The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathy
Chronic allograft nephropathy is the most prevalent cause of graft dysfunction and failure. Its pathogenesis and treatment remains poorly defined. The calcineurin inhibitors, cyclosporine and tacrolimus, may play a role in the progressive loss of renal function in patients with chronic allograft nep...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publications
2001-03-01
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| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.1177/14703203010020013201 |
| _version_ | 1797285466476642304 |
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| author | Matthew R Weir Chiming Wei |
| author_facet | Matthew R Weir Chiming Wei |
| author_sort | Matthew R Weir |
| collection | DOAJ |
| description | Chronic allograft nephropathy is the most prevalent cause of graft dysfunction and failure. Its pathogenesis and treatment remains poorly defined. The calcineurin inhibitors, cyclosporine and tacrolimus, may play a role in the progressive loss of renal function in patients with chronic allograft nephropathy. This effect may be either related to the direct stimulation of profibrogenic cytokines such as transforming growth factor (TGF-β) or indirect mechanisms, through increases in blood pressure or alterations in either carbohydrate or lipid metabolism. Experimental studies have demonstrated that angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) can attenuate cyclosporine-mediated increases in TGF-β production in renal tissue. Clinical studies have demonstrated that either cyclosporine or tacrolimus dose reduction may help reduce the rate of loss of renal function in patients with chronic allograft nephropathy. Moreover, other studies have demonstrated that a chronic reduction in the dose of cyclosporine in transplant patients can reduce serum TGF-β levels. Treatment with an ARB can normalise the plasma levels of TGF-β in renal transplant patients receiving cyclosporine. All these observations suggest that there may be a role of cyclosporine, and possibly tacrolimus, in worsening chronic allograft nephropathy through their effects on the renin-angiotensin-aldosterone system (RAAS) and TGF-β production. |
| first_indexed | 2024-03-07T18:03:34Z |
| format | Article |
| id | doaj.art-5ee78d6693ac406ba6ff75deb54b9d6c |
| institution | Directory Open Access Journal |
| issn | 1470-3203 1752-8976 |
| language | English |
| last_indexed | 2024-03-07T18:03:34Z |
| publishDate | 2001-03-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-5ee78d6693ac406ba6ff75deb54b9d6c2024-03-02T10:10:44ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32031752-89762001-03-01210.1177/1470320301002001320110.1177_14703203010020013201The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathyMatthew R Weir Chiming WeiChronic allograft nephropathy is the most prevalent cause of graft dysfunction and failure. Its pathogenesis and treatment remains poorly defined. The calcineurin inhibitors, cyclosporine and tacrolimus, may play a role in the progressive loss of renal function in patients with chronic allograft nephropathy. This effect may be either related to the direct stimulation of profibrogenic cytokines such as transforming growth factor (TGF-β) or indirect mechanisms, through increases in blood pressure or alterations in either carbohydrate or lipid metabolism. Experimental studies have demonstrated that angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) can attenuate cyclosporine-mediated increases in TGF-β production in renal tissue. Clinical studies have demonstrated that either cyclosporine or tacrolimus dose reduction may help reduce the rate of loss of renal function in patients with chronic allograft nephropathy. Moreover, other studies have demonstrated that a chronic reduction in the dose of cyclosporine in transplant patients can reduce serum TGF-β levels. Treatment with an ARB can normalise the plasma levels of TGF-β in renal transplant patients receiving cyclosporine. All these observations suggest that there may be a role of cyclosporine, and possibly tacrolimus, in worsening chronic allograft nephropathy through their effects on the renin-angiotensin-aldosterone system (RAAS) and TGF-β production.https://doi.org/10.1177/14703203010020013201 |
| spellingShingle | Matthew R Weir Chiming Wei The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathy Journal of the Renin-Angiotensin-Aldosterone System |
| title | The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathy |
| title_full | The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathy |
| title_fullStr | The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathy |
| title_full_unstemmed | The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathy |
| title_short | The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathy |
| title_sort | role of angiotensin ii and tgf beta on the progression of chronic allograft nephropathy |
| url | https://doi.org/10.1177/14703203010020013201 |
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