Sulfatide May Be Promising Biomarker for AAV-related Kidney Damage
A molecule called sulfatide is found at low levels in people with ANCA-associated vasculitis (AAV), and may indicate the presence of inflammation and a form of kidney damage that is associated with poor outcomes, a pilot study reports.
Thus, sulfatide levels may be a useful biomarker for AAV, a finding that needs to be confirmed in larger studies, researchers say.
The study, “Serum Sulfatide Levels as a Biomarker of Active Glomerular Lesion in Patients with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single Center Pilot Study,” was published in the Journal of Clinical Medicine.
AAV is a group of diseases characterized by inflammation and damage to small blood vessels, primarily affecting the kidneys and lungs.
When doctors suspect kidney involvement, patients usually undergo biopsy to determine the kind of damage affecting the organ. However, biopsies are not feasible for all patients, often due to advanced age and frailty or because patients are receiving medications that could increase the risk of bleeding.
Biomarkers that reflect disease activity and the severity of kidney damage in AAV are therefore urgently needed.
Sulfatides are molecules found on the surface of platelets, which are known to be overly active in AAV. Antibodies that target sulfatides also seem to be significantly elevated in people with AAV.
Based on these findings, researchers based at the Shinshu University Hospital in Japan wondered whether levels of sulfatide in the bloodstream of AAV patients would serve as a biomarker for kidney disease.
“To clarify the clinical importance of serum sulfatide levels in patients with AAV, we conducted a pilot study, and we compared the serum sulfatide levels between controls and patients with AAV and investigated the association between serum sulfatide levels and active kidney lesions,” the team wrote.
Blood samples were collected from 35 AAV patients and 10 healthy individuals who served as a control group. As expected, markers for compromised kidney function, inflammation, and damage to blood vessels were elevated in AAV patients but not in controls.
Analysis revealed that, compared with controls, people with AAV had significantly lower levels of sulfatide and its components in their bloodstream.
Among the 35 patients enrolled, 27 had undergone kidney biopsies. The researchers examined tissue samples under a microscope to identify different types of kidney damage, which fall into four general classes: focal, crescentic, sclerotic, and a mix of these three.
Sulfatide levels were found to be significantly lower in the crescentic class (which is associated with more severe inflammation) compared to those in other classes. These results were not seen with other AAV markers, including estimated glomerular filtration rate (eGFR) for kidney function, D-dimer for blood clotting, and soluble thrombomodulin for blood vessel damage.
C-statistics, a calculation used to evaluate the ability to predict crescentic class kidney lesions, generated a value of 0.903 for sulfatide levels. A C-statistics value above 0.9 is considered an excellent predictor.
However, while eGFR, D-dimer, and soluble thrombomodulin levels were significantly correlated with the percentage of active crescentic lesions, sulfatide levels were not.
Additional results showed that low levels of sulfatide correlated with higher levels of the inflammatory markers C-reactive protein and PTX3 in AAV patients. But there were no significant associations between sulfatide levels and clinical outcomes, including all-cause mortality, kidney failure, lung damage, nerve impairments, or blood clotting complications.
“Although no significant association between serum sulfatide levels and clinical outcomes could be detected in the current study, the reduction in serum sulfatide levels was significantly correlated with C-reactive protein and PTX3 elevation that was indicative of systemic inflammation,” the investigators concluded.
“These inflammatory responses may cause and reflect the presence of active glomerular [kidney] lesions, such as crescentic class lesions, that lead to poor renal prognosis in patients with AAV,” they added. “It is possible that a reduction in serum sulfatide levels may be a useful marker for AAV, and large-scale validation studies will be required in the future.”