Complement-mediated renal diseases after kidney transplantation - current diagnostic and therapeutic options in de novo and recurrent diseases

Abstract

For decades, kidney diseases related to inappropriate complement activity, such as atypical hemolytic uremic syndrome and C3 glomerulopathy (a subtype of membranoproliferative glomerulonephritis), have mostly been complicated by worsened prognoses and rapid progression to end-stage renal failure. Alternative complement pathway dysregulation, whether congenital or acquired, is well-recognized as the main driver of the disease process in these patients. The list of triggers include: surgery, infection, immunologic factors, pregnancy and medications. The advent of complement activation blockade, however, revolutionized the clinical course and outcome of these diseases, rendering transplantation a viable option for patients who were previously considered as non-transplantable cases. Several less-costly therapeutic lines and likely better efficacy and safety profiles are currently underway. In view of the challenging nature of diagnosing these diseases and the long-term cost implications, a multidisciplinary approach including the nephrologist, renal pathologist and the genetic laboratory is required to help improve overall care of these patients and draw the optimum therapeutic plan.

Keywords: Complement-related diseases; Kidney transplantation; De novo; Recurrent diseases

Core tip: The recent progress in our understanding of the pathophysiology of complement-mediated diseases is gaining considerable popularity. Complement dysregulation due to inherited or acquired factors is currently the culprit mechanism. Several constitutional abnormalities usually trigger the process of recurrence, with a subsequent high rate of graft loss. The development of the terminal complement inhibitor “eculizumab” is a breakthrough in controlling abnormal complement activation. While diagnosing complement abnormalities is one challenge, treatment cost with this new agent is another major hurdle in any health care system. New lines of promising therapies are currently in the pipeline.