Infection risk mitigation with complement inhibitors in kidney disease

Area of Science:

• Nephrology
• Immunology
• Infectious Disease

Background:

• Complement inhibitors are increasingly used for kidney diseases.
• Therapeutic complement blockade poses an infection risk, particularly against encapsulated bacteria.
• Structured prevention strategies are essential for patient safety.

Purpose of the Study:

• To review complement biology and infection risks associated with complement inhibitors in kidney diseases.
• To propose a pragmatic framework for mitigating infection risk in patients treated with complement inhibitors.
• To inform clinical practice as complement therapies expand.

Main Methods:

• Narrative review integrating complement biology, kidney trial evidence, pharmacovigilance data, and public health recommendations.
• Analysis of target-specific infectious risk patterns based on complement functions (C3b opsonisation, C3a/C5a inflammation, MAC formation).

Main Results:

• Terminal C5 inhibition (eculizumab, ravulizumab) shows a consistent risk of invasive meningococcal disease, even with vaccination.
• Inhibition at C3/C3b or alternative pathway shows no consistent encapsulated-pathogen signal in Phase 3 trials, but long-term data is limited.
• Infection risk is target-dependent and amplified by CKD, dialysis, transplantation, and immunosuppression.

Conclusions:

• Effective prevention requires target-adapted vaccination, potential antimicrobial prophylaxis, and patient education.
• Vaccination alone does not eliminate infection risk, especially with C5 blockade.
• Mechanism-informed, kidney-specific prevention strategies are crucial for safe use of complement inhibitors.