author = {Trimarchi, Hernán. and Duboscq, Cristina.}, title = {{Proteinuria: A Cross Road Where the Complement and the Plasminogen-plasmin Systems Meet}}, journal ={Journal of Integrative Nephrology and Andrology}, volume ={3}, number ={2}, pages = {37-47}, doi = {10.4103/2394-2916.181217}, year = {2016}, abstract ={Proteinuria is the hallmark of nephrotic syndrome and a surrogate of progression of renal disease and a risk factor of cardiovascular morbidity. Once proteinuria occurs secondary to glomerular damage, its reabsorption at the proximal tubule causes a constant interstitial inflammation that will eventually lead to a graduate loss of kidney function due to fibrosis, ischemia and tubular atrophy. The plasminogen-plasmin system plays a local critical role in amplifying podocyte damage, deepening the generation of edema, cross-linking inflammatory components at the interstitium and determining the terminal fibrotic processes. Plasmin activity also causes inflammation through the complement system. The interaction between the complement and the plasminogen-plasmin systems is critical in the progression of interstitial inflammation. Plasmin is capable of cleaving C3 and C5 components of the complement system. Moreover, C3a and C5a fractions are chemoattractants of neutrophils and monocytes. The complement system is also involved in microvascular thrombosis contributing to glomerular sclerosis and interstitial fibrosis through ischemic processes. A regulator of plasmin activity is plasminogen activator inhibitor-1, a leading molecule involved in fibrosis and sclerosis, particularly augmented in glomerulopathies. Unraveling the interactions between the plasminogen-plasmin and complement systems will undoubtedly lead to more specific therapies for glomerular diseases.}, URL ={http://www.journal-ina.com/article.asp?issn=2394-2916;year=2016;volume=3;issue=2;spage=37;epage=47;aulast=Trimarchi;t=6}, eprint ={http://www.journal-ina.com/article.asp?issn=2394-2916;year=2016;volume=3;issue=2;spage=37;epage=47;aulast=Trimarchi;t=6} }