Several studies have shown that administering a soluble form of CR1 or Crry can reduce renal injury125,126 and such proteins have an extended half-life when fused to an Ig Fc domain.127 More recently, strategies have been developed to target the recombinant protein to sites

of injury. He et al. targeted recombinant regulatory proteins to the kidney using an Ag-specific single chain Ab fragment.128 In other efforts, the inhibitors were directed to sites of complement activation with the design of a find more fusion protein consisting the C3d-binding domain of CR2 and a regulatory protein partner, either Crry (CR2-Crry) or the SCR1-5 region of fH (CR2-fH).129 In one study of MRL/lpr mice, which are prone to autoimmune glomerulonephritis and vasculitis, CR2-Crry ameliorated disease symptoms compared with untreated mice.130 Studies with these

recombinant proteins have also been performed for other diseases with a strong AP component, including intestinal selleck chemical IRI and collagen-induced arthritis.129,131 These studies demonstrated protection from disease when the complement-targeted fusion proteins were administered, making them excellent candidates to test in additional renal disease models. It is clear that the complement system plays a detrimental role in many kidney diseases and identification and validation of complement inhibitors may provide a promising avenue of drug development for these disorders, which mostly lack effective therapies. The majority of these conditions appear to be mediated by an overactive AP complement

system, which can result from mutations in membrane or fluid-phase complement regulators leading to inadequate control of activation or from gain of function mutations in fB or C3 giving rise to a more stable C3bBb enzyme complex. Although some of these diseases are rare in the population, their studies have provided important insight to the pathogenesis of complement-mediated tissue injury as well as new understanding of mechanisms of action of complement regulatory proteins. These advances have also fueled many efforts to develop targeted therapies for these disorders and it is likely that one or more complement-based drugs for kidney diseases ID-8 will reach the clinic in the near future. Given the fact that complement-mediated kidney pathologies share characteristics with other common diseases such as AMD and rheumatoid arthritis that have been linked to complement and for which intense effort of drug development is also being made, continued translational studies in this field may benefit other areas of investigation of complement biology and therapeutics and vice versa. “
“The aim of the present study was to assess the trajectories of glomerular filtration rate (GFR) and determinants of change during a 3-year period in free-living mixed-ancestry South Africans. In all 320 (78.1% women) adults, aged 56.2 years, from Cape Town were examined in 2008 and 2011.