Immunosuppression withdrawal in renal transplantation

Kasiske, Bertram L.; Chakkera, Harini A.; Louis, Thomas A.; Ma, Jun

doi:10.1016/s0041-1345(00)01569-4

Cited by 162 publications

(228 citation statements)

References 4 publications

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“…Similar results were previously reported by Grinyó et al (24), although the risk for acute rejection after Pred withdrawal was 14% in a meta-analysis (22). However, the continuation of CsA and MMF was not used as baseline immunosuppression after Pred withdrawal in most studies included in this meta-analysis.…”

Section: Discussionsupporting

confidence: 89%

Withdrawal of Cyclosporine or Prednisone Six Months after Kidney Transplantation in Patients on Triple Drug Therapy

Gregoor¹,

Sévaux

Ligtenberg

et al. 2002

Journal of the American Society of Nephrology

141

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ABSTRACT. Uncertainty exists regarding the necessity of continuing triple therapy consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx, 212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute rejection occurred in 14 (22%) of 63 patients after CsA withdrawal compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1 (1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic rejection was present in one patient in the control group, in nine patients after CsA withdrawal (P = 0.006 versus control group); and in four patients after discontinuation of Pred (NS). Graft loss occurred in two versus one patient after CsA or Pred withdrawal, respectively, and in two patients in the control group (NS). Patients who successfully withdrew CsA had a significantly lower serum creatinine during follow-up. Pred withdrawal resulted in a reduction in mean arterial pressure, and the total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal at 6 mo after RTx results in a significantly increased incidence of biopsy-proven acute and chronic rejection. Pred withdrawal was safe and resulted in a reduction in mean arterial pressure. However, patient and graft survival and renal function 2 yr after RTx were not different among groups.

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Section: Discussionsupporting

confidence: 89%

Withdrawal of Cyclosporine or Prednisone Six Months after Kidney Transplantation in Patients on Triple Drug Therapy

Gregoor¹,

Sévaux

Ligtenberg

et al. 2002

Journal of the American Society of Nephrology

141

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“…Thus, CsA minimization or withdrawal has been evaluated by numerous authors. A metaanalysis of the studies that investigated CsA discontinuation under azathioprine (AZA) and prednisone (P) reported a higher rate of acute rejection (AR) but no deleterious effect on graft survival (1), although the trials were relatively heterogeneous. The increased risk for AR has been the main limiting factor to CsA withdrawal under AZA and P after kidney transplantation.…”

mentioning

confidence: 99%

Predictive Factors of Acute Rejection after Early Cyclosporine Withdrawal in Renal Transplant Recipients Who Receive Mycophenolate Mofetil

Hazzan¹,

Labalette²,

Copin³

et al. 2005

Journal of the American Society of Nephrology

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The aim of this randomized, open-labeled trial was to compare the incidence of acute rejection after an early (3 mo posttransplantation) withdrawal of cyclosporine (CsA) or mycophenolate mofetil (MMF) in renal transplantation. Among 218 eligible recipients, 108 nonsensitized, rejection-free patients who were under a triple drug regimen (CsA-MMF-prednisone) and had received a first kidney from a deceased donor were enrolled. At 3 mo after graft, they were gradually withdrawn from CsA (MMF group, n ‫؍‬ 54) or MMF (CsA group, n ‫؍‬ 54). A graft biopsy and a pharmacokinetic study of CsA and mycophenolic acid were systematically performed before the randomization. At 1 yr, graft and patient survival rates were 100% in each group. Renal function was improved in the MMF group compared with the CsA group (Cockcroft calculated clearance 64.7 ؎ 18.7 versus 56.5 ؎ 18.0 ml/min; P ‫؍‬ 0.023). However, the probability of acute rejection was higher in the MMF group (18.5 versus 5.6%; P ‫؍‬ 0.045). The 10 patients who developed acute rejection after CsA withdrawal had a significantly higher incidence of borderline changes on the randomization biopsy than the 44 rejection-free patients (five of 10 versus eight of 44; P ‫؍‬ 0.034), and they displayed a lower area under the curve of mycophenolic acid (43 ؎ 9 versus 58 ؎ 22 mg/h per L; P ‫؍‬ 0.045). Multivariate analysis confirmed that borderline changes and area under the curve of mycophenolic acid were significant risk factors of acute rejection after CsA discontinuation. It is concluded that a systematic graft biopsy and a pharmacokinetic study of mycophenolic acid are needed to reduce the risk for acute rejection after CsA withdrawal.

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“…Besides conversion to TRL, complete cessation of CsA is another possibility that has been studied. The results of the meta-analysis by Kasiske et al demonstrate that discontinuation of CsA results in an 11% higher risk for the development of acute rejection than in controls, in kidney transplantation [29]. However, the relative risk of graft failure was not significantly different from that of the control group.…”

Section: Discussionmentioning

confidence: 97%

The relative importance of cyclosporine exposure in heart, kidney or liver transplant recipients on maintenance therapy

et al. 2004

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We investigated the relationship between cyclosporine exposure and the presence of cyclosporine-related side effects and assessed the advantage of the cyclosporine concentration 2 h postdose (C,) over pre-dose concentration (C,) monitoring. Cyclosporine area-under-the-concentration-time curves were measured during the absorption phase (AUCw h) in 49 liver, 28 heart and 26 kidney transplant recipients (time since transplantation > 6 years) with or without cyclosporine-related side effects on maintenance therapy. The cyclosporine Co correlated well with AUCW (r = 0.77), whereas C2 levels correlated strongly with AUCw (r = 0.92). Although we observed a trend towards higher CsA concentrations in transplant recipients with side effects than in patients without CsA toxicity, the large majority of those differences were not statistically significant. Thus, as cyclosporine exposure was not clearly related to the presence of side effects, and CO correlated fairly with AUCM, the advantage of monitoring cyclosporine treatment using C2 rather than Co, may be limited for patients on cyclosporine maintenance therapy.

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Immunosuppression withdrawal in renal transplantation

Cited by 162 publications

References 4 publications

Withdrawal of Cyclosporine or Prednisone Six Months after Kidney Transplantation in Patients on Triple Drug Therapy

Withdrawal of Cyclosporine or Prednisone Six Months after Kidney Transplantation in Patients on Triple Drug Therapy

Predictive Factors of Acute Rejection after Early Cyclosporine Withdrawal in Renal Transplant Recipients Who Receive Mycophenolate Mofetil

The relative importance of cyclosporine exposure in heart, kidney or liver transplant recipients on maintenance therapy

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