Göttingen, Germany – In individuals with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), uric acid (UA) metabolism might be involved in activation of the complement system and thus serve as a contributory factor in the disease course, according to findings from a retrospective study published in the International Journal of Molecular Sciences.
Although it has been well recognized that involvement of the complement system plays a major role in the pathogenesis of AAV, the immunometabolic implications, particularly with respect to UA concentrations, remain unclear. AAV is a severe autoimmune disorder that may present as one of the following:
- Granulomatosis with polyangiitis (GPA)
- Microscopic polyangiitis (MPA)
- Eosinophilic granulomatosis with polyangiitis (EGPA)
Among patients with AAV, renal involvement is a key predictor or overall mortality. In fact, the term “ANCA-associated renal vasculitis” denotes a kidney-focused view mainly of patients with GPA and MPA who exhibit biopsy-proven kidney injury. In individuals with AAV and renal involvement, the state of increased UA levels, known as hyperuricemia, has been shown to be an independent risk factor for progression to end-stage kidney disease.
It has been demonstrated that around two-thirds of UA metabolites undergo renal elimination. In patients with GPA and MPA, decreased kidney function has been associated with hyperuricemia. The researchers of the current analysis sought to systematically evaluate clinicopathologic associations of serum UA concentrations with laboratory, clinical, and histopathologic parameters in AAV.
Between 2015 and 2020, thirty-four individuals who had biopsy-proven AAV with renal involvement were enrolled in the present study. The median patient age was 69 years. Overall, 14 of the participants were female and 20 were male.
Among the patients, serum UA levels were associated with clinical and histopathologic features. The participants were divided into 3 subgroups:
- Critically ill subgroup: n=19
- Myeloperoxidase (MPO)-ANCA subgroup: n=21
- Proteinase 3-ANCA subgroup: n=13
Results of the study revealed that in the total study cohort and in the critically ill subgroup, an inverse statistically significant association was reported between serum UA concentrations and complement C3 levels (P =.005 and <.001, respectively). Moreover, intrarenal complement C4d deposition in venules was significantly associated with serum UA levels in the total cohort and in the critically ill subgroup (P =.007 and =.016, respectively).
There were significant associations reported between serum UA concentrations and tubulitis in areas of scarred cortex in the total cohort (P =.008), the critically ill subgroup (P =.034), and the MPO-ANCA subgroup (P =.029). Interstitial fibrosis had the strongest relationship with serum UA concentrations (P =.022).
“Our observations broaden our current understanding of contributory metabolic factors that influence the initial disease course in ANCA-associated renal vasculitis,” the investigators concluded.
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Dr. Eva Baier