Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunosuppressive benefits of cyclosporine and tacrolimus in short-term and medium-term renal allograft survival are well documented. It is becoming increasingly clear that the basis of this immunosuppression, the inhibition of calcineurin, may be linked with nephrotoxicity, hypertension, hyperlipidemia, and new-onset diabetes mellitus, side effects that may lead to CRAD, death due to CVD, and late renal allograft loss. This clinical picture presents a clear need for new strategies that produce adequate immunosuppression to prevent acute rejection while simultaneously reducing the side effects associated with CNI-related therapies. Sirolimus combined with cyclosporine and tacrolimus has demonstrated an ability to reduce incidences of early acute rejection and, used as base therapy, has provided protection against acute rejection equivalent to that of cyclosporine, without the consequent nephrotoxicity associated with CNIs. In preliminary results from an ongoing clinical trial, sirolimus has been used to eliminate cyclosporine during maintenance immunosuppression, with subsequent improvements in measures of blood pressure and renal function. In addition, the antiproliferative properties of sirolimus and its ability to prevent graft vascular disease in animal studies make sirolimus a promising agent to decrease incidences of CRAD and improve long-term renal allograft survival. These findings point to a clear need to further explore both the efficacy of sirolimus immunotherapy and its long-term effects.
...
PMID:Exploring treatment options in renal transplantation: the problems of chronic allograft dysfunction and drug-related nephrotoxicity. 1158 88

The use of calcineurin inhibitors (CNIs; cyclosporine and tacrolimus) has dramatically increased medium-term life expectancy after heart transplantation but has had only limited impact on long-term outcomes for heart transplant recipients. The original oil-based formulation of cyclosporine has been superceded by a microemulsion formulation (Neoral), which has more predictable pharmacokinetics and allows more precise dose-tailoring. Cyclosporine microemulsion and tacrolimus (Prograf) have a similar efficacy in the prevention of acute rejection of heart transplants, but their use is accompanied by nephrotoxicity and by cardiovascular side effects. The efficacy of immunosuppression can be improved by adjunctive therapy, such as azathioprine, mycophenolate mofetil (MMF; Cellcept), corticosteroids, and induction therapy. One of the most important predictors of patient mortality at >5 years after heart transplantation is cardiac allograft vasculopathy (CAV)/late graft failure, which accounts for 31% of deaths. Neither cyclosporine nor tacrolimus have been shown to prevent the development of CAV. In terms of efficacy, MMF provides a modest advantage over azathioprine in preventing CAV, and the combination of cyclosporine plus MMF results in significantly lower mortality than cyclosporine plus azathioprine. Overall, CNIs have multiple cardiovascular side effects, such as hypertension, hyperlipidemia and new-onset diabetes after transplantation, although cyclosporine and tacrolimus have somewhat different cardiovascular side-effect profiles. The challenge in choosing the best immunosuppressive regimen is to balance efficacy and safety to optimize graft and patient survival over the course of many decades. Because cyclosporine and tacrolimus have similar efficacy against acute rejection the choice of CNI for heart transplant recipients should be based on the relative risk of cardiovascular and renal side effects.
...
PMID:Calcineurin inhibitors in heart transplantation. 1509 6

We started using polyclonal antibody preparations (Thymoglobuline and Lymphoglobuline) as well as cyclosporine in 1981. A sequential immunosuppressive protocol was designed consisting of induction, delay cyclosporine introduction and corticosteroid withdrawal within the first 3 post-transplant months. This new immunosuppressive regimen has been applied to 1,671 patients: 1,439 received Thymoglobuline and 232 Lymphoglobuline; 1,083 were recipients of a primary renal transplant, 282 of a second transplant, 52 of third or fourth transplants, and 254 were recipients of a simultaneous kidney-pancreas transplant. The great majority of patients (96%) were recipients of cadaver organs; their age ranged from 3 to 77 years (average, 43+/-14). The overall incidence of acute rejection (intent-to-treat and biopsy-proven) was 23.7% (16% of patients had one episode and 8% had more than one episode), with 6.5% of rejections occurring after the third month and 3% after 12 months. The incidence of corticosteroid-resistant rejection was 8.7%. Between 1981 and 1990 (azathioprine maintenance) 40% of patients experienced an acute rejection while receiving a primary transplant versus 44% in case of retransplantation. Between 1991 and 1995 (CsA microemulsion maintenance), these percentages were reduced to 30 and 16%. After 1996 (mycophenolate mofetil and calcineurin inhibitors maintenance), the incidence of acute rejection was dramatically reduced to 8 and 6%, respectively in primary and retransplants. The incidence of patients free of corticosteroids was 61% at 3 months, 74% at 6 months, 79% at 1 year, 82% at 2 years, 89% at 5 years, 94% at 10 years and 100% at 20 years. A statistically better graft survival (up to 20 years, with similar patient survival) was observed in patients treated with Thymoglobuline as compared to Lymphoglobuline. Similar graft survival was observed in recipients of primary transplants as compared to retransplantation. The overall incidence of PTLD was 2.3%, with a significant decrease over the years achieving 0% after 1999. Thymoglobuline induction is a safe and highly efficient therapy to prevent rejection after kidney and kidney-pancreas transplantation. In association with CNI and antiproliferative immunosuppressive drugs, Thymoglobuline allowed the safe and early withdrawal of corticosteroids. This strategy of minimization of immunosuppression may have several beneficial effects in the long term.
...
PMID:Prevention of acute rejection with antithymocyte globulin (Thymoglobuline): its potential to reduce corticosteroids. 1559 85

Immunosuppressant agents have greatly increased graft and overall survival in heart transplant patients, but some of these agents (e.g., calcineurin inhibitors [CNI] and corticosteroids) can also induce adverse events that may contribute to cardiac allograft vasculopathy (CAV) (e.g., nephrotoxicity and cytomegalovirus infection). The current trend is therefore toward CNI- and steroid-sparing regimes. This study reports on the initial clinical experience with Certican (everolimus), a novel proliferation signal inhibitor with immunosuppressant properties that has been shown to prevent or delay CAV. Seven de novo heart transplant patients were treated at our center. Patients received cyclosporine for microemulsion (CsA; Neoral), corticosteroids and fluvastatin in addition to everolimus. Mean everolimus blood trough levels were maintained within the target range of 3 to 8 ng/ml throughout the first 14 weeks post-transplant. CsA was initiated at a reduced dose, and by Weeks 8 to 14 the mean trough blood level was 187.7 ng/ml. The combination of everolimus and reduced-dose CsA was not associated with increased incidence of biopsy-proven acute rejection (BPAR). Two patients did experience BPAR, but only very mildly (ISHLT Grade 1A). The mean creatinine level pre-transplant was 1.5 mg/dl; this increased to 2.0 mg/dl at 2 weeks post-transplant, but returned to near baseline levels during Weeks 8 to 14 (1.66 mg/dl). Some patients had elevated blood lipids. Patients receiving everolimus should have lipid levels monitored on a regular basis. Everolimus may allow optimization of immunosuppressant regimens in de novo heart transplant patients so that adequate efficacy can be achieved with reduced CNI exposure, thereby protecting kidney function.
...
PMID:Clinical experience with Certican (everolimus) in de novo heart transplant patients at the Deutsches Herzzentrum Berlin. 1577 23

Mycophenolate mofetil (MMF) introduction with concurrent reduction in calcineurin inhibitors has been shown to be beneficial in chronic allograft nephropathy (CAN) in adults. MMF was introduced to 19 children with CAN 26.3+/-5.8 (range 3.1-82.6) months after transplantation. Patients were followed up for a mean of 13.2+/-2.9 (range 1.2-51.1) months. The mean initial MMF dose was 660+/-56 mg/m2 per day, increased to 1,042+/-73 mg/m2 per day a year later. Cyclosporin was reduced from 138+/-10 mg/m2 per day at MMF introduction, to 116+/-15 mg/m2 per day at 6 months and 107+/-24 mg/m2 per day at 1 year. Six months prior to MMF introduction GFR deteriorated by -32.7+/-7.3 ml/min per 1.73 m2 per year. Six months after the introduction of MMF, GFR improved by +26.2+/-7.1 ml/min per 1.73 m2 per year (P <0.001). The introduction of MMF significantly reduced both the graft rejection rate (P=0.01) and systolic blood pressure (P=0.01), without a significant change in antihypertensive treatment. Haematological parameters did not significantly differ before and after MMF introduction. The introduction of MMF in paediatric renal transplant recipients with CAN may cause a significant improvement in GFR in both the short-term and the long-term and may well have a beneficial effect on systolic blood pressure. MMF has the potential to enable CNI-sparing protocols to be adopted.
...
PMID:Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients. 1613 52

Owing to the increasing disparity of organ demand and organ supply the search for optimal immunosuppressive strategies has become a central issue in kidney transplantation (KTX). In the focus today are modifications of the use of calcineurin-inhibitors (CNIs, Cyclosporine A/Tacrolimus) and steroids, as they are nephrotoxic and promote cardiovascular risk factors like arterial hypertension, hyperlipidemia and diabetes mellitus. These modifications can either be withdrawal or avoidance of these substances in combination with new and/or established immunosuppressants. Because about half of all KTXs are performed by or with the help of urologists' knowledge of modern immunosuppressive regimens is crucial also for urologists. We performed a literature research (PubMed, DIMDI, medline) for CNI- and steroid-sparing protocols and studies to elucidate their influence on graft-function and graft- and patient-survival. New substances and actual studies were also evaluated. Several published reports on CNI- and steroid-sparing protocols after KTX exist, including withdrawal, reduction or avoidance. The time of reduction seems to be crucial: an initially increased immune response should be counterbalanced by an initially intensified immunosuppression. Therefore, late steroid withdrawal seems to be safer than early withdrawal especially in Cyclosporine-based immunosuppression. Steroid avoidance also seems feasible on a CNI based regimen, especially in context with induction therapy. Withdrawal or avoidance of CNIs seems feasible with mycophenolate acid and/or induction therapy with IL 2-receptor antibodies as co-immunosuppressants. This is of interest in grafts with deteriorating function or from donors with extended criteria. Also, CNI- and steroid-free immunosuppression can be successfully performed with new immunosuppressants but results are yet premature. CNI- and/or steroid reduction, withdrawal or even avoidance is feasible. As long-term graft function is the goal of KTX and as more kidneys from donors with extended criteria are transplanted "tailored immunosuppression" will replace standards in the future.
...
PMID:Steroid- and calcineurin inhibitor free immunosuppression in kidney transplantation: state of the art and future developments. 1733 1

Intestinal perforation after lung transplantation is common in elderly patients with diverticulitis. The distal intestinal obstruction syndrome (DIOS) is a current complication in patients with cystic fibrosis. Myelosuppressive drugs as in most immunosuppressive regimens can cause cytopenia. Thrombotic microangiopathy is often caused by immunosuppressive regimen with a calcineurin-inhibitor in combination with a proliferation signal-inhibitor. Although renal failure and neurological symptoms are often additional side effects of the immunosuppressive therapy there are no reliable data on CNI-free protocols. Studies have shown that administration of statins is associated with improved function and survival of lung allografts.
...
PMID:[Complications after lung transplantation: gastroenterological, hematological and cardiovascular involvement]. 1839 93

In kidney transplantation patient and graft survival are excellent in short-term and mid-term, although they remain stable in the long-term.The incidence of acute rejection has decreased to 8%-15%.Despite marked progress in understanding immunologic mechanisms involved in transplantation, new tools are required to detect early changes that could affect allograft function allowing us to anticipate histological lesions and providing a more accurate use of immunosuppressive drugs.From an immunologic point of view, efforts should be directed to avoid interstitial fibrosis and tubular atrophy (IF/TA) and to prevent antibody-mediated rejection.The most frequent cause of late graft loss is IF/TA.Improvement in kidney transplant results have been achieved with calcineurin inhibitors -CNI- (cyclosporin and tacrolimus), antiproliferative agents (mycophenolate mofetil and enteric-coated mycophenolic acid) and T-cell depleting antibodies. The combination of tacrolimus + mycophenolate mofetil + steroids has been the gold standard in kidney transplant immunosuppression. An adequate balance in order to maintain the appropriate immune response is essential to the patient to avoid infections or neoplasias as well to prevent rejection.In renal transplant recipients with chronic kidney disease stage 4T in which renal function remains stable,immuno-suppressive drugs can be continued at the usual maintenance doses. As GFR declines, CNI and antiproliferative drugs should be reduced.
...
PMID:[Progression factors in chronic kidney disease. Immunological mechanisms]. 1967 56

The term chronic allograft nephropathy (CAN) was originally coined in 1991 to replace chronic rejection which was used too generalized. However, the revised Banff classification, published in 2007, eliminated the term CAN again because it was felt that the term was used too broadly and prevented the search for the underlying cause. Interstitial fibrosis and tubular atrophy are integral parts of chronic allograft dysfunction and represent in the new classification a separate entity with or without the identification of a specific etiology. Myofibroblasts are the key, albeit not exclusive, effector cells in renal fibrogenesis resulting in upregulated extracellular matrix synthesis and eventually in interstitial fibrosis. These cells are formed mainly by stimulation of resident interstitial fibroblasts but also by differentiation processes of periadventitial cells, bone marrow derived cells and by a process entitled epithelial mesenchymal transition (EMT) of tubular epithelial cells. EMT has been described by many groups to be of high prevalence in renal allograft dysfunction contributing to matrix accumulation and renal function deterioration. This is of particular interest because immunosuppressive therapy has differential effects on EMT with calcineurin inhibitors in particular inducing the process. Moreover, specific therapies inhibiting EMT have been applied in experimental studies although the effects of their application in chronic allograft dysfunction remain to be studied. At the same time, immunosuppression may interfere with physiologic clearance of myofibroblasts by apoptosis, explaining in part the high prevalence of interstitial fibrosis in allograft biopsies. The Fas system has been identified to be mainly responsible for this physiologic apoptosis in non-renal scarring models; however, its relevance for renal fibrosis and particular fibrosis in renal allograft dysfunction remains to be determined. These findings point to a cautious and individualized use of immunosuppressive therapy in patients with allografts and particular those with chronic allograft dysfunction not because of rejection processes. Protocols using CNI-free immunosuppression are interesting options to prevent fibrosis in chronic allograft dysfunction.
...
PMID:Pathogenesis of tubulointerstitial fibrosis in chronic allograft dysfunction. 1993 Mar 13

Since liver transplantation was approved for the treatment of end stage liver disease, calcineurin inhibitors (CNI's) have played a critical role in the preservation of allograft function. Unfortunately, these medications cause a variety of Side effects such as diabetes, hypertension and nephrotoxicity which in turn result in significant morbidity and reduced quality of life. A variety of newer immunosuppressants have been evaluated over the last decade in an attempt to either substitute for CNI's or use with reduced dose CNI's while still preserving allograft function However, current data does not recommend complete cessation of CNI's due to unacceptably high rates of allograft rejection. As these medications have their own unique adverse effects, a careful assessment on their risks and benefits is essential, particularly when additive or synergistic effects with CNI's may occur. Furthermore, the impact of these newer medications on the risk of hepatitis C recurrence and progression remains to be elucidated. Controlled trials are urgently required to assist transplant physicians with choosing the optimum immunosuppressive regimen for their patients. This review will discuss commonly used immunosuppressants prescribed in liver transplantation, emerging therapties and where appropriate, the impact of these medications on the recurrence of hepatitis C after liver transplantation.
...
PMID:A comprehensive review of immunosuppression used for liver transplantation. 2013 Jul 72


1 2 3 Next >>

---