Abstract: TH-PO108

Urinary Excretion of C5a in Membranous Nephropathy

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Ayoub, Isabelle, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Birmingham, Daniel J., Ohio State University, Columbus, Alabama, United States
  • Nelson, Jessica M., Ohio State Wexner Medical Center, Columbus, Ohio, United States
  • Hebert, Lee A., Ohio State University Medical Center, Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Background

Using proteomic analysis we previously showed that glomeruli from patients with membranous nephropathy (MN) express increased levels of complement components C3 and C4 and decreased levels of the complement receptor CR1 compared to glomeruli from healthy kidneys. Here we measured complement component C5a in the urine of MN patients as a non-invasive surrogate of intra-renal complement activation.

Methods

Urine samples were collected at the time of first kidney biopsy of patients with active MN (n=13). These patients had primary MN as suggested by dominant (n=5) or co-dominant (n=6) IgG4 glomerular immunofluorescence. Two patients only had IgG1 glomerular immunofluorescence, usually seen in secondary MN, but no underlying etiology was found in either case, so they were treated as primary MN. Urine C5a levels were measured by a sandwich ELISA.

Results

Urine protein to creatinine ratios (uPCR) in this group of MN patients ranged from 2.2-11 g/g with a median of 4 g/g. Urine C5a levels were undetectable in 2 two patients. The median value for the group was 4 ng/mg urine creatinine with a range of 0-11 ng/mg. Patients with Ig4 dominant or co-dominant MN had a higher level of C5a (5.1±3.3 ng/mg) than patients who were IgG1 dominant (1.3±1.8). C5a levels correlated with spot uPCR (r=0.68, p= 0.01), however the correlation was mainly driven by those with heaviest proteinuria.

Conclusion

In immunologically active primary MN, C5a is present in the majority of urine samples. In secondary (IgG1-dominant) MN C5a levels were much lower than in primary MN, but this is difficult to interpret due to small sample size. The presence or absence of urinary C5a could be useful in differentiating immunologically active proteinuric patients with an historic diagnosis of MN from proteinuria driven by hemodynamic or other factors, facilitating decisions regarding immunosuppressive therapy without repeating kidney biopsy. The relationship between urinary C5a and anti-PLA2R levels remains to be determined.