Complement and the kidney in the setting of Shiga-toxin hemolytic uremic syndrome, organ transplantation, and C3 glomerulonephritis

Keir, L. S.; Langman, C. B.

Transfus Apher Sci. 2016 May 9; 54(2):203-11

Abstract

OBJECTIVES: To review the role of complement in glomerular pathologies focusing on thrombotic microangiopathies (TMA) caused by Shiga toxin (Stx) and organ transplantation associated hemolytic uremic syndrome (HUS) as well as C3 glomerulopathy (C3G). METHODS: Examination of literature discussing TMA associated with Stx HUS, transplantation related HUS and C3G. RESULTS: There is an emerging role for complement biology in the renal glomerulus where its inappropriate over-activation is integral to several diseases. Stx HUS patients show evidence of complement activation and the toxin itself can activate complement and inhibit its normal regulation. However, therapeutic complement blockade has not yet proven effective in all circumstances. This may be partly related to late use and a clinical trial could be warranted. Organ transplantation associated HUS has carried a poor prognosis. While case reports supporting the use of complement inhibition exist, there has not been a formal trial. Complement activation in C3G is established but again treatment with complement inhibition has failed to be uniformly beneficial. Here, too, a clinical trial may help determine which subgroup of patients should be treated with these agents. CONCLUSION: Complement plays an important role in the glomerulus but more work is needed to fully understand how it contributes to normal function and pathology. This will help direct appropriate therapy in these diseases.

Read More on PubMed