Kidney Diseases Associated with Alternative Complement Pathway Dysregulation and Potential Treatment Options

摘要

Atypical hemolytic uremic syndrome and C3 glomerulopathy (dense deposit disease and C3 glomerulonephritis) are characterized inappropriate activation of the alternative complement pathway (AP). Genetic mutations affecting the AP regulating proteins (complement factor H, I, membrane co-factor protein, complement factor H related proteins) and triggers (such as infection, surgery, pregnancy, and autoimmune disease flares) result in the clinical manifestation of these diseases. A decade ago prognosis of these disease states was quite poor with the majority of patients developing end-stage renal disease. Furthermore, renal transplantation in these conditions was associated with poor outcomes due to graft loss to recurrent disease. Recent advances in targeted complement inhibitor therapy resulted in significant improvement in disease remission, renal recovery, health-related quality of life and allograft survival.