Eculizumab in Primary MPGN

EVALUATING THE MORPHOFUNCTIONAL EFFECTS OF ECULIZUMAB THERAPY IN PRIMARY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS: A PILOT, SINGLE ARM STUDY IN TEN PATIENTS WITH PERSISTENT HEAVY PROTEINURIA

Membranoproliferative glomerulonephritis (MPGN) is the third or fourth leading cause of end stage renal disease among the primary glomerulonephritis. Hyperactivation of the alternative complement pathway and familial forms for all types of MPGN have been reported suggesting that genetic abnormalities may play a predisposing role to the disease. In recent case reports Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex ,is a safe and effective therapy.

Inclusion Criteria:

• Biopsy-proven primary MPGN
• Creatinine clearance >20 ml/min per 1.73m2
• 24-hour proteinuria persistently exceeding 3,5g in adults or exceeding 40mg/h/m2 in children (or exceeding 2mg protein/mg creatinine in children spot urine samples)
• Persistently low C3 levels in at least two consecutive evaluations
• Persistently high sC5b9 levels (>1000 ng/ml) in at least two previous consecutive evaluations
• Written informed consent (by parents or tutors if underage)

Exclusion Criteria:

• Age ≥75 years
• Secondary MPGN (evidence of infection, immunological disease including vasculitis, systemic diseases and proliferative disorders)
• Evidence at kidney biopsy evaluation of severe chronic histological changes that very unlikely could benefit of eculizumab therapy
• Concomitant steroid or immunosuppressive therapy for immuno-mediated disease
• Pregnancy or lactating
• Childbearing potential without effective contraception
• Any clinically relevant condition that might affect completion of the study participation and/or confound study results
• Inability to understand the potential risks and benefits of the study
• Legal incapacity