Continuing C3 breakdown after bilateral nephrectomy in patients with membrano-proliferative glomerulonephritis

Area of Science:

• Nephrology
• Immunology
• Complement System

Background:

• Membranoproliferative glomerulonephritis (MPGN) is associated with complement system dysregulation.
• Low C3 levels and presence of C3 nephritic factor (C3NeF) are observed in some MPGN patients.

Purpose of the Study:

• To investigate the source of C3 breakdown and the role of C3NeF in MPGN patients undergoing nephrectomy and awaiting transplantation.
• To determine if C3 breakdown is renal or extrarenal.

Main Methods:

• Serial measurement of complement components (C3, C4, C5) and C3NeF in two MPGN patients.
• Analysis of serum C3 breakdown product (alpha 2D) levels.
• Monitoring during anephric period (peritoneal dialysis) and post-renal transplantation.

Main Results:

• Patients exhibited low C3 and high alpha 2D before nephrectomy, persisting during the anephric period.
• Post-transplantation, C3 levels normalized and alpha 2D disappeared.
• C3NeF was detected in both patients; its levels varied but did not correlate with C3 or alpha 2D.
• C4 and C5 levels were normal or elevated and unrelated to C3 levels.

Conclusions:

• Low C3 levels in these MPGN patients resulted from excessive complement C3 breakdown, not reduced synthesis.
• C3NeF, reacting with a cofactor to form C3 lytic nephritic factor (C3LyNeF), likely mediated the C3 cleavage.
• The extrarenal origin of C3 breakdown and the extrarenal source of C3NeF and cofactor were indicated by stable levels during the anephric period.