AB1260 LOW ALBUMIN LEVELS ARE ASSOCIATED WITH INTRARENAL COMPLEMENT C4D DEPOSITS AND PREDICT SHORT-TERM OUTCOME IN CRITICALLY ILL PATIENTS WITH ANCA-ASSOCIATED RENAL VASCULITIDES
Authors: E. Baier, I. A. Kluge, P. Korsten, S. Hakroush, B. Tampe
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Despite serum albumin levels being predictive for clinical outcome in ANCA-associated renal vasculitis, implications providing a direct link between low serum albumin levels and intrarenal lesions remain elusive. <h3>Objectives:</h3> We here aimed to systematically assess the clinical relevance of low albumin levels and scrutinize clinicopathological correlations to expand our current knowledge. <h3>Methods:</h3> We here retrospectively enrolled biopsy-proven cases of ANCA-associated renal vasculitis between 2015 till 2020 in a single-center observational study. Survival-curve analyses on long-term renal survival and 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. <h3>Results:</h3> We here show that hypoalbuminemia below the median of 2.4 g/dL impairs long-term renal survival especially in MPO-positive ANCA-associated renal vasculitis (<i>p</i> = 0.006, HR: 5.0, 95% CI: 1.2-21.5), while short-term clinical recovery particularly in critically ill patients is negatively affected by low serum albumin levels (<i>p=0.0082</i>, HR: 3.6, 95% CI: 1.1-11.7). Low albumin levels are associated with the urinary marker of tubular damage in the total cohort (<i>β</i> = -0.5, <i>p</i> = 0.01), PR3-ANCA (<i>β</i> = -0.5, <i>p</i> = 0.04) and MPO-ANCA (<i>p</i> = 0.002, <i>β</i> = -0.8), but not in critically ill patients (<i>β</i> = -0.5, <i>p</i> = 0.07) implying hypoalbuminemia to occur by extrarenal causation in the state of critical illness. We identified plasmacytic infiltrates to correlate with low albumin levels in the total cohort (<i>β</i> = -0.6, <i>p</i> = 0.004) and in the subgroup of critically ill patients (<i>β</i> = -0.7, <i>p</i> = 0.005). Banff-scored interstitial inflammation (<i>i</i>) was further observed to inversely correlate with albumin levels (<i>β</i> = -0.7, <i>p</i> = 0.02). Intrarenal C4d deposition showed a significant correlation with low serum albumin levels in the glomerular tuft (<i>β</i> = -0.4, <i>p</i> = 0.04) and in interstitial arteries (<i>β</i> = -0.7, <i>p</i> = 0.01). <h3>Conclusion:</h3> In conclusion, long-term renal outcome is significantly affected by low serum albumin levels especially in the setting of MPO-ANCA seropositivity. By contrast, short-term recovery was predicted by low albumin levels in critically ill patients with ANCA-associated renal vasculitis. 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 ANCA-associated renal vasculitis. <h3>REFERENCES:</h3> [1] Berden, A. E., F. Ferrario, E. C. Hagen, D. R. Jayne, J. C. Jennette, K. Joh, I. Neumann, L. H. Noel, C. D. Pusey, R. Waldherr, J. A. Bruijn, and I. M. Bajema. "Histopathologic Classification of Anca-Associated Glomerulonephritis." <i>J Am Soc Nephrol</i> 21, no. 10 (2010): 1628-36. [2] Flossmann, O., A. Berden, K. de Groot, C. Hagen, L. Harper, C. Heijl, P. Hoglund, D. Jayne, R. Luqmani, A. Mahr, C. Mukhtyar, C. Pusey, N. Rasmussen, C. Stegeman, M. Walsh, K. Westman, and Group European Vasculitis Study. "Long-Term Patient Survival in Anca-Associated Vasculitis." <i>Ann Rheum Dis</i> 70, no. 3 (2011): 488-94. [3] Weidner, S., S. Geuss, S. Hafezi-Rachti, A. Wonka, and H. D. Rupprecht. "Anca-Associated Vasculitis with Renal Involvement: An Outcome Analysis." <i>Nephrol Dial Transplant</i> 19, no. 6 (2004): 1403-11. [4] Hakroush, S., D. Tampe, P. Strobel, P. Korsten, and B. Tampe. "Comparative Histological Subtyping of Immune Cell Infiltrates in Mpo-Anca and Pr3-Anca Glomerulonephritis." <i>Front Immunol</i> 12 (2021): 737708. [5] Ge, Y., G. Yang, X. Yu, B. Sun, B. Zhang, Y. Yuan, M. Zeng, N. Wang, H. Mao, and C. Xing. "Outcome Predictors of Biopsy-Proven Myeloperoxidase-Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis." <i>Front Immunol</i> 11 (2020): 607261. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>