The complement system, an arm of the innate immune system plays a critical role in both health and disease. The complement system is highly complex with dual possibilities, helping or hurting the host, depending on the location and local microenvironment. The traditionally known functions of complement include surveillance, pathogen recognition, immune complex trafficking, processing and pathogen elimination. The noncanonical functions of the complement system include their roles in development, differentiation, local homeostasis and other cellular functions. Complement proteins are present in both, the plasma and on the membranes. Complement activation occurs both extra‐ and intracellularly, which leads to considerable pleiotropy in their activity. In order to design more desirable and effective therapies, it is important to understand the different functions of complement, and its location‐based and tissue‐specific responses. This manuscript will provide a brief overview into the complex nature of the complement cascade, outlining some of their complement‐independent functions, their effects at different locale, and their implication in disease settings.

Background Broad organ acceptance can increase early kidney transplantation (KTX) within <1‐year of dialysis initiation while improving access inequity. Methods Single‐center data of adult isolated deceased‐donor KTX recipients between 2013 and 2020 were stratified into three 2.5‐year periods before‐, early after‐, and late after our center's deceased‐donor organ acceptance practice change, excluding a 6‐month implementation period. Outcomes were assessed within five recipient subgroups based on demographic and clinical characteristics. Results Of 704 recipients, the frequency of early KTX was 22% pre‐change, 36% early post‐change, and 34% late post‐change. Given similar post‐change frequencies of early KTX, post‐change eras were combined to improve analytic power of subgroup analyses. After the organ acceptance practice change (vs. pre‐change), the likelihood of early KTX increased variably within historically underserved groups, including recipients who were older (37%–39%, p = .859), Black (10%–21%, p = .136), female (21%–37%, p = .034), diabetic (13%–32%, p = .010), and BMI≥35 kg/m2 (20%–34%, p = .007). Despite the practice change, Black recipients continued to experience less early KTX compared to non‐Black recipients. The likelihood of delayed graft function was significantly increased (p < .001), and 1‐year creatinine was significantly higher (p < .001) post‐practice change, but between‐era risk‐adjusted death‐censored graft survival was similar. Conclusions Transition to broader donor acceptance was associated with more early KTXs among historically underserved patient subgroups. However, the effect was non‐significant among Black recipients, suggesting the need for additional strategies to impact early transplant access for this population. Studies of broad organ acceptance are needed to examine both access and outcomes.