Elevated serum uric acid levels correlate with decreased complement C3 serum levels: implications of immunometabolism in critically ill patients with ANCA-associated renal vasculitis
BAIER E. 1, KLUGE I. 2, HAKROUSH S. 2, TAMPE B. 1
1 Department of Nephrology and Rheumatology, University Medical Center Goettingen, Goettingen, Germany; 2 Department of Pathology, Goettingen, Germany
Elevated levels of serum uric acid (SUA), the final metabolite of purine nucleotide degradation, independently predict progression to end-stage renal disease (ESRD) in ANCA-associated renal vasculitis. Still, clinicopathological correlations of SUA levels and especially inflammatory parameters lack further specificity. We therefore aimed to systematically analyze the correlative pattern of SUA levels with laboratory and histopathological lesions in hospitalized patients with biopsy-proven ANCA-associated renal vasculitis.
A total number of 34 patients with biopsy-proven ANCA-associated renal vasculitis between 2015 and 2020 were retrospectively enrolled in a single-center observational study. Assessment of clinical and laboratory data was performed. Renal biopsies were evaluated for glomerular lesions, Banff-score analogous lesions and deposition of complement C3c and C4d. Correlative analyses were performed by means of Pearson’s/ Spearman’s correlation and multivariable regression analyses in three subgroups: critically ill (CI) patients (n=19), MPO-ANCA (n=21) and PR3-ANCA (n=13).
Enrolled patients featured a median age of 69 years and SUA levels averaged out at 6.8 ± 1.7 mg/dL. An inverse correlation of SUA levels and complement C3 levels was identified as the strongest association (r=-0.6; β=-0.601, p=0.005) in the total cohort and in the CI subgroup (r=-0.7; β=-0.577, p=0.01). Significant associations of SUA levels and tubulitis in scarred cortex was identified in the total cohort (r=0.5; β=0.494, p=0.008), CI subgroup (r=0.4; β=0.489, p=0.04) and MPO-ANCA (r=0.6; β=0.533, p=0.019). SUA levels correlated with C4d complement deposition in venules in the total cohort (r=0.4; β=0.500, p=0.007). In PR3-ANCA, interstitial fibrosis was observed to be the strongest association with SUA levels (r=0.5; β=0.626, p=0.022).
We here provide evidence that serum uric acid is independently implied in systemic complement activation, especially in critically ill patients with ANCA-associated renal vasculitis. Hence, we expand our current understanding of the role serum uric acid in the complement system in autoimmune kidney diseases.