Low Albumin Levels Are Associated with Intrarenal Complement C4d Deposits in Critically Ill Patients with ANCA-Associated Renal Vasculitis

Background: Despite serum albumin levels being predictive for clinical outcome in ANCA-associated renal vasculitis (AArV), implications providing a direct link between low serum albumin levels and intrarenal lesions remain elusive. Thus, we here aimed to systematically assess the clinical relevance of low albumin levels and scrutinize clinicopathological correlations to expand our knowledge. Methods: We retrospectively enrolled biopsy-proven cases of AArV between 2015 till 2020 in a single-center observational study. Survival-curve analyses on short-term clinical recovery were performed. Correlative analyses between serum albumin levels, laboratory parameters, proteinuria levels, and histopathological lesions including tubulointerstitial immune cell infiltrates, lesions analogous to the Banff score and intrarenal complement deposition of C3c and C4d were performed. Results: Critically ill patients with serum albumin levels below the median of 2.4 g/dL featured an affected short-term clinical recovery (p=0.0082, HR: 3.6, 95% CI: 1.1-11.7). An extrarenal causation of hypoalbuminemia in the critically ill was assumed, since serum albumin levels did not correlate with the urinary marker of tubular damage (β=-0.5, p=0.07). We identified plasmacytic infiltrates to correlate with low albumin levels (β=-0.7, p=0.005) and Banff-scored interstitial inflammation (i) to be inversely correlated with albumin levels (β=-0.7, p=0.02). Intrarenal C4d deposition showed a significant correlation with low serum albumin levels in the glomerular tuft (β=-0.4, p=0.04). Conclusion: In conclusion, short-term recovery was predicted by low albumin levels in critically ill patients with AArV. We here provide evidence that low levels of serum albumin might directly affect tubulointerstitial inflammation as reflected by plasmacytic immune-cell infiltration, and intrarenal C4d complement deposition in AArV.