Steroid Withdrawal in Renal Transplant Patients on Triple Therapy with a Calcineurin Inhibitor and Mycophenolate Mofetil: A Meta-analysis of Randomized, Controlled Trials

Pascual, Julio; Quereda, C.; Zamora, Javier; Hernández, Domingo

doi:10.1097/01.tp.0000140969.43761.1f

Cited by 143 publications

(78 citation statements)

References 43 publications

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“…With introduction of new and more powerful maintenance immunosuppressive agents, there were new trials of late prednisone minimization. Again, these trials were generally associated with significantly increased AR rates (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Ten-Year Outcome after Rapid Discontinuation of Prednisone in Adult Primary Kidney Transplantation

Rizzari¹,

Suszynski²,

Gillingham³

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Rapid discontinuation of prednisone after kidney transplantation potentially allows for minimization of steroid-related side effects. Although intermediate-term data with rapid discontinuation of prednisone have been promising, concern still exists regarding long-term outcomes. The 10-year experience is reported herein.Design, setting, participants, & measurements Between October 1, 1999 and December 31, 2010, 1241 adult primary kidney transplants (791 living donor and 450 deceased donor) were performed using a protocol in which prednisone is discontinued after postoperative day 5. The 10-year actuarial recipient and graft survival rates and prednisone-related side effects were studied.Results Ten-year actuarial patient survival was 71% for living donor transplants and 62% for deceased donor transplants; 10-year graft survival was 61% for living donor transplants and 51% for deceased donor transplants, and was comparable to 10-year Scientific Registry of Transplant Recipients national data. Ten-year deathcensored graft survival was 79% for living donor transplants and 80% for deceased donor transplants. Ten-year acute rejection rates were 25% for deceased donor transplants and 31% for living donor transplants; 10-year chronic rejection (interstitial fibrosis/tubular atrophy) rates were 39% for deceased donor transplants and 47% for living donor transplants. For nondiabetic recipients of living donor or deceased donor allografts, the incidence of new-onset diabetes was significantly lower than in historical controls on prednisone (P,0.001). We also found significantly reduced rates of cataracts, avascular necrosis, and cytomegalovirus infection in some subgroups.Conclusions Prednisone-related side effects can be minimized in a protocol incorporating rapid discontinuation of prednisone for maintenance immunosuppression. Ten-year patient and graft outcomes remain acceptable.

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Section: Introductionmentioning

confidence: 99%

Ten-Year Outcome after Rapid Discontinuation of Prednisone in Adult Primary Kidney Transplantation

Rizzari¹,

Suszynski²,

Gillingham³

et al. 2012

Clinical Journal of the American Society of Nephrology

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“…A new evaluation of this topic including only randomised, controlled trials based on currently used, new, potent therapy with CNI and MMF, published by Pascual et al [77], showed that renal allograft recipients on triple therapy are at low but significant risk of acute rejection after steroid withdrawal but do not suffer an increased risk of early graft failure. Opelz et al performed a large prospective study of steroid withdrawal within the framework of the Collaborative Transplant Study to analyse long-term graft and patient outcome in renal and heart transplant recipients.…”

Section: Corticosteroid-sparing Corticosteroid-withdrawal and Steroimentioning

confidence: 98%

Current concepts and perspectives of immunosuppression in organ transplantation

Scherer

Banas

Mantouvalou

et al. 2007

Langenbecks Arch Surg

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We review current trends of immunosuppressive protocols in liver and kidney transplantation, focusing on calcineurin-inhibitor-sparing protocols, mammalian-target-of-rapamycin (mTOR) inhibitor based-protocols and corticosteroid-avoidance protocols, being aware of the fact, that most of these strategies could be applicable for other transplanted organs, too. Finally, we describe future trends and new developments that are rising on the horizon.

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“…5) Even now, steroid withdrawal does not have a satisfactory outcome after renal transplantation. [6][7][8][9][12][13][14] Currently, there are no indicators to predict which patients can withdraw steroid safely. Only one study has investigated steroid withdrawal based on pharmacodynamic methods and suggested that the number of donor-specific cytotoxic T lymphocytes increases in the presence of prednisolone in patients who experience acute rejec- The incident group included patients in whom the S-Cr or BUN levels increased, who experienced steroid withdrawal syndrome, or for whom the steroid dose was increased or steroid administration restarted and non-incident group included patients who did not fall into either of these categories.…”

Section: Discussionmentioning

confidence: 99%

Steroid Withdrawal Based on Lymphocyte Sensitivity to Endogenous Steroid in Renal Transplant Recipients

Takeuchi

Matsuno²,

Hirano

et al. 2011

Biological & Pharmaceutical Bulletin

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Though steroid withdrawal is done in many renal transplant recipients, some patients must restart steroids. Little report has investigated steroid withdrawal under pharmacodynamic monitoring. We assessed lymphocyte sensitivity to endogenous cortisol as a biomarker for determining the safety of steroid withdrawal in renal transplant patients, as we hypothesized that patients hyposensitive to cortisol could not be sufficiently immunosuppressed by their intrinsic cortisol as a substitute for the reduced or withdrawn steroid. Lymphocyte sensitivity to cortisol was examined in 30 long stable renal transplant recipients. Lymphocyte sensitivity to cortisol and its relationship with the clinical outcome after steroid reduction and withdrawal was investigated. The lymphocyte sensitivities to cortisol were estimated as IC 50 of lymphocyte blastogenesis. The lymphocyte proliferation rate for concentration of serum cortisol compared between incident and non-incident groups. Serum creatinine levels (SCr) increased in a significantly higher number of patients hyposensitive to cortisol (IC 50 м м10000 ng/ml) than in normally sensitive patients (IC 50 Ͻ Ͻ10000 ng/ml). The incidences of steroid withdrawal syndrome and necessity for increasing steroid dose or restarting steroid administration were also higher in the patients hyposensitive to cortisol. The patients in whom the lymphocyte proliferation rate was less than 60% did not show increase in S-Cr, experience steroid withdrawal symptoms, or require an increase in the steroid dose or restart of steroid administration. The patients who have the normal IC 50 values of cortisol, can withdraw steroid more safely. The lymphocyte sensitivity to cortisol may be a useful biomarker for selecting patients who can sustain steroid withdrawal.

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Steroid Withdrawal in Renal Transplant Patients on Triple Therapy with a Calcineurin Inhibitor and Mycophenolate Mofetil: A Meta-analysis of Randomized, Controlled Trials

Cited by 143 publications

References 43 publications

Ten-Year Outcome after Rapid Discontinuation of Prednisone in Adult Primary Kidney Transplantation

Ten-Year Outcome after Rapid Discontinuation of Prednisone in Adult Primary Kidney Transplantation

Current concepts and perspectives of immunosuppression in organ transplantation

Steroid Withdrawal Based on Lymphocyte Sensitivity to Endogenous Steroid in Renal Transplant Recipients

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