title: The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathy.
abstract: 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.
authors.affiliation: Division of Nephrology, Department of Medicine, Division of Cardiovascular Surgery, University of Maryland Medical Systems, mweir@medicine.umaryland.edu, Department of Surgery, University of Maryland Medical Systems, 22 S. Greene Street, Room N3W143, Baltimore, MD 21201, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Weir
authors.affiliation: Division of Nephrology, Department of Medicine, Division of Cardiovascular Surgery, University of Maryland Medical Systems, Department of Surgery, University of Maryland Medical Systems, 22 S. Greene Street, Room N3W143, Baltimore, MD 21201, USA.
authors.lastname: Chiming Wei
keywords: angiotensin II; chronic allograft nephropathy; transforming growth factor-beta