Biomarkers in the Management of Complement-Mediated Kidney Diseases in the Era of Complement Therapeutics

Pharmacologic complement inhibition offers a promising therapeutic strategy for several complement-mediated kidney diseases. Yet, at present, nephrologists must rely on an incomplete toolkit of histopathologic and circulating biomarkers to assess complement activity in complement-mediated kidney diseases. Our clinical capacity to characterize and monitor pathologically dysregulated complement for disease prognosis, to inform patient selection, and to evaluate therapeutic efficacy severely lags behind the growing number of complement inhibitors under development. Reliable, sensitive complement biomarkers that are suitable for clinical assessment are needed for the timely and optimal implementation of existing and upcoming therapeutics. Despite this urgent need and growing research efforts, the repertoire of clinically available complement biomarker assays has proven refractory to expansion. This is, in part, due to a myriad of practical challenges limiting the information reliably interpreted from existing complement biomarkers and hindering the translation of novel biomarkers from research settings into the clinical pathology laboratory. In this article, the authors review commonly evaluated complement biomarkers within the context of an evolving therapeutic landscape, as well as the practical challenges related to their effective application. Noteworthy, emerging biomarkers are also discussed, along with the challenges in translating robust markers of complement activity from research settings into clinical practice.