No compliment for complement: Kidney biopsies of patients with malignant nephrosclerosis show no complement activation

ABSTRACT The complement system represents an ancient part of innate immunity and is comprised of multiple serum proteins. In several pathological conditions, including atypical hemolytic syndrome (aHUS), complement activation is contributing to disease progression. Therefore, pharmacological targeting of complement is a viable therapeutic strategy in this population. Recent data suggest complement activation in patients suffering from malignant hypertension and stenosing arteriosclerosis also called malignant nephrosclerosis (MNS). Since MNS and aHUS also share histopathological similarities therapeutic complement inhibition became a discussion in MNS. To eliminate the pitfall of confusing complement trapping with activation in the kidney we used the proximity ligation assay to detect, visualize and quantify assembled complement convertases of the different pathways in renal tissue diagnosed with MNS or aHUS. We compared them to a control group of patients presenting with thin basement membrane syndrome (TBMD). Activation of the alternative and the classical pathways were examined by glomerular and vascular quantification of C3b/Bb and C4b/C2b, respectively. We found an overactivation of the alternative pathway only in patients suffering from aHUS, while complement activation was not altered in MNS when compared with TBMD. Thus our results cannot contribute to the hypothesis that complement inhibition may be an efficient therapeutic strategy for patients presenting end-organ damage due to stenosing arteriosclerosis. The use of complement inhibition in these patients cannot be recommended.