Reduced-dose Cyclosporine with Mycophenolate Mofetil and Prednisone Significantly Improves the Long-term Glomerular Filtration Rate and Graft Survival

Wang, Rending; Xü, Ying; Wu, Jiang; Wang, Yimin; He, Qing; Chen, Jianghua

doi:10.2169/internalmedicine.52.8457

Cited by 2 publications

(2 citation statements)

References 26 publications

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“…SRL) at an early or late phase of the transplant. However, such an approach may result in a greater frequency of late-onset AR events [Wang et al 2013; Burkhalter et al 2012]. Consequently there may be need for a greater amount of steroid rescue treatments, which in turn may promote metabolic disturbances.…”

Section: Role Of Combined (Maintenance) Therapy In Adverse Metabolic mentioning

confidence: 99%

Metabolic consequences of modern immunosuppressive agents in solid organ transplantation

Bamgbola

2016

Therapeutic Advances in Endocrinology

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Among other factors, sophistication of immunosuppressive (IS) regimen accounts for the remarkable success attained in the short- and medium-term solid organ transplant (SOT) survival. The use of steroids, mycophenolate mofetil and calcineurin inhibitors (CNI) have led to annual renal graft survival rates exceeding 90% in the last six decades. On the other hand, attrition rates of the allograft beyond the first year have remained unchanged. In addition, there is a persistent high cardiovascular (CV) mortality rate among transplant recipients with functioning grafts. These shortcomings are in part due to the metabolic effects of steroids, CNI and sirolimus (SRL), all of which are implicated in hypertension, new onset diabetes after transplant (NODAT), and dyslipidemia. In a bid to reduce the required amount of harmful maintenance agents, T-cell-depleting antibodies are increasingly used for induction therapy. The downsides to their use are greater incidence of opportunistic viral infections and malignancy. On the other hand, inadequate immunosuppression causes recurrent rejection episodes and therefore early-onset chronic allograft dysfunction. In addition to the adverse metabolic effects of the steroid rescue needed in these settings, the generated proinflammatory milieu may promote accelerated atherosclerotic disorders, thus setting up a vicious cycle. The recent availability of newer agent, belatacept holds a promise in reducing the incidence of metabolic disorders and hopefully its long-term CV consequences. Although therapeutic drug monitoring as applied to CNI may be helpful, pharmacodynamic tools are needed to promote a customized selection of IS agents that offer the most benefit to an individual without jeopardizing the allograft survival.

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Section: Role Of Combined (Maintenance) Therapy In Adverse Metabolic mentioning

confidence: 99%

Metabolic consequences of modern immunosuppressive agents in solid organ transplantation

Bamgbola

2016

Therapeutic Advances in Endocrinology

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“…Concurrent steroid use may potentiate the metabolic complications [21]. Although lower doses of CNI may minimize adverse effects in high risk patients, there may be need for larger doses of steroids to prevent rejection episodes [22]. On the other hand, steroid use may attenuate CNI toxicity by decreasing its tubular accumulation via the activation of P-glycoprotein, a multi-drug efflux system [23].…”

Section: Combination Therapy With Steroidsmentioning

confidence: 99%

A Critical Review of Steroid Immunotherapy in Kidney Transplantation

Bamgbola¹

2015

Int J Immunol Immunother

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Steroid immunosuppression has maintained a long-lasting relevance in renal transplantation. In addition to its role in preserving allograft survival, it is often the first line agent in the rescue treatment of acute rejection events. Its major drawbacks include metabolic adverse effects and long-term cardiovascular morbidities. Motivated by the need to avoid growth impairment, pediatric renal transplant community provided a template for steroid minimization strategy. Steroid sparing regimens are often successful in the context of induction therapy with lymphocyte depleting agents. Because most randomized controlled trials are conducted for duration of 1 to 5 years, it is unclear if steroid-based protocol confers a longer renal allograft life span. By avoiding earlyonset rejection, steroid prevents exposure of immunogenic epitopes and therefore reduces the development of late-onset antibodymediated allograft injury. In contrast to the calcineurin inhibitors, steroid promotes allograft tolerance by enhancing preservation of the regulatory T cells. It suppresses inflammatory response to ischemic reperfusion events as produced by transplant surgery. Its anti-inflammatory effects are most beneficial in patients with high immunologic risk profiles. Finally, future therapeutic approach may embrace careful selection of most suitable drug regimen for an individual by using bio-molecular resources for risk categorization. analysis of the role of other classes of ISA, readers are referred to previous excellent reviews by other authors [1,2]. Steroids: historical context Steroid was a pioneering ISA for the first cohort of kidney transplant recipients (KTR) in the early 1960s [3]. Its combination with azathioprine (AZA) produced a very modest one-year graft survival rate, barely reaching 40 to 50% [3]. Subsequent introduction of calcineurin inhibitors (CNI), mycophenolate mofetil (MMF), rapamycin (RAP) and lymphocyte depleting agents led to one-year graft survival rate in excess of 90% [4,5]. This extraordinary feat was, in part, due to the vast improvement in both surgical and organ preservation technologies. However in the last two decades, the steady increase in life span of renal transplant has been driven principally by the attrition rate in the first year. Due to inadequate immunosuppression and/or drug-induced nephrotoxicity, long-term allograft survival has been less satisfactory [4]. Thus rate of deceased donor graft loss in the first year dropped from 20% in 1989 to 7% in 2008, but it remained steadily constant at 5-7% over the same period for those that survived beyond one year [6]. Steroids Minimization Strategies United States registry data showed that more than 25% of the patients who are discharged from hospital after the transplant surgery have had a successful discontinuation of steroids treatment [6]. Although there is no consensus on the nomenclature for minimization strategies, for simplicity we shall use the following definitions: i) Steroid free: A strict definition of a complete elimination would imply...

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Reduced-dose Cyclosporine with Mycophenolate Mofetil and Prednisone Significantly Improves the Long-term Glomerular Filtration Rate and Graft Survival

Cited by 2 publications

References 26 publications

Metabolic consequences of modern immunosuppressive agents in solid organ transplantation

Metabolic consequences of modern immunosuppressive agents in solid organ transplantation

A Critical Review of Steroid Immunotherapy in Kidney Transplantation

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