Who Should Be Converted From Cyclosporine to Conventional Immunosuppression in Kidney Transplantation, and Why

Versluis, Dennis; Wenting, G J; Derkx, F. H. M.; Schalekamp, M. A. D. H.; Jeekel, J.; Weimar, Willem

doi:10.1097/00007890-198709000-00012

Cited by 58 publications

(15 citation statements)

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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%

“…nephrotoxicity and hypertension [2,4,5]. To minimize these side effects, and in an attempt to preserve benefits on graft survival, administration of CsA for one year and thereafter, conversion to the less nephrotoxic drugs AZA [6][7][8][9][10] or mycophenolate mofetil (MMF) [10], would be an option. To reduce the long-term side effects (cancer) [11] of immunosuppressive agents, and to improve the quality of life after transplantation, the AZA, MMF or prednison (Pred) dose can be tapered [10,12,13], provided this is not accompanied by rejection.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

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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“…Azathioprine has no known hyperlipidemic effect, and in renal allograft recipients significant decreases in serum triglyceride and cholesterol levels were observed when patients converted from cyclosporine to azathioprine immunosuppression. 32,33 Hypercholesterolemia with a predominant elevation of LDL cholesterol levels is the most frequently cited complication in posttransplant patients. [34][35][36] Cyclosporine and prednisone were found, by multivariate analysis, to be independent factors in the pathogenesis of posttransplant hypercholesterolemia.…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein changes in children after liver transplantation: Mild hypertriglyceridemia and a decrease in HDL/HDL ratio

Granot

1998

Hepatology

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Hyperlipidemia is frequently observed in patients who undergo renal, cardiac, bone marrow, or liver transplantation, and its contribution to the long-term morbidity and survival of patients with organ transplants may be substantial. In the few studies that have focused on the pediatric age group, findings have been inconsistent. The lipoprotein profile of 10 children after liver transplantation was characterized and compared with those in normal population controls and 10 healthy siblings. Hyperlipidemia is frequently observed in patients who undergo renal, cardiac, bone marrow, or liver transplantation. 1-5 Because hyperlipidemia constitutes a predisposing factor to atherosclerosis, its influence on the long-term morbidity and survival of organ transplantation patients could be important. Cyclosporine therapy has been implicated as the major cause of posttransplantation hyperlipidemia, causing not only hypercholesterolemia but also hypertriglyceridemia. Sustained elevations of cholesterol and triglyceride levels have been noted not only posttransplantation, but also in nontransplantation patients receiving cyclosporine. These elevations are noted within 1 to 2 weeks of therapy. 5-7 Although a concomitant decrease in posttransplantation high-density lipoprotein (HDL) cholesterol levels has also been attributed to cyclosporine, 8 in a group of psoriasis patients treated with cyclosporine no consistent changes in HDL cholesterol levels were noted. 6 In contrast to these observations, which attribute the hyperlipidemia mainly to cyclosporine, a recent study in renal transplantation patients noted similar elevations of plasma lipids in patients undergoing either triple therapy with cyclosporine, prednisone, and azathioprine or solely prednisone and azathioprine. 9 Indeed, this was further substantiated in heart transplantation patients in whom total cholesterol levels were significantly higher only in the group of patients requiring corticosteroid maintenance immunosuppression. 10 In adults, posttransplantation hyperlipidemia is probably multifactorial with obesity, renal and liver dysfunction, diabetes mellitus, drug therapy, and a genetic predisposition playing a role. [11][12][13][14][15][16] In posttransplantation children who are otherwise healthy, with normal liver and renal function, these factors do not apply. Furthermore, familial disorders such as familial combined hyperlipidemia, type V dyslipoproteinemia, and dysbetalipoproteinemia usually do not manifest in childhood and are completely expressed only in adulthood, 17 thus eliminating additional confounding factors. Yet few studies have focused on the pediatric age group. Whereas an increase in total cholesterol and triglyceride levels was found in children who had undergone a renal transplantation, 18 only a moderate hypertriglyceridemia, normal total cholesterol, and a decrease in HDL levels were observed in four of six children after a liver transplantation. 19 McDiarmid et al. 20 conducted a longitudinal cohort study in 102 pediatric liver recipient...

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“…Insulin treatment was no longer needed in 6 of 8 patients 3 months after conversion of immunosuppres sion from CS-A to azathioprine. In another series, oral glucose tolerance testing induced less hyperglycemia 3 months after conversion from CS-A to azathioprine [29,34], although fasting glucose or insulin concentrations did not change. In contrast, glucose tolerance deteriorated, and the insulinogenic index, an indicator of insulin release, decreased when CS-A was introduced for immu nosuppression in renal tansplant patients [43], Ôst et al [44] found normal K values during intravenous glucose tolerance testing in 13 out of 14 renal transplant patients treated with azathioprine and prednisolone.…”

Section: Dr Hörimentioning

confidence: 91%

“…According to recent observations of Verrill et al [31] and Nemunaitis et al [32] CS-A can easily be bound to triglyceride-containing chylomycrons and very low density lipoprotein and consequently would not be bio logically available to either lymphocytes or kidney tissue. On the other hand, Versluis et al [33,34] studied nondia betic recipients of cadaveric renal transplants before and 3 months after conversion from CS-A to azathioprine. In all patients fasting serum triglyceride and cholesterol lev 364 Fcinstein/Wanncr/Böhlcr/Hörl Endocrine and Metabolic Disorders following Kidney Transplantation els decreased.…”

Section: Dr Feinstein Thank You Dr Wanner Dr Hörl Will You Commementioning

confidence: 99%

Endocrine and Metabolic Disorders following Kidney Transplantation

Feinstein

Wanner

Böhler³

et al. 1992

Am J Nephrol

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Who Should Be Converted From Cyclosporine to Conventional Immunosuppression in Kidney Transplantation, and Why

Cited by 58 publications

References 0 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

Lipoprotein changes in children after liver transplantation: Mild hypertriglyceridemia and a decrease in HDL/HDL ratio

Endocrine and Metabolic Disorders following Kidney Transplantation

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