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

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

Two forms of post-transplant thrombotic microangiopathy (TMA) may be recognized: recurrent TMA and de novo TMA. Recurrent TMA may occur in patients who developed a nondiarrhoeal form of haemolytic uraemic syndrome (HUS) being particularly frequent in patients with autosomal recessive or dominant HUS. The recurrence is almost the rule in patients with mutation in complement factor H gene. Most patients eventually lose the graft. Treatment with plasma infusions or plasmapheresis is often disappointing, but few cases may be rescued. Intravenous immunoglobulins and rituximab have also been successful in anedoctic cases. De novo TMA is rarer. A number of factors including viral infection may be responsible of de novo TMA, but in most cases TMA is triggered by calcineurin inhibitors or mTOR inhibitors. The clinical presentation of de novo TMA may be variable with some patients showing clinical and laboratory features of HUS while others showing only a progressive renal failure. The prognosis is less severe than with recurrent TMA. Complete withdrawal of the offending drug may lead to improvement in many cases. The addition of plasma exchange may result in graft salvage in about 80% of cases.
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PMID:Thrombotic microangiopathy after kidney transplantation. 1696 69

Immunosuppressive protocols in dual kidney transplantation (DKT) are based on calcineurin inhibitors (CNI). We wonder whether a CNI-free immunosuppression can improve outcome in older patients receiving a DKT with marginal donor organs. Thirty-six were treated with CsA, MMF and prednisone (CsA group) and 42 with rATG, SRL, MMF and prednisone (SRL group). Incidence of delayed graft function and acute rejection was 44% and 11% in the CsA group, and 40% and 8% in the SRL group. CMV infection incidence was low in both protocols. Three-year patient survival was 89% in the CsA and 76% in the SRL group. One- and 3-year graft survival after censoring for dead with a functioning allograft was 94.2% and 94% in CsA and 95% and 90% in SRL, respectively. Renal function was similar in both groups whereas proteinuria was higher in the SRL group. Uninephrectomy due to graft thrombosis or urinary-related complications was numerically higher in the SRL (21%) than in the CsA group (8%) (p = 0.13) and it was associated with renal failure and proteinuria. In DKT, a new induction immunosuppressive protocol based on rATG, SRL, MMF and prednisone does not offer any advantage in comparison to the old CsA, MMF and prednisone.
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PMID:Immunosuppression for dual kidney transplantation with marginal organs: the old is better yet. 1721 33

Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P=.048). The overall mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P=.023), renal failure at baseline (P=.028), fungemia (P=.006), and disseminated infection (P=.035) and was lower in those receiving a calcineurin-inhibitor agent (P=.003). In a multivariable analysis, the receipt of a calcineurin-inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P=.008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P=.037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients.
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PMID:Cryptococcus neoformans in organ transplant recipients: impact of calcineurin-inhibitor agents on mortality. 1726 20

Many patients receiving allogeneic stem cells develop chronic graft-versus-host disease (cGVHD), which remains as the main cause of morbidity and mortality. Although the first line of therapy is generally with steroids, it is not well known how to manage refractory cases. Those patients are usually treated with alternative experimental agents. Sirolimus (Rapamycin), a new immunosuppressive agent, inhibits signal transduction and cell cycle progression after binding to FKBP12. We report a retrospective analysis with sirolimus in transplant recipients with cGVHD refractory to previous immunosuppressive therapy. Forty-seven patients with refractory or relapsed cGVHD were treated with the combination of sirolimus and calcineurin inhibitors (n = 33), mycophenolate (n = 9), or prednisone (n = 5). Thirty-eight of 47 (81%) patients had clinical responses (complete = 18, partial = 20). The main toxicity was mild renal failure, particularly at the start of therapy. Four patients who presented thrombotic microangiopathy were managed with plasmapheresis and the discontinuation of sirolimus and calcineurin inhibitors. Statistical analysis showed the type of cGVHD onset and presirolimus clinical status as the main variables influencing the response to treatment. The Kaplan-Meier estimate of survival was 57.4% at 3 years. The current study shows the efficacy and safety of sirolimus in refractory cGVHD patients. Further investigation is warranted to elucidate the role of sirolimus in cGVHD, and find the best combination (sirolimus + calcineurin inhibitors versus others) for therapeutic use.
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PMID:Sirolimus as part of immunosuppressive therapy for refractory chronic graft-versus-host disease. 1753 80

Five heart recipients were followed up with mycophenolate mofetil and low dose cyclosporine due to progressive severe chronic postcyclosporine renal failure. Cyclosporine was gradually withdrawn and finally eliminated from immunosuppressive regimen to slow the rate of renal function loss. Improvement of renal function was observed. In the follow up after cyclosporine elimination no risk increase of acute rejection and no deterioration of left ventricle function was observed. Non-calcineurin inhibitors model in heart recipients can be the treatment of choice (but only in very selective cases) in patients with severe chronic renal insufficiency.
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PMID:Discontinuation of calcineurin inhibitors in heart transplant patients with end stage renal insufficiency as an alternative model of immunosuppression. 1764 34

Kidney transplantation is considered the best treatment for patients with end-stage renal failure, even in extreme age-groups. Immunosuppression for "life" is, however, mandatory. This chronic, somewhat unselected, inhibition of the host immune system may induce complications, such as cancer and infection, that could counterbalance the benefits achieved by the transplant. In addition, all currently used immunosuppressors have several side-effects, impeding their long-term use. Consequently, drug associations are frequently tested by different centres according to their own practices, resulting in different survival and tolerance profiles. Corticosteroids and calcineurin inhibitors are the cornerstones of current immunosuppressive regimens. However, they are also the main culprits of adverse-events and side-effects encountered after transplantation. Lowering the doses of each drug, or even eliminating them from the immunosuppressive menu, has been evaluated by many groups over the last two decades. This review summarises a huge number of studies dealing with corticosteroid and calcineurin inhibitor minimization, including withdrawal and avoidance trials. It is hard today to propose any practical guidelines on such a controversial topic. Good results are achieved by some groups and bad results by others. The lack of long-term follow-up in randomized studies contributes to this debate. Nevertheless, it seems possible and safe to avoid corticosteroids and/or calcineurin inhibitors in many patients. The application of protocol biopsies as well as new immunological tests to determine the degree of immunosuppression will certainly help transplant physicians to provide more personalized treatment strategies.
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PMID:Immunosuppression minimization in kidney transplantation. 1798 39

The authors review the case of their young patient, who underwent a lung transplantation in Vienna because of an end stage idiopathic pulmonary fibrosis. During the prolonged postoperative phase renal failure full of complications developed, which necessitated haemodialysis. As the pulmonological rehabilitation was complete, but the regular dialyses considerably raised the risk of opportunistic infections, and also significantly reduced the quality of life of the patient, renal transplantation was performed in Debrecen four years after the lung transplantation. This is the first lung transplanted patient in Hungary who also underwent renal transplantation. Now, more than two years after the renal transplantation the patient lives a compensated, rehabilitated life, the respiratory function values have improved and the renal function values are also acceptable. The number of transplanted patients has significantly increased in recent years worldwide, and also in Hungary. However, due to immunosuppressive medications, calcineurin inhibitors mainly, numerous complications must be reckoned with. An outstanding one among them is the secondary renal failure which may occur both in acute and chronic form and may even necessitate renal transplantation. Renal transplantation is an excellent treatment option for end stage renal failure patients, who had received another organ transplant earlier. Kidney transplantation improves quality of life and increases expected survival, too.
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PMID:[Successful renal transplantation following lung transplantation: a survey of the first Hungarian case]. 1798 27

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.
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PMID:[Complications after lung transplantation: gastroenterological, hematological and cardiovascular involvement]. 1839 93

Acute and especially chronic renal failure (CRF) are relatively common and important risk factor for morbidity and mortality in patients after heart, lung, liver or intestine transplantation. Numerous factors contribute to the development of CRF in this group of patients, like treatment with calcineurin inhibitors and other nephrotoxic drugs in the perioperative period, hemodynamical changes during and after the surgery, preexistent renal disease, hypertension, diabetes mellitus, dyslipidemia and anemia. Pretransplant evaluation of renal function is mandatory to predict which patients have increased risk for development of CRF. In the posttransplantation course it is necessary to timely diagnose and treat renal failure, while patients with insufficient renal function have 4.55-fold increased risk of death compared to patients with normal renal function. Special problem is diagnostic approach to patients with suspected chronic renal disease who are candidates for transplantation of other parenhimatose organs. Diagnostic value of serum creatinine and estimation of renal function based on its value is very limited. Gold diagnostic standard is radioisotope estimation of glomerular filtration, but this method is not widely available. It seems that this problem may be solved with the use of cystatin C, but this approach needs to be validated in large studies. Numerous different immunosuppressive drugs available on the market enable individualization of immunosuppression. Different drugs combinations may have less nephrotoxic potential, but one must be careful because of the possible risk of organ rejection with the change of immunosuppression. Use of angiotensin convertase enzyme inhibitors and/or angiotensin receptor blockers, statins with drugs for control of hyperglycemia, may prevent or postpone development of CRF. Although technical advances of contemporary hemodialysis machines and peritoneal dialysis equipment enable well tolerated dialysis even in critically ill patients, renal transplantation remains the method of choice for treatment of patients with transplanted parenhimatous organ that developed CRF.
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PMID:[Chronic renal failure after heart, lung, liver, or intestine transplantation]. 1857 34

For patients with end-stage kidney failure, kidney transplantation improves both their quality of life and overall life expectancy compared with dialysis, but it is not without adverse effects. Cancer is second to cardiovascular disease as one of the major causes of morbidity and mortality in renal transplant recipients. Prolonged use of modern immunosuppression, which leads to alteration of immune function and immune surveillance, is associated with increased cancer risk. There is now convincing evidence from observational studies and registry data to confirm a 3- to 5-fold increase in overall cancer incidence, with viral-related neoplasia incurring the greatest risk when compare with the general population. Despite the increased risk, little is known about the overall cancer prognosis, screening, treatment strategies, and effectiveness in this population. Cancers can recur, occur de novo, and be transmitted from donor organs posttransplantation. Uncertainties exist as to how modern immunosuppressive agents impact on cancer management and outcomes in these patients, with some agents such as calcineurin inhibitors and azathioprine, being more carcinogenic than others. The newer agents, proliferation signal/mammalian target of rapamycin inhibitors and mycophenolate mofitil, may have some antiproliferative and antitumor activities demonstrated in preclinical and clinical studies, but long-term well-powered trial data are needed to determine whether they are either protective or curative for cancers in renal transplant recipients. In this review, the incidence, etiology, prognosis, and potential approaches to cancer screening and management post-renal transplantation are discussed.
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PMID:Cancers after renal transplantation. 1863 67


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