Mycophenolate mofetil reduces deterioration of renal function in patients with chronic allograft nephropathy

Given the potency of modern immunosuppressive agents, kidney transplantation across alloantingen barriers is a routine phenomenon with excellent 1-year graft survival in most centers. However, the improvement in 1-year graft survival has not been matched by improvements in long-term graft function and chronic allograft nephropathy (CAN) remains the second commonest cause of graft attrition over time. Calcineurin inhibitors, namely cyclosporine A (CyA) and tacrolimus, have been implicated as causal agents in the development of the fibrotic processes that are the hallmarks of CAN. Many studies have, therefore, concentrated on the improvement of long term graft function through the modulation of immunosuppressive therapy. It is the purpose of this review to describe and appraise the available evidence for the prevention and management of CAN through modulation of immunosuppressive agents.

Section: Mmfmentioning

confidence: 75%

Section: Mmfmentioning

confidence: 95%

Section: Mmfmentioning

confidence: 99%

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What we CAN do about chronic allograft nephropathy: Role of immunosuppressive modulations

Afzali

Taylor

Goldsmith

2005

“…It has been suggested that this improvement is related to the superior immunosuppressive activity of these drugs that allow a reduction in the incidence of not only acute rejection [11,12], but also subclinical rejection [13,14]. Furthermore, it has been suggested that both treatments may decrease the rate of progression of chronic allograft nephropathy (CAN) [13,15,16]. This tendency for a better preservation of renal function became more evident after the introduction of sirolimus.…”

Section: Immunosuppressive Treatment and Renal Functionmentioning

confidence: 97%

Risk factors associated with the deterioration of renal function after kidney transplantation

Serón

Fulladosa

Moreso

2005

Renal function early after transplantation is associated with a large number of risk factors, including donor age and acute rejection. During the 1990s, donor age increased and the incidence of acute rejection decreased. Renal function between the third and sixth month improved slightly, while renal function deterioration between the third or sixth month and the 12th month improved significantly. This modification coincides with the introduction of mycophenolate mofetil and tacrolimus. The tendency for sustained renal improvement early after transplantation became more evident after the introduction of anti-calcineurin-free regimens. Studies of protocol biopsies have shown that there is an increase of glomerular volume after transplantation and that a larger glomerular volume at 4 months is associated with a better glomerular filtration rate. This adaptation mechanism is impaired in patients with chronic allograft nephropathy or in patients with high cyclosporin levels. Taken together, these data suggest that the steady improvement of renal allograft function may be partly explained by a better glomerular adaptation after transplantation because of the avoidance of the vasoconstrictive effect of anti-calcineurinic agents, and a significant decrease in the prevalence of chronic allograft nephropathy early after transplantation.

“…The Spanish Cooperative Study Group of Chronic Allograft Nephropathy prospectively explored the potential therapeutic role of MMF in patients diagnosed with CAN [22]. One hundred-twenty patients with biopsyproven CAN on double or triple therapy with CsA were treated with MMF.…”

Section: Mycophenolate Mofetilmentioning

confidence: 99%

Immunosuppressive treatment and progression of histologic lesions in kidney allografts

Morales

2005

Renal transplantation is the best therapeutic option for patients with end-stage renal disease. Although short-term results are excellent, long-term graft survival has not improved substantially in recent times. Chronic allograft nephropathy (CAN) and death with a functioning graft are the most important causes of graft loss. Recent evidence shows that nephrotoxicity of calcineurin inhibitors contributes to CAN, and the introduction of non-nephrotoxic drugs such as mycophenolate mofetil (MMF) and mammalian target of rapamycin inhibitors may provide new immunosuppressive strategies to improve long-term results after renal transplantation. MMF decreases the risk of developing chronic allograft failure and is useful for treating established CAN, because it has a beneficial effect on allograft fibrosis. Treatment with sirolimus (SRL), a basic immunosuppressive drug given in association with MMF, may offer better renal function, decrease the prevalence of CAN, and downregulate expression of genes responsible for the progression of CAN than treatment with cyclosporine A (CsA). SRL also permits an early elimination of CsA from SRL-CsA-steroid regimens and shows better renal function and improved renal histology without risk of rejection. Notably, this approach improves graft survival at 4 years. Further multicenter studies are needed to determine whether both approaches produce similar results by comparing immunosuppression caused by SRL-based and tacrolimus (TAC)-based treatments. Because TAC is the most commonly used anticalcineurin drug, it is important to compare the effects of steroid-TAC-SRL treatment with and without elimination of TAC. Finally, although caution is needed, the use of non-nephrotoxic immunosuppressive treatment may change the natural history of CAN.