Hindawi Publishing Corporation International Journal of Nephrology Volume 2012, Article ID 427060, 6 pages doi:10.1155/2012/427060 Review Article Is There a Role for Mammalian Target of Rapamycin Inhibition in Renal Failure due to Mesangioproliferative Nephrotic Syndrome? Hern a´n Trimarchi, Mariano Forrester, Fernando Lombi, Vanesa Pomeranz, Romina Iriarte, Marı´a Soledad Ran˜ a, and Pablo Young Division of Nephrology, Department of Medicine, Hospital Brita´nico de Buenos Aires, 1280 Buenos Aires, Argentina Correspondence should be addressed to Herna´n Trimarchi, htrimarchi@hotmail.com Received 5 January 2012; Revised 16 February 2012; Accepted 22 March 2012 Academic Editor: Claudio Bazzi Copyright © 2012 Herna´n Trimarchi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 1988–1994 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, glomeru- lonephritis ranks third worldwide. Mesangioproliferative glomerulonephritis, mostly IgA nephropathy, is the most frequent primary glomerular disorder worldwide, and progressive mesangioproliferative nephropathy constitutes a major cause of end-stage renal disease [2, 3]. Recent long-term controlled studies assessing the prognosis have shown that the condition does not represent a benign disorder as previously mentioned [4–7]. Once renal function impairment develops, end-stage renal disease appears inevitable, often in the long term. Over 25 years of followup, about 30–50% of patients with IgAN will enter renal replacement therapy [8, 9]. Other causes of mesangial glomerulonephritis consist of pure mesangial