Long‐Term Use of Mycophenolate Mofetil is Associated With a Reduction in the Incidence and Risk of Late Rejection

Meier-Kriesche, Herwig Ulf; Steffen, Bettina J.; Hochberg, Alan M.; Gordon, Robert D.; Liebman, Michael; Morris, Jonathan; Kaplan, Bruce

doi:10.1034/j.1600-6143.2003.30112.x

Cited by 118 publications

(61 citation statements)

References 15 publications

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“…A similar effect has been seen in the 5-yr analysis of a recent clinical trial of cyclosporin A versus tacrolimus: the patients with more early rejection showed more late loss of GFR (16). Thus, one reason for the improved late stability of GFR is probably superior control of late rejection by the new immunosuppressive therapies (17). Late loss of CrCl after early rejection could reflect late recurrent or smoldering rejection after early rejection, possibly as a result of subclinical rejection (18,19).…”

Section: Discussionsupporting

confidence: 50%

The Stability of the Glomerular Filtration Rate after Renal Transplantation Is Improving

Gourishankar¹,

Hunsicker

Jhangri

et al. 2003

Journal of the American Society of Nephrology

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Abstract. The 6-mo function and the stability of function posttransplantation in 429 cadaver renal transplants was investigated from 1990 to 2000. The 6-mo creatinine clearance (CrCl) and the rate of change of CrCl beyond 6 mo posttransplantation were calculated. The mean 6-mo CrCl was 64.6 Ϯ 1.1 ml/min and was stable between 1990 and 2000. The net slope of CrCl was Ϫ1.4 Ϯ 0.5 ml/min per yr. The slope has improved in recent years, such that the mean slopes in the period after 1997 are actually positive (ϩ3.5 ml/min per yr). The slope of CrCl beyond 6 mo was not related to the actual value of the 6 mo CrCl, i.e., there was no accelerated loss of function at low CrCl levels. The 6-mo CrCl was independently determined by donor factors (age, gender), recipient factors (age, gender), and immune factors (rejection episodes, regraft status). The slope of the CrCl correlated independently with the transplant year, recipient gender, rejection episodes, diastolic BP, and the choice of immunosuppressive drugs. Cytomegalovirus infection and mismatch status and lipid levels and treatment were not independently associated with slope or 6-mo CrCl. Thus, the most striking change in the course of renal transplants over the past decade is the new stability of function, correlating with reduced rejection and probably due at least in part to the new immunosuppressive agents. Despite continued calcineurin inhibitor use, late improvement in function now occurs in many cadaver kidney transplants, suggesting a previously unappreciated capacity for functional adaptation.With improved control of early rejection and graft loss (1), the emphasis in renal transplantation has now shifted to improving the long-term transplant course. This includes a focus on reducing late graft loss by stabilizing and improving renal function, controlling immunosuppressive side effects, and reducing risk factors for patient survival. The frequency of late graft loss remains excessive: approximately 7% of renal transplants currently functioning in Canada and the United States will fail each year, with approximately half of the losses being due to patient death and the remainder being due to loss of function. In studying the failures that are due to loss of renal function, transplant population studies have usually examined outcomes such as graft survival and half-life. However, these approaches are limited because they give information only about grafts that have failed completely and do not distinguish grafts with poor function from the outset from grafts with excellent function that subsequently deteriorate.Additional information can be gained by looking at renal function outcomes and change in function, permitting examination of the whole population, not just failures. Renal function has long been recognized as a critical determinant of the probability of graft survival (2), and its critical role as a predictor of survival has recently been confirmed in the United Network for Organ Sharing (UNOS) database (3). Serum creatinine and calculated and measured cr...

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Section: Discussionsupporting

confidence: 50%

The Stability of the Glomerular Filtration Rate after Renal Transplantation Is Improving

Gourishankar¹,

Hunsicker

Jhangri

et al. 2003

Journal of the American Society of Nephrology

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“…In this study, the decrease in the incidence of acute rejection partly account for this result, since rejection-free patients had also benefited from the MMF therapy [17]. Recently, the demonstration that MMF protects against the long-term deterioration of renal allograft function has suggested that this drug has a beneficial impact on chronic allograft nephropathy [18]. Two others studies support these results and show a significant reduction in late acute rejection risk [19] and long-term graft loss with MMF 1201.…”

Section: Discussionmentioning

confidence: 67%

“…On the other hand, maintenance therapy with MMF for a longer period could be required, as previously mentioned, to improve the long-term results [18,19,201. However, maintenance with MMF, with a 50% CsA reduction after the first year post-transplantation, could be an alternative cost-effective strategy [26].…”

Section: Discussionmentioning

confidence: 99%

Improvement in long-term graft survival in cadaveric renal transplant recipients treated with mycophenolate mofetil

Hazzan¹,

François²,

Guilhot³

et al. 2004

Transpl Int

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Though mycophenolate mofetil has markedly reduced the incidence of acute rejection in renal transplantation, a significant improvement in graft survival has been more difficult to demonstrate. This retrospective study compares an historical control group of 210 consecutive renal transplant patients, who had received ATG induction associated with cyclosporin, prednisolone and azathioprine, with 187 patients receiving mycophenolate instead of azathioprine. The incidence of acute rejection was decreased with mycophenolate. In rejection-free patients, the 3-year graft survival rates were equivalent. In contrast, graft survival at 3 years improved significantly for patients who experienced a rejection crisis and remained under the initial triple drug regimen with mycophenolate compared to the patients of the historical group who were kept on azathioprine after a rejection episode. In conclusion, mycophenolate mofetil is not only able to reduce the incidence of acute rejection but could also improve the prognostic significance of acute rejection crises.

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“…In combination with a CNI, MMF is associated with a decreased relative risk of graft failure independent of its effects on acute rejection as opposed to AZA (17). MMF also provides significant protection against long-term deterioration of renal allograft function and prophylaxis against late rejection ]mt]1 yr after transplantation (16,18). Notably, leucopenia, anemia, and gastrointestinal side effects are common with MMF (19).…”

Section: Rationale Underlying Steroid and Cni Withdrawal/ Avoidance Rmentioning

confidence: 99%

“…MMF, an antiproliferative agent when used with CNI and corticosteroids, affords excellent protection from acute rejection with no accompanying intrinsic nephrotoxicity (15,16). In combination with a CNI, MMF is associated with a decreased relative risk of graft failure independent of its effects on acute rejection as opposed to AZA (17).…”

Section: Rationale Underlying Steroid and Cni Withdrawal/ Avoidance Rmentioning

confidence: 99%

Minimizing Immunosuppression, an Alternative Approach to Reducing Side Effects

Srinivas¹,

Meier‐Kriesche²

2008

Clinical Journal of the American Society of Nephrology

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122

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Exceptionally low acute rejection rates and excellent graft survival can be achieved with cyclosporine and tacrolimus (CNI)-based immunosuppressive protocols that incorporate antiproliferative immunosuppressants and corticosteroids. However, despite short-term success, long-term attrition of graft function and side effects of immunosuppressive agents continue to be significant problems, leaving clinicians looking for possible interventions. CNI nephrotoxicity is but one of numerous factors that may contribute to long-term damage in transplant kidneys. Metabolic, cosmetic, and neuropsychiatric complications of steroids affect quality of life after transplantation. Newer immunosuppressive agents such as mycophenolate mofetil and sirolimus (Rapa) have raised the possibility of withdrawing or avoiding CNIs or steroids altogether. In this report we review studies that address either CNI or steroid minimization strategies and discuss their risks versus benefits. Given the accumulated experience to date, in our opinion the use of CNIs and steroids as part of immunosuppressive regimens remains the proven standard of care for renal transplant patients. The long-term safety and efficacy of CNI and steroid minimization strategies needs to be further validated in controlled clinical trials with adequate long-term follow-up.

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Long‐Term Use of Mycophenolate Mofetil is Associated With a Reduction in the Incidence and Risk of Late Rejection

Cited by 118 publications

References 15 publications

The Stability of the Glomerular Filtration Rate after Renal Transplantation Is Improving

The Stability of the Glomerular Filtration Rate after Renal Transplantation Is Improving

Improvement in long-term graft survival in cadaveric renal transplant recipients treated with mycophenolate mofetil

Minimizing Immunosuppression, an Alternative Approach to Reducing Side Effects

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