#6881 elevated levels of the c5b9 terminal complement complex in patients receiving renal replacement therapy

Abstract Background and Aims The complement cascade and its inhibitors play an important role in health and disease. Complement activation represents a key pathogenic mechanism underlying inflammatory diseases affecting the kidney. The study aimed to investigate the C5b9 system in renal biopsies, where we stained all obtained kidney biopsies from the year 2017 (n = 256). Method Antibody staining against terminal C5b9 was performed, and a C5b9 score for each glomerulus (n = 1942) was generated based on automated image analysis. Mean scores for the interstitium, tubules and blood vessels, and whole biopsy sections were also calculated. Results Globally and segmentally, sclerosed areas in glomeruli stained much stronger than their non-sclerosed glomerular counterparts. The results were linked with Renal Replacement Therapy (RRT) status and clinical data from the Norwegian Kidney Biopsy Registry. The study's main findings were that elevated levels of C5b9 were present in patients on RRT in glomeruli, blood vessels and whole section staining. Fibrillar glomerulopathy and Membranous Glomerulonephritis had the highest C5b9 scores, while glomeruli from Hypertensive Nephrosclerosis were represented with a low score. C5b9 scores correlated weakly or non-significantly with clinical variables like age, blood pressure and eGFR. The degree of fibrosis showed an associated positive correlation to C5b-9 staining intensities. Additionally, patients with an elevated C5b9 score (from the 50th percentile and above) showed a significantly elevated risk of receiving RRT within 60 months of biopsy. Conclusion C5b9 levels were significantly elevated in sclerotic glomeruli as well as in patients receiving RRT. A weak correlation between C5b9 scores and clinical variables for renal function suggest that the C5b9 complement system may be an independent effector in CKD.