in AAV patients,” the researchers wrote.
The study, “Urinary NGAL and trehalase predict end-stage kidney disease in ANCA-associated vasculitis: a prospective cohort study,” was published in the journal Renal Failure.
AAV refers to a group of autoimmune diseases characterized by inflammation in small blood vessels. In most cases, AAV is caused by self-reactive antibodies, called ANCAs, that target proteins produced by neutrophils, a type of immune cell.
The disease can affect several organs, most commonly the kidneys and lungs. When it affects the kidneys, it can cause rapidly worsening kidney damage and, in some cases, progress to kidney failure, when the kidneys no longer work well enough to meet the body’s needs.
Kidney recovery can vary widely after AAV treatment
Treatment for AAV often involves strong immunosuppressive therapies. While these treatments have improved outcomes, kidney recovery can vary widely among patients.
Clinicians now use blood and urine tests, along with kidney biopsy findings, to help assess prognosis and treatment response in AAV patients with kidney involvement. However, those first two measures can lack precision, and kidney biopsies are invasive procedures unsuitable for routine monitoring.
As such, researchers are seeking noninvasive biomarkers that can help identify patients at higher risk of kidney function decline earlier and to monitor disease activity over time.
Previous studies have suggested that several urine markers may reflect kidney injury or inflammation in AAV. These include beta-catenin, which may be linked to active kidney lesions, and interleukin-18. Trehalase, and NGAL, which are associated with injury to the tiny tubes in the kidneys, are other markers that have been suggested.
In this study, a team of researchers in China assessed whether these four urine markers could predict long-term kidney outcomes, including progression to kidney failure.
The participants’ mean age was 52.75, and there were slightly more men than women. All were followed for a median of 27 months, or more than two years, at a single Chinese center. Most patients were positive for ANCAs against myeloperoxidase (MPO), one of the most common targets of these antibodies.
Slightly more than a quarter of patients required hemodialysis, a kidney replacement procedure, at diagnosis. During follow-up, nearly three-quarters progressed to kidney failure and required kidney replacement.
At diagnosis, those who progressed to kidney failure had worse kidney function and were more likely to need hemodialysis, the data showed.
All four urine biomarkers measured — beta-catenin, interleukin-18, trehalase, and NGAL — were significantly higher in patients who progressed to kidney failure. However, after adjusting for potential influencing factors, including dialysis status and ANCA type, only higher urinary trehalase and NGAL levels remained consistently and independently associated with a greater risk of kidney failure, according to the researchers.
The team determined that cutoff values of 1.17 nanograms per milliliter (ng/mL) for trehalase and 11.7 ng/mL for NGAL helped stratify kidney failure risk among participants.
Those with higher urine trehalase levels had more than double the risk of progressing to kidney failure compared with those with lower levels. Higher urine NGAL levels were associated with a nearly fourfold higher risk.
[These findings suggest urine NGAL and trehalase levels] are independent predictors of progression to [kidney failure] in patients with AAV with kidney involvement, and their combination improves the accuracy of risk stratification.
The markers’ ability to discriminate participants who progressed to kidney failure from those who didn’t was evaluated with the Area Under the Curve (AUC), a test whose values range from zero to one; the higher the value, the greater the discriminative potential.
Trehalase had an AUC of 0.857, while NGAL had an AUC of 0.852. Combining trehalase and NGAL improved performance slightly, with an AUC of 0.869.
Analyses of kidney survival — meaning no kidney failure or need for hemodialysis — showed clear differences based on these markers. Participants with higher trehalase had a median kidney survival of eight months, compared with 72 months, or about six years, among those with lower trehalase. Patients with higher NGAL had a median kidney survival of three months, compared with 48 months, or four years, in the lower NGAL group.
Also, those with high levels of both markers had the fastest kidney function decline, particularly within the first two years. By the end of follow-up, all participants in the highest-risk group had progressed to kidney failure, the researchers noted.
The scientists also looked separately at patients who did not require hemodialysis at diagnosis to make sure the findings were not driven only by those with the most severe kidney failure at diagnosis. In this group, trehalase and NGAL still independently predicted progression to kidney failure.
Overall, these findings suggest urine NGAL and trehalase levels “are independent predictors of progression to [kidney failure] in patients with AAV with kidney involvement, and their combination improves the accuracy of risk stratification,” the researchers wrote.
However, to validate their predictive performance and clinical applicability future “multicenter, large-sample prospective studies” are required, the team concluded.
