Table 3.
Some elements for the rational use of complement inhibitors in kidney diseases
| Inhibition of the complement alternative pathway is a potential treatment for kidney diseases primarily driven by C3 degradation production deposition. |
| Complement alternative pathway inhibitors (factor H, factor I) with enhanced potency may represent potential therapeutic agents in complement-driven diseases. |
| Inhibition of the initial phases of the classical and lectin pathways is a potential treatment in Ig and immune complex-mediated kidney diseases. |
| C5 and C5a blockers may represent an alternative to corticosteroids as more optimal anti-inflammatory drugs (improved quality of renal remission/decreased side effects). |
| Constitutional complement alternative pathway dysregulation is only a risk factor for complement-mediated kidney diseases, and not synonymous of continuous complement activation in all carriers. |
| In Ig- and immune complex-driven kidney diseases, the primary therapeutic target is Ig or immune complexes production and not complement inhibition. |
| For complement-mediated kidney diseases, distinct complement modulators may be required during the acute and chronic phases. |
| The potential clinical benefit should clearly outweigh the infectious risk resulting from the inhibition of complement cascade components. |
| The clinical relevance of anticomplement autoantibodies for the use of complement blockers is not established, except for high-titer anti-factor H antibodies in patients with aHUS. |
| No currently available biomarker can predict response to complement blockade in kidney diseases. The design of clinical trials based, even partially, on not yet validated biomarkers may prove, at least, misleading. |
| Complement genetics may help individualize the optimal duration of anticomplement therapy in a given patient with a kidney disease (e.g., aHUS). |
| The selection of the optimal target for complement inhibition should be individualized and integrates the patient’s specific clinical characteristics, complement biological and genetic profile and kidney pathologic features. |
aHUS, atypical hemolytic uremic syndrome.