Randomised controlled trial of steroid withdrawal in renal transplant recipients receiving triple immunosuppression

Ratcliffe, Peter J.; Dudley, Chris; Higgins, Robert; Firth, John D.; Smith, B.; Morris, Peter J.

doi:10.1016/s0140-6736(96)02510-x

Cited by 171 publications

(81 citation statements)

References 18 publications

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“…As minimizing immunosuppression is presumed to be beneficial, clinical trials were performed using conversion studies from CsA to AZA or MMF, avoiding or tapering one of the immunosuppressive drugs [6][7][8][9][10]12,13,30].…”

Section: Discussionmentioning

confidence: 99%

Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation

Besouw¹,

Mast²,

Kuiper³

et al. 2002

Clinical and Experimental Immunology

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SUMMARY Stable cadaveric renal transplant patients were routinely converted from cyclosporin A (CsA) to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation to reduce the side effects of long-term immunosuppressive therapy. Thereafter, the AZA and MMF dose was gradually tapered to 50% at 2 years after transplantation. We questioned whether a reduction of immunosuppressive treatment results in a rise of donor-specific T-cell reactivity. Before transplantation (no immunosuppression), 1 year (high dose immunosuppression) and 2 years (low dose immunosuppression) after transplantation, the T-cell reactivity of peripheral blood mononuclear cells (PBMC) against donor and third-party spleen cells was tested in mixed lymphocyte cultures (MLC) and against tetanus toxoid (TET) to test the general immune response. We also measured the frequency of donor and third-party reactive helper (HTLpf) and cytotoxic (CTLpf) T-lymphocyte precursors in a limiting dilution assay. Donor-specific responses, calculated by relative responses (RR = donor/third-party reactivity), were determined. Comparing responses after transplantation during high dose immunosuppression with responses before transplantation (no immmunosuppression), the donor-specific MLC-RR (P = 0·04), HTLp-RR (P = 0·04) and CTLp-RR (P = 0·09) decreased, while the TET-reactivity did not change. Comparing the responses during low dose with high dose immunosuppression, no donor- specific differences were found in the MLC-RR, HTLp-RR and CTLp-RR, although TET-reactivity increased considerably (P = 0·0005). We observed a reduction in donor-specific T-cell reactivity in stable patients after renal transplantation during in vivo high dose immunosuppression. Tapering of the immunosuppressive load had no rebound effect on the donor-specific reactivity, while it allowed recovery of the response to nominal antigens.

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Section: Discussionmentioning

confidence: 99%

Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation

Besouw¹,

Mast²,

Kuiper³

et al. 2002

Clinical and Experimental Immunology

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“…In order to minimize their well-described side effects, there have been a number of attempts to reduce the dosage of corticosteroids, particularly after the advent of cyclosporine, when further reduction in the maintenance dosage was possible. Several trials have been undertaken to evaluate the outcome of corticosteroid withdrawal in patients receiving cyclosporine-based immunosuppression, with, in the end, not completely satisfactory results and an unacceptably high incidence of late rejection (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Most renal transplant patients still receive maintenance corticosteroids chronically.…”

Section: O+-~--r-~~--~-r~--c-~--cmentioning

confidence: 99%

Outcome After Steroid Withdrawal in Pediatric Renal Transplant Patients Receiving Tacrolimus-Based Immunosuppression.

Chakrabarti¹,

Wong²,

Scantlebury³

et al. 1999

Transplantation

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Background. Corticosteroids have always been an integral part of immunosuppressive regimens in renal transplantation. The primary goal of this analysis was to assess the safety of steroid withdrawal in our pediatric renal transplant recipients receiving tacrolimusbased immunosuppression.Methods. Between December 1989 and December 1996, 82 renal transplantations were performed in pediatric patients receiving tacrolimus-based immunosuppression. Two of these patients lost their grafts within 3 weeks of transplantation (and were still on steroids at the. time of graft loss), and were excluded from further analysis. Seventy-four patients (92.5%) were taken off prednisone a median of 5.7 months after transplantation. Of these 74, 56 (70%) remained off prednisone (OFF), and 18 (22.5%) were restarted on prednisone a median of 14.8 months after discontinuing steroids (OFF ~ ON). 6(7.5%) were never taken-off prednisone (ON). The mean follow-up was 59±23 months.Results. The 1-,3-, and 5-year actuarial patient survival rates in the OFF group were 100%, 98%, and 96%,

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“…have made withdrawal controversial. [11][12][13][14] In addition, the results of the Canadian multicenter trial showed a significantly These results suggest that 5 mg/d of prednisone is not a ''physiological'' dose of prednisone. The intracellular effect of decreased 5-year renal allograft survival in patients undergoing steroid withdrawal.…”

Section: Aid Hepa 0006mentioning

confidence: 99%

Prednisone withdrawal late after adult liver transplantation reduces diabetes, hypertension, and hypercholesterolemia without causing graft loss

et al. 1997

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plantation are due to cardiovascular disease and another 40% We prospectively withdrew prednisone in 28 adult paare due to infection. 4 tients who had stable graft function more than 2 yearsWe previously have observed a high prevalence of cardioafter orthotopic liver transplantation (OLTx) and had vascular risk factors in patients late after liver transplantabeen on 5 mg/d prednisone for at least 6 months. Prednition. 4 One year after successful liver transplantation in our sone was decreased from 5 mg/d to 2.5 mg/d for 1 month patient population, the incidence of diabetes was 13% and then stopped completely. Cyclosporine monotherapy the incidence of hypertension was 69.1%. In addition, 31% of was maintained at a level of approximately 200 ng/mL our patients had serum cholesterol levels ú 240 ng/mL at 1 (TDX). Nineteen patients had prednisone withdrawn year. Tapering of prednisone from 10 mg/d to 5 mg/d dewithout complications. Four (14.2%) had modest elevacreased these metabolic complications in some patients and tions in liver function tests (two biopsy proven mild resignificantly decreased serum cholesterol levels. jections and two were not biopsied). These four wereIn this study, we further explore the role of prednisone in treated with methylprednisolone boluses and then withthe development of metabolic complications after liver transdrawal of steroids again. Prednisone was restarted in plantation. We prospectively withdrew prednisone in liver five patients because of generalized fatigue and body transplantation recipients who had survived at least 2 years aches (n Å 4) and colitis (n Å 1). Steroids later were after transplantation to determine if the metabolic complicasuccessfully withdrawn in two of these patients. After tions such as diabetes, hypertension, and hypercholesterolprednisone withdrawal, three of five insulin-dependent emia could be decreased. diabetic patients were able to discontinue insulin therapy and their glycosylated hemoglobin levels improved. ied. In this group during the study period, no diabetic also were excluded because they do not receive maintenance prednibecame normoglycemic, no patient decreased their anti-sone immunosuppression at our center. No children were included hypertensive medicine, and the mean serum cholesterol in this study. levels did not change significantly. We conclude that At the time of the study, 52 patients at our institution were at prednisone withdrawal using cyclosporine monother-least 2 years after OLTx and on 5 mg/d of prednisone. Twelve patients were excluded from this initial study because they had a hisapy late after liver transplantation does not lead to graft Two patients refused participation. Finally, 28 patients were included in the study. No patient was dropped from the study after enrollment. The 24 patients not included in the steroid withdrawal As more patients enjoy long-term survival after liver trans-study were maintained on 5 mg/d prednisone throughout the study period and continued to be followed with monthly laboratory values. planta...

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Randomised controlled trial of steroid withdrawal in renal transplant recipients receiving triple immunosuppression

Cited by 171 publications

References 18 publications

Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation

Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation

Outcome After Steroid Withdrawal in Pediatric Renal Transplant Patients Receiving Tacrolimus-Based Immunosuppression.

Prednisone withdrawal late after adult liver transplantation reduces diabetes, hypertension, and hypercholesterolemia without causing graft loss

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