%0 Journal Article
%T Is There a Role for Mammalian Target of Rapamycin Inhibition in Renal Failure due to Mesangioproliferative Nephrotic Syndrome?
%A Hern¨¢n Trimarchi
%A Mariano Forrester
%A Fernando Lombi
%A Vanesa Pomeranz
%A Romina Iriarte
%A Mar¨ªa Soledad Ra£¿a
%A Pablo Young
%J International Journal of Nephrology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/427060
%X Primary glomerulonephritis stands as the third most important cause of end-stage renal disease, suggesting that appropriate treatment may not be as effective as intended to be. Moreover, proteinuria, the hallmark of glomerular damage and a prognostic marker of renal damage progression, is frequently resistant to thorough control. In addition, proteinuria may be the common end pathway in which different pathogenetic mechanisms may converge. This explains why immunosuppressive and nonimmunosuppressive approaches are partly not sufficient to halt disease progression. One of the commonest causes of primary glomerulonephritis is mesangioproliferative glomerulonephritis. Among the triggered intracellular pathways involved in mesangial cell proliferation, the mammalian target of rapamycin (mTOR) plays a critical role in cell growth, in turn regulated by many cytokines, disbalanced by the altered glomerulopathy itself. However, when inhibition of mTOR was studied in rodents and in humans with primary glomerulonephritis the results were contradictory. In light of these controversial data, we propose an explanation for these results, to dilucidate under which circumstances mTOR inhibition should be considered to treat glomerular proteinuria and finally to propose mTOR inhibitors to be prospectively assessed in clinical trials in patients with primary mesangioproliferative glomerulonephritis, for which a satisfactory standard immunosuppressive regimen is still pending. 1. Introduction The universal and growing impact of chronic diseases is undoubtedly high. While there has been little attention paid to kidney disease on a public health level, the reality is that many countries hardly bear the costs of providing end-stage renal disease care through renal replacement therapy. According to the latest USRDS report, while the prevalence of diabetes has clearly increased and the prevalence of congestive heart failure has remained stable, the prevalence of chronic kidney disease appears to have declined slightly in 2009, from 15.8 percent to 15.1 percent when calculated with the MDRD-4 formula and from 14.7 percent to 14.5 percent when calculated with the CKD-EPI formula; prevalence estimates of chronic kidney disease in USA in 1988¨C1994 had been 12.8 and 12 percent, respectively [1]. Obviously, differences in the prevalence estimates may in part differ depending on the criteria and equations employed. Among the most frequent causes of end-stage renal disease, glomerulonephritis ranks third worldwide. Mesangioproliferative glomerulonephritis, mostly IgA nephropathy, is
%U http://www.hindawi.com/journals/ijn/2012/427060/