Levels of AIM protein in urine may help in tracking vasculitis treatments
Protein measures may be a noninvasive marker of AAV disease severity
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A new study from Japan found that people with ANCA-associated vasculitis (AAV) have significantly higher levels of a protein known as AIM, fully apoptosis inhibitor of macrophage, in their urine than individuals without this vasculitis type — and these levels may be a useful way to monitor an individual’s response to AAV treatment.
According to the researchers, the study findings suggest that urinary AIM levels tend to decrease after AAV patients start immunosuppressive treatments, making its measure a potential marker of both disease severity and therapy effectiveness.
“Urinary AIM levels were significantly elevated in patients with AAV and decreased following immunosuppressive therapy,” the researchers wrote. “Urinary AIM may serve as a useful non-invasive biomarker reflecting [kidney] injury and disease severity, and it may have potential utility in predicting [kidney-related] outcomes in AAV.”
An early-access version of the study, “Urinary apoptosis inhibitor of macrophage reflects renal inflammation and tubular damage in ANCA-associated vasculitis,” was published in the journal Scientific Reports. The work was funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan.
AAV is an autoimmune disease that leads to inflammation in small blood vessels, which can damage various organs. The kidneys, which are responsible for filtering blood and are therefore full of tiny blood vessels, are one of the most affected organs.
Scientists cited need for noninvasive disease markers in AAV
Kidney biopsies, an invasive procedure in which a tiny tissue sample is collected for analysis under a microscope, “play a central role in determining disease severity and guiding treatment strategies,” the researchers wrote.
However, because a kidney biopsy is not always feasible due to patient condition or associated risks, “there is a need for non-invasive biomarkers that reflect disease activity and renal [kidney] injury in AAV,” the researchers wrote.
Previous research has suggested that AIM — a protein produced mainly by tissue macrophages, a type of specialized white blood cell — generally may help the kidneys recover from acute injury, but may also contribute to the progression of certain kidney diseases.
“However, the role of AIM in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unknown,” the researchers wrote.
To fill this gap, a team led by scientists at Saitama Medical University measured AIM levels in urine samples from 57 people with AAV and 16 healthy volunteers. The patients had a mean age of 73.3, and about 60% were female. All had microscopic polyangiitis (MPA), one of the most common types of AAV.
AIM was not detectable in urine from any of the healthy volunteers, but in those with AAV, levels of this protein were significantly elevated, the researchers found. Analyses of kidney biopsies likewise showed AIM in kidney tissue from AAV patients, but not in healthy kidney tissue.
AAV patients with newly diagnosed, active disease had significantly higher urinary AIM levels than those whose disease was in remission, meaning they had no or few symptoms. No significant differences in AIM levels were found between AAV patients in remission and healthy volunteers.
Further analyses showed that urinary AIM levels were significantly associated with blood and biopsy-assessed markers of kidney damage.
The researchers noted that, consistently, analyses of urine samples collected from AAV patients over time showed that AIM levels dropped significantly after standard immunosuppressive therapy to control the disease.
Patients with higher urinary AIM levels tended to show limited improvement in [kidney] function.
Statistical analyses showed that patients whose urinary AIM levels remained elevated after treatment tended to have less improvement in markers of kidney health.
“Patients with higher urinary AIM levels tended to show limited improvement in [kidney] function,” the researchers wrote. The team noted that, while the study involved a limited number of patients, “these findings suggest that urinary AIM may have potential as a non-invasive biomarker for predicting renal outcomes in AAV.”
The urine test may be especially helpful in cases where it’s not feasible to take a kidney biopsy, the team noted.
Given the small study size and that all patients had MPA, the researchers emphasized the need for additional studies to validate the findings and AIM’s biomarker potential in AAV.
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