Tacrolimus with Mycophenolate Mofetil (MMF) or Sirolimus vs. Cyclosporine with MMF in Cardiac Transplant Patients: 1-Year Report

Kobashigawa, Jon A.; Miller, Leslie W.; Russell, Stuart D.; Ewald, Gregory A.; Zucker, Mark; Goldberg, Lee R.; Eisen, Howard J.; Salm, K.; Tolzman, D.; Gao, Jinwu; Fitzsimmons, William E.; First, Roy

doi:10.1111/j.1600-6143.2006.01290.x

Cited by 296 publications

(185 citation statements)

References 25 publications

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“…Moreover, the fibrogenic potential of tacrolimus also appears to be lower (210), although these results could not be confirmed in a more recent study (135). In nonrenal solid organ transplantation, there are singleand multicenter studies as well as registry analyses demonstrating the benefit of tacrolimus over cyclosporine with regard to renal function (24, [211][212][213][214], although other studies did not observe this benefit of tacrolimus over cyclosporine (215).…”

Section: Comparison Between Cyclosporine and Tacrolimusmentioning

confidence: 99%

Calcineurin Inhibitor Nephrotoxicity

Naesens

Kuypers²,

Sarwal³

2009

Clinical Journal of the American Society of Nephrology

1,241

1,000

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The use of the calcineurin inhibitors cyclosporine and tacrolimus led to major advances in the field of transplantation, with excellent short-term outcome. However, the chronic nephrotoxicity of these drugs is the Achilles' heel of current immunosuppressive regimens. In this review, the authors summarize the clinical features and histologic appearance of both acute and chronic calcineurin inhibitor nephrotoxicity in renal and nonrenal transplantation, together with the pitfalls in its diagnosis. The authors also review the available literature on the physiologic and molecular mechanisms underlying acute and chronic calcineurin inhibitor nephrotoxicity, and demonstrate that its development is related to both reversible alterations and irreversible damage to all compartments of the kidneys, including glomeruli, arterioles, and tubulo-interstitium. The main question-whether nephrotoxicity is secondary to the actions of cyclosporine and tacrolimus on the calcineurin-NFAT pathway-remains largely unanswered. The authors critically review the current evidence relating systemic blood levels of cyclosporine and tacrolimus to calcineurin inhibitor nephrotoxicity, and summarize the data suggesting that local exposure to cyclosporine or tacrolimus could be more important than systemic exposure. Finally, other local susceptibility factors for calcineurin inhibitor nephrotoxicity are reviewed, including variability in P-glycoprotein and CYP3A4/5 expression or activity, older kidney age, salt depletion, the use of nonsteroidal anti-inflammatory drugs, and genetic polymorphisms in genes like TGF-␤ and ACE. Better insight into the mechanisms underlying calcineurin inhibitor nephrotoxicity might pave the way toward more targeted therapy or prevention of calcineurin inhibitor nephrotoxicity.Clin J Am Soc Nephrol 4: 481-508, 2009. doi: 10.2215/CJN.04800908 T he introduction of the calcineurin inhibitor (CNI) cyclosporine in human kidney transplantation in the late 1970s revolutionized transplantation medicine, and made transplantation a preferable therapeutic intervention for end-stage renal diseases (1,2). In 1984, the potent immunosuppressive properties of another CNI, tacrolimus, were discovered, and tacrolimus was used successfully in human liver, kidney, and heart allograft recipients (3,4). Currently, 94% of kidney transplant recipients are discharged after transplantation with a CNI-based immunosuppressive regimen (5).The immunosuppressive properties of cyclosporine and tacrolimus result from inhibition of calcineurin, a calcium-and calmodulin-dependent phosphatase (protein phosphatase 3 [PPP3C], formerly PP2B). Intracellularly, these completely different molecules bind to cyclophylin and FKBP12 for cyclosporine and tacrolimus, respectively (6 -9). The competitive binding of cyclosporine-cyclophylin and tacrolimus-FKBP12 complexes to calcineurin inhibits phosphatase activity of calcineurin. This inhibition then suppresses the transcription of IL-2 via inhibition of the dephosphorylation and impaired translocation of the nucl...

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Section: Comparison Between Cyclosporine and Tacrolimusmentioning

confidence: 99%

Calcineurin Inhibitor Nephrotoxicity

Naesens

Kuypers²,

Sarwal³

2009

Clinical Journal of the American Society of Nephrology

1,241

1,000

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“…Some studies have shown higher incidence of infection in diabetic cardiac transplant patients compared to nondiabetic patients [129]. Discrepancies in the results of these studies are attributed to the limitations including defining criteria for the diagnosis of diabetes, therapeutic regimen used for the management of diabetes, target glycemic control and presence of any associated micro or macrovascular complications of diabetes [131,137,138]. Further studies are required to define the therapeutic targets and impact of glycemic control on development and prognosis of CAV.…”

Section: Diabetes Mellitusmentioning

confidence: 99%

“…There is a high prevalence of hypertension and other metabolic abnormalities in patients with renal dysfunction. CNIs affect the glomerular filtration and are identified as nephrotoxic agents [131]. Ischemic etiology of end stage heart disease prior to transplantation has been associated with increased risk of CAV.…”

Section: Other Non-immunologic Risk Factorsmentioning

confidence: 99%

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Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

Munagala¹,

Phancao²

2018

obm.transplant

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Heart transplant remains the gold standard therapy for patients with end stage heart disease and offers improved survival and quality of life. Significant progress has been achieved in improving one-year mortality after heart transplantation. Nonetheless, longterm graft survival has not changed significantly over the past few decades. Long term survival of heart transplant recipients is limited by chronic rejection, cardiac allograft vasculopathy (CAV), and malignancy. CAV is a major contributor for graft failure and mortality after the first year of in heart transplant recipients. CAV is a proliferative vasculopathy characterized by diffuse myointimal hyperplasia and progressive narrowing of the graft vessels. Both immune dependent and independent factors have been shown to contribute to the pathogenesis of CAV. Understanding these risk factors is essential in developing preventative and therapeutic strategies. Angiography with Intravascular ultrasound has become the key diagnostic tool in the early detection of CAV as well as prognostication. Echocardiographic assessment of allograft function in conjunction with coronary angiographic findings are used in assessing the severity of CAV. Adjustment of immunosuppression and statins remain the initial steps in the management of CAV. Retransplantation is the definitive treatment for severe CAV, however, the paucity of organs along with increased mortality associated with retransplantation makes it a less desirable option. Remarkable progress has been achieved in the understanding of pathogenesis, risk factors for CAV and plaque morphology. Nevertheless, significant knowledge gaps persist in scientific understanding of risk factors, pathogenesis, prevention and treatment of CAV. Further research is warranted to fill these gaps, develop diagnostic modalities to facilitate early detection of CAV, and management strategies to Improve graft tolerance and immune modulation. This review focuses on summarizing the pathogenesis and risk factors for CAV.

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“…The reason for conversion from CSA to Tac for 7 patients was to allow optimization of immunosuppression due to recurrent rejection, because previous reports had revealed a superiority of Tac over CSA for treating rejection and graft survival. 25,26) One patient required conversion from CSA to Tac due to reversible posterior leukoencephalopathy, which occurred immediately after transplantation when the patient was treated with CSA. 27) One patient was weaned from calcineurin inhibitors to avoid the risk of developing posttransplant lymphoproliferative disorder; this patient showed an elevation of human Epstein-Barr virus DNA.…”

Section: Patient Characteristics and Surgical Proceduresmentioning

confidence: 99%

Clinical Course and Outcome of Heart Transplant Recipients Single Center Experience at the National Cardiovascular Center in Japan

et al. 2010

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SummaryThe number of heart transplant (HTx) surgeries in Japan is expected to increase under the Revised Organ Transplant Law. To date, among 69 HTx surgeries performed in Japan, 27 operations (39.1%) were performed at our institution, the National Cardiovascular Center (NCVC), located in Osaka. We have reviewed the outcomes of HTx conducted at NCVC during a 10 year period (May 1999 to January 2009). Among 27 heart transplant recipients at NCVC, the clinical charts of 26 recipients whose post-HTx period exceeded 1 year were retrospectively reviewed and compared to data from the International Society for Heart and Lung Transplantation (ISHLT) Registry. The survival rate of our recipients was 96.2% at 10.8 years, which was excellent even compared to the ISHLT Registry. The immunosuppressive regimen at NCVC was equivalent to that of the ISHLT Registry, except for more frequent use of Muromonab-CD3 (26.9% versus 3.3%, P < 0.0001) and an initial CSA-based regimen (65.3% versus 34.4%, P < 0.001). The drug we use for induction therapy has been recently changed from Muromonab-CD3 to Basiliximab. The incidences of post-HTx hypertension, diabetes, hyperlipidemia, and renal insufficiency were significantly less in patients at NCVC compared to those in the ISHLT Registry, however, the incidence of transplant coronary artery disease (TxCAD) was almost identical. Clinical review of post-HTx outcome at NCVC can provide useful information for Japanese transplant cardiologists who will engage in HTx management. (Int Heart J 2010; 51: 264-271)

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Tacrolimus with Mycophenolate Mofetil (MMF) or Sirolimus vs. Cyclosporine with MMF in Cardiac Transplant Patients: 1-Year Report

Abstract: suggest that the TAC/MMF combination appears to offer more advantages than TAC/SRL or CYA/MMF in cardiac transplant patients, including fewer ≥3A rejections or hemodynamic compromise rejections and an improved side-effect profile.

Cited by 296 publications

References 25 publications

Calcineurin Inhibitor Nephrotoxicity

Calcineurin Inhibitor Nephrotoxicity

Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

Clinical Course and Outcome of Heart Transplant Recipients Single Center Experience at the National Cardiovascular Center in Japan

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