Is There a Role for Mammalian Target of Rapamycin Inhibition in Renal Failure due to Mesangioproliferative Nephrotic Syndrome?
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...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Nephrology |
| Online Access: | http://dx.doi.org/10.1155/2012/427060 |
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| author | Hernán Trimarchi Mariano Forrester Fernando Lombi Vanesa Pomeranz Romina Iriarte María Soledad Raña Pablo Young |
| author_facet | Hernán Trimarchi Mariano Forrester Fernando Lombi Vanesa Pomeranz Romina Iriarte María Soledad Raña Pablo Young |
| author_sort | Hernán Trimarchi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a3274a5bbfdd4fa9a6bad26ba14cad40 |
| institution | Kabale University |
| issn | 2090-214X 2090-2158 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Nephrology |
| spelling | doaj-art-a3274a5bbfdd4fa9a6bad26ba14cad402025-08-20T03:38:18ZengWileyInternational Journal of Nephrology2090-214X2090-21582012-01-01201210.1155/2012/427060427060Is There a Role for Mammalian Target of Rapamycin Inhibition in Renal Failure due to Mesangioproliferative Nephrotic Syndrome?Hernán Trimarchi0Mariano Forrester1Fernando Lombi2Vanesa Pomeranz3Romina Iriarte4María Soledad Raña5Pablo Young6Division of Nephrology, Department of Medicine, Hospital Británico de Buenos Aires, 1280 Buenos Aires, ArgentinaDivision of Nephrology, Department of Medicine, Hospital Británico de Buenos Aires, 1280 Buenos Aires, ArgentinaDivision of Nephrology, Department of Medicine, Hospital Británico de Buenos Aires, 1280 Buenos Aires, ArgentinaDivision of Nephrology, Department of Medicine, Hospital Británico de Buenos Aires, 1280 Buenos Aires, ArgentinaDivision of Nephrology, Department of Medicine, Hospital Británico de Buenos Aires, 1280 Buenos Aires, ArgentinaDivision of Nephrology, Department of Medicine, Hospital Británico de Buenos Aires, 1280 Buenos Aires, ArgentinaDivision of Nephrology, Department of Medicine, Hospital Británico de Buenos Aires, 1280 Buenos Aires, ArgentinaPrimary 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.http://dx.doi.org/10.1155/2012/427060 |
| spellingShingle | Hernán Trimarchi Mariano Forrester Fernando Lombi Vanesa Pomeranz Romina Iriarte María Soledad Raña Pablo Young Is There a Role for Mammalian Target of Rapamycin Inhibition in Renal Failure due to Mesangioproliferative Nephrotic Syndrome? International Journal of Nephrology |
| title | Is There a Role for Mammalian Target of Rapamycin
Inhibition in Renal Failure due to Mesangioproliferative Nephrotic Syndrome? |
| title_full | Is There a Role for Mammalian Target of Rapamycin
Inhibition in Renal Failure due to Mesangioproliferative Nephrotic Syndrome? |
| title_fullStr | Is There a Role for Mammalian Target of Rapamycin
Inhibition in Renal Failure due to Mesangioproliferative Nephrotic Syndrome? |
| title_full_unstemmed | Is There a Role for Mammalian Target of Rapamycin
Inhibition in Renal Failure due to Mesangioproliferative Nephrotic Syndrome? |
| title_short | Is There a Role for Mammalian Target of Rapamycin
Inhibition in Renal Failure due to Mesangioproliferative Nephrotic Syndrome? |
| title_sort | is there a role for mammalian target of rapamycin inhibition in renal failure due to mesangioproliferative nephrotic syndrome |
| url | http://dx.doi.org/10.1155/2012/427060 |
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