New Boundaries for Complement in Renal Disease

Toll-Like Receptors and Danger Signaling in Kidney Injury

“…Kidneys respond to environmental perturbagens by activating their own defense mechanisms such as cellular proliferation 7,8 and the release of complement components, 9 antimicrobial defensins, 10 or matrix components into extracellular spaces. 11 In addition, kidneys engage extrinsic help for controlling danger by sending dendritic cells to regional lymph nodes 12 or releasing cytokines and chemokines that alert and recruit the professional danger controllers of the immune system.…”

C5b-9 does not mediate tubulointerstitial injury in experimental acute glomerular disease characterized by selective proteinuria

“…So far, only a few studies in humans have compared the pattern of complement expression in minimal change disease with other types of glomerulonephritides [6] . Based on clinical experience from renal biopsy samples minimal change disease is not believed to mediated by C5b9 [34] . Furthermore, despite the detection of properdin on the apical brush border of proximal tubules in rats with PON [28] , the urinary excretion of C5b9 in human minimal change disease is low [6,33] .…”

“…These observations suggest that proteinuria per se is not a prerequisite for intraluminal C5b9 formation, and that it may not mediate tubulointerstitial damage in glomerular disease (as in minimal change disease) characterized by highly selective proteinuria [34,35] . To test this hypothesis in the preclinical setting, proteinoverload nephropathy (PON) was induced in rats deficient or sufficient in complement C6.…”

In vivo therapeutic efficacy of intra-renal CD40 silencing in a model of humoral acute rejection

“…It is well known that intra-graft Local silencing of CD40 changes rejection pattern E Ripoll et al synthesis of complement can have a profound effect on acute allograft rejection. 23,24 Alloantibody-mediated humoral rejection results from high-titter de novo DSA formation, leading to a high risk of early graft loss. 1 Our model was previously described as 'humoral-like' as it displays vascular damage with fibrinoid necrosis and perivascular edema.…”