Abstract: FR-PO0678
Evaluation of the Complement System in the Pathogenesis and Prognosis of Normocomplementemic Glomerulopathies
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - ANCA/FSGS
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Eid, Karina Zanchetta Cardoso Eid / KZCE, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, SP, Brazil
- Zen, Renata De cassia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, SP, Brazil
- Dias, Cristiane B., Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, SP, Brazil
Background
Complement activation contributes to kidney injury even in glomerular diseases without overt systemic complement consumption. We assessed serum levels of Factor H, urinary levels of Factor H and C4d, and histological expression of CFHR2, the latter modulates factor H dependent regulation and promote local alternative pathway dysregulation.
Methods
We studied patients with IgA nephropathy, membranous nephropathy, and ANCA-associated/pauci-immune glomerulonephritis.
Results
Serum and urine analysis revealed no differences among glomerular diseases regarding serum and urine factor H, nor were there any correlations with the outcome of dialysis (Table 1). In contrast, urinary C4d corrected for urinary creatinine showed a significant positive correlation with the protein-to-creatinine ratio at diagnosis (Spearman r=0.69; p<0.0001), and a negative correlation with serum albumin at diagnosis (Spearman r=-0.47, p=0.0081). There was also no correlation with the dialysis outcome. Median glomerular CFHR2 were less positivity in ANCA-associated/pauci-immune disease, 14.4%, than IgA nephropathy, 34.8%, and n membranous nephropathy, 49.2%, p< 0.0001.
Conclusion
It is not possible to confirm the involvement of a single complement pathway in these diseases; however, there is evidence of involvement of the lectin and alternative pathways, as indicated by the presence of urinary C4d and increased tissue expression of CFHR2 in IgA nephropathy and membranous nephropathy.
Table 1: Baseline clinical and laboratory characteristics of the study population
| NIgA (n=13) | NM (n=14) | ANCA (n=4) | p | |
| Age(years) | 38.31 ± 14.0 | 45.93 ± 17.93 | 61.75 ± 11.30 | 0.04 |
| Male (%) | 46.2 | 50 | 25 | 0.0006 |
| Proteinuria (g/day) | 1.51(0.62-2.51) | 5.16±2.57 | 2.00 ± 1.16 | 0.0015 |
| Serum albumin (g/dl) | 3.57 ± 0.88 | 2.27 ± 0.60 | 3.27 ± 0.45 | 0.0002 |
| Serum creatinin (mg/dl) | 1.48(0.78-2.75) | 0.78(0.50-2.30) | 3.79 ±1.41 | 0.01 |
| GFR (ml/min/1.73m2) | 56(29.50-94.50) | 93(30.75-131.80) | 15.75 ± 6.94 | 0.02 |
| Serum C3 (mg/dl) | 117.70 ± 16.52 | 116(108-151.3) | 87.50 ± 17.41 | 0.02 |
| Serum C4 (mg/dl) | 27.80 ± 8.14 | 29.30(20.88-44.03) | 22.73 ± 6.51 | 0.31 |
| Serum Factor H (mg/l) | 169.80 (78.28- 623.80) | 121 (73-245) | 175.60 (99.49-661.50) | 0.55 |
| Urinary Factor H (mg/mg creatinin) | 17.20 (7.36-173.10) | 44.74(18.78-241.30) | 27.05(11.75-30.32) | 0.42 |
| Urinary C4d (ng/mg creatinin) | 99.51±182.40 | 154.9(6.06-426.30) | 81.28±99.45 | 0.08 |
NM- membranous nephropathy; NIgA- IgA nephropathy mean ± standard deviation; median (interquartile range)