Kidney Week

Abstract: FR-PO896

Urine Complement Activation Products in IgA Nephropathy

Session Information

• IgA Nephropathy: Clinical, Outcomes, and Therapeutics
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Zhang, Xiaolan, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Xiaolan Zhang, MD, PhD

• Zhang, Li, The First Hospital of Jilin University, Changchun, Jilin, China

Li Zhang, MD, PhD

• Satoskar, Anjali A., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Anjali A. Satoskar, MD

• Birmingham, Daniel J., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Daniel J. Birmingham, PhD

• Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Brad H. Rovin, MD, FASN

Background

Complement activation appears to play an important mechanistic role in kidney injury in IgA Nephropathy (IgAN). In most patients with IgAN overt systemic complement consumption is not observed as measured by levels of serum complement components C3 and C4. To evaluate the possibility that complement activation occurs primarily within the kidney in IgAN we tested patient urine samples for the presence of complement activation products (CAPs), and correlated levels with the Oxford MEST-C score to determine the relationship of CAPs with kidney injury.

Methods

Serum and spot urine samples were collected from 80 IgAN patients at the time of diagnostic kidney biopsy and 29 healthy volunteers. Biopsies were classified by the Oxford MEST-C score. The CAPs assessed were fragment Ba that is generated during activation of the alternative pathway (AP), C5a, and the terminal pathway membrane attack complex C5b-9. These were measured by ELISA (C5a and C5b-9) or EIA (Ba). ANOVA, nonparametric Wilcoxon test, and multiple linear regressions were done using JMP17 pro for data analysis.

Results

Ba, C5a and C5b-9 did not correlate with serum C3 or C4 levels. Ba, C5a, and C5b-9 were 98, 44, and 2600-fold higher, respectively in the urine of IgAN patients than healthy individuals (p<0.0001 for all). C5a measured in IgAN patient serum collected at the same time as urine (n=40) showed no relationship with urine C5a. Although urine C5a and urine C5b-9 did not correlate with any MEST-C component, the level of urine Ba increased 1.6 and 6.4-fold in patients with T1 and T2 Oxford MEST-C lesions, compared to patients with T0 lesions (p=0.0005). Similarly, compared to patients with S0 lesions, Ba was 4.6-fold higher in patients with S1 lesions (p=0.0004). Interestingly Ba did not correlate with M, E, or C lesions. Ba increased with decreasing eGFR (R²=0.35, p<0.0001).

Conclusion

CAPs are found in the urine of patients with IgAN. The lack of association of simultaneously collected urine and serum C5a, and the large molecular mass of C5b-9 suggest CAPs appearing in the urine of IgAN patients are due to intra-renal complement activation. Unexpectedly, CAPs did not correlate with the inflammatory components of MEST-C score. Ba, a marker of AP activation, did however associate with chronic damage in IgAN, perhaps suggesting a role for the AP in mediating kidney fibrosis.

Funding

• Clinical Revenue Support