Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, are widely used in pediatric liver transplant recipients and currently data are limited with regards to long-term results using the one drug or the other in comparable low doses. We conducted the present study to assess the advantages and disadvantages of both drugs in children at least five yr post-liver transplantation. A total of 129 children were enrolled in the study. Thirty-eight of the children were switched to tacrolimus monotherapy for different reasons [steroid resistant graft rejection (n = 15), chronic rejection (n = 5), severe acute rejection (n = 4), repetitive acute graft rejection (n = 5), dysfunction of the transplant (n = 3), insufficient CsA metabolism (n = 3), hypertrichosis (n = 2), and CsA toxicity (n = 1)], four patients had primary tacrolimus therapy, and 87 patients are receiving cyclosporine. Mean trough levels were 5.3 +/- 2.3 ng/mL (tacrolimus) and 73.6 +/- 44.5 micro/L (cyclosporine), respectively at least five yr post-orthotopic liver transplantation (OLT). There was no significant difference in the calculated glomerular filtration rate between children on cyclosporine and tacrolimus (142.7 + 39.5 mL/min/1.73 m(2) vs. 151.1 +/- 44.1 mL/min/1.73 m(2)). The incidence of arterial hypertension was 7.1% vs. 9.2%, that of hepatotoxicity was 0% vs. 2.3%. Cosmetic changes were found in more than one-third of the patients on cyclosporine and in 4.8% of the patients receiving tacrolimus. Quality of life was excellent in both groups (self assessment). The impact of CNIs on chronic graft dysfunction cannot be assessed by our present study. We conclude from the results that cyclosporine and tacrolimus are both excellent drugs for maintenance immunosuppression in the long-term course following pediatric liver transplantation. However, this retrospective analysis is limited by the bias between children on CsA as compared with patients receiving tacrolimus. A prospective randomized controlled trial is needed in order to assess which CNI is the best for children following OLT.
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PMID:Long-term evaluation of cyclosporine and tacrolimus based immunosuppression in pediatric liver transplantation. 1709 62

Tacrolimus is a calcineurin inhibitor recently approved in the US and throughout the EU for the prevention of allograft rejection in heart transplant recipients. It is commonly administered orally for long-term immunosuppression. The incidence of mild to severe acute rejection in the first 6 months following heart transplantation was significantly lower in tacrolimus recipients than in ciclosporin recipients (54% vs 66%) in a large, phase III trial conducted in Europe. A large, phase III trial conducted in the US did not show a significant difference between tacrolimus and ciclosporin in the incidence of severe rejection or haemodynamic compromise rejection requiring treatment within the first 6 months post-transplant (22% vs 32%), but did show a significant difference in the incidence at 1 year (23% vs 37%). In phase III trials, 1-year patient survival was similar between tacrolimus and ciclosporin recipients in the EU (93% vs 92%) and the US (95% vs 90%). Tacrolimus was shown to be effective in the prevention of rejection in paediatric and African American heart transplant recipients. The tolerability profile of tacrolimus in heart transplant recipients was broadly similar to that of ciclosporin, although tacrolimus was usually associated with lower incidences of post-transplant hypertension and dyslipidaemia.
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PMID:Tacrolimus: in heart transplant recipients. 1713 9

Liver allograft recipients are at increased risk of death from cerebrovascular and cardiovascular disease. We propose the following strategy of risk-reduction, based on currently available literature. Lifestyle: standard advice should be given (avoidance of smoking, excess alcohol and obesity, adequate exercise, reduction of excess sodium intake). Hypertension: target blood pressure should be 140/90 mmHg or lower, but for those with diabetes or renal disease, 130/80 mmHg or lower. For patients without proteinuria, antihypertensive therapy should be initiated with a calcium channel blocker and for those with proteinuria, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker. If monotherapy fails to achieve adequate response, calcium channel blockers and ACE-inhibitors or angiotensin II receptor blockers should be combined. If hypertension remains uncontrolled, an alpha-blocker may be added. Consideration should be given to changing immunosuppression and avoiding use of calcineurin inhibitors. Diabetes: recipients should be regularly screened for diabetes. For patients with new-onset diabetes after transplant, stepwise therapy should be guided by HbA1c concentrations, as with type II diabetes mellitus. Hyperlipidemia: annual screening of lipid profile should be undertaken, with treatment thresholds and targets based on those advocated for the high risk general population. Dietary intervention is appropriate for all patients. A statin should be considered as the first line treatment to achieve specified targets. In patients receiving a calcineurin inhibitor, Pravastatin should be commenced at a dose of 10 mg/day. In patients receiving other forms of immunosuppression, pravastatin may be commenced at a dose of 20 mg/day. Liver tests should be monitored and patients warned to report myalgia. If monotherapy is inadequate, ezetimibe or a fibrate may be added. Consideration may be given to change in immunosuppression if combination lipid-lowering therapy proves inadequate.
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PMID:Reducing the risks of cardiovascular disease in liver allograft recipients. 1749 26

We performed a case-control study in renal transplant patients between 1998 and 2003 to identify risk factors for arterial hypertension over the medium term in pediatric patients undergoing renal transplantation. Three years after transplant, patients were classified into hypertensive or control groups. The following risk factors were analyzed: hypertension before transplant, glomerular filtration rate at sixth posttransplant month, acute rejection episodes, renal artery stenosis, accumulated prednisone and calcineurin inhibitor doses, presence of native kidneys, donor type (living or cadaver), body mass index at 1 year posttransplant, and glomerular disease as renal insufficiency etiology. Of 161 transplants, 124 fulfilled the inclusion criteria; 63 were hypertensive, and 61 were controls. Univariate analysis showed hypertension before transplant (52/63 vs. 27/61, p < 0.001), glomerulopathies (23/63 vs. 12/61, p = 0.001), glomerular filtration rate at 6 months (71 +/- 18 vs, 80 +/- 18 ml/min per 1.73 m(2), p = 0.003) as risk factors. A tendency to statistical significance was observed with regard to body mass index (SDS) in the first year (0.40 +/- 1.10 vs, 0.04 +/- 1.10, p = 0.072). Multivariate analysis showed statistical significance concerning previous hypertension and glomerular filtration rate at 6 months. Hypertension before transplant and early graft function are the major risk factors for hypertension in the medium term following renal transplant.
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PMID:Risk factors for hypertension 3 years after renal transplantation in children. 1753 67

Calcineurin inhibitors (cyclosporine and tacrolimus) have been used as the mainstay immunosuppressive therapy for solid organ and hematopoietic cell transplantations (HCT) to prevent allograft rejection and for prophylaxis and treatment of the chronic graft-versus-host disease. Adverse effects of these drugs include nephrotoxicity, hepatotoxicity, neurotoxicity, hypertension and gingival hyperplasia. Association of oral non-gingival soft tissue hyperplasia with calcineurin inhibitor therapy has only recently been recognized and is thought to occur infrequently. We present four cases of oral non-gingival inflammatory fibro-vascular hyperplasias attributed to the use of calcineurin inhibitors following solid organ transplantation and HCT. These lesions interfere with function and must be differentiated from other oral lesions, and therefore should be surgically excised.
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PMID:Calcineurin inhibitor-associated oral inflammatory polyps after transplantation. 1785 Apr 43

Acute rejection episodes are now as low as 5-20% in the first year after renal transplantation; however, graft half-life has remained almost unchanged in the last decade. This statistic is mainly attributable to the side effects of immunosuppression, with loss of allografts due to the chronic allograft nephropathy that is a consequence of calcineurin inhibitor toxicity or hypertension. Patient death due to cardiovascular events, infections and malignancy also contribute to allograft loss. The introduction of the inhibitors of the mammalian target of rapamycin sirolimus and everolimus in renal transplantation has increased the repertoire of immunosuppressive protocols substantially. They have a different mode of action and a different side effect profile (i.e. lower nephrotoxicity, less hypertension and less neoplastic potential) than the calcineurin inhibitors. The inhibitors of the mammalian target of rapamycin therefore provide an especially promising alternative for the maintenance immunosuppression after renal transplantation. This overview provides a summary of the current literature on inhibitors of the mammalian target of rapamycin, with a special focus on sirolimus.
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PMID:Sirolimus in renal transplantation. 1789 Feb 66

Cardiac transplantation has become an established intervention for end-stage heart disease. Clinical outcomes in older cardiac transplant patients have improved over the last decade and are almost similar to those in younger patients. Nevertheless, morbidity and mortality due to infections, cancer and chronic allograft vasculopathy remain problematic. On the other hand, older transplant patients seem to have lower incidences of acute rejection episodes than younger patients. Conventional immunosuppression with calcineurin-inhibiting drugs, azathioprine and corticosteroids is responsible for a number of adverse effects. Although these adverse effects can also be seen in younger patients, tolerance to these agents seems to decrease with increasing age. In particular, diabetes mellitus, osteoporosis and chronic renal insufficiency are associated with higher morbidity and mortality in older cardiac transplant patients. As the elderly become an ever-increasing segment of the cardiac transplant population, new and innovative immunosuppressive strategies will have to be developed and applied.Currently, the availability of new immunosuppressive drugs means more individualised immunosuppressive protocols can be used. New antibodies for induction therapy, a choice between ciclosporin and tacrolimus, and the advent of mycophenolate mofetil as well as proliferation signal inhibitors (everolimus, sirolimus) have changed immunosuppressive protocols dramatically. Therefore, a generalised protocol for all patients has been replaced by individualised immunosuppression depending on the patient group. Moreover, protocols can be modified during follow-up depending on the individual patient's requirements and problems. Hypertension and hyperlipidaemia could be influenced by the selection of tacrolimus over ciclosporin, and weaning of corticosteroids might have a positive impact on osteoporosis or diabetes. There is also no clear evidence that tacrolimus is associated with a higher risk for new onset of diabetes. Chronic renal insufficiency can be managed with calcineurin inhibitor-free immunosuppression consisting of mycophenolate mofetil and proliferation signal inhibitors. Both everolimus and sirolimus also seem to have a protective effect against the onset of graft vasculopathy and some sorts of cancer after cardiac transplantation. As a general rule, however, older cardiac transplant patients should be treated with lower doses and fewer immunosuppressive drugs to avoid over-immunosuppression.
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PMID:Immunosuppressive therapy in older cardiac transplant patients. 1795 59

Similar to adults, CKD may persist after pediatric RTx. Clinical and laboratory parameters were analyzed retrospectively in 23 RTx recipients (13 males, age 11.9 +/- 5.2 yr), initially treated with prednisone, calcineurin inhibitor (TAC = 18, cyclosporine neoral = 5), and MMF at four months post-RTx (T1) and at 3.4 +/- 2.8 yr post-RTx (T2). Mean (+/-s.d.) cystatin C GFR (mL/min/1.73 m(2)) was 72 +/- 19 at T1 and 70 +/- 22 at T2 (NS). At T2, CKD stage I was present in five patients (22%), stage II in eight patients (35%), and stage III in 10 patients (43%). At T2, calcineurin inhibitors were utilized in 19, MMF in 13, and SIR in 13 patients. The prevalence of hypertension was 69% at T1 and 87% at T2 (p = NS). Anemia was diagnosed in 61% at T1 and 69% at T2 with average therapeutic MMF (2.78 +/- 1.3 mg/mL) and SIR (7.62 +/- 2.3 mg/mL) trough levels. Hypercholesterolemia was detected in 44.0% at T1 and 47% at T2. Bone disease was diagnosed in 26.0% at T1 and 21.7% at T2. Mean height Z-scores were -1.0 +/- 1.2 (T1) and -1.0 +/- 1.59 (T2, NS), with 21% at T1 and 30% at T2 below two SDS. We observed suboptimal growth, hypertension, hypercholesterolemia, bone disease, and anemia in a significant proportion of transplanted children.
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PMID:Complications of chronic kidney disease in children post-renal transplantation - a single center experience. 1818 92

Despite dramatic improvements in immunosuppression, late graft loss after kidney transplantation remains a common and difficult problem. Histologic evaluation may reveal changes related to BK polyomavirus infection, hypertension, or calcineurin inhibitor toxicity, which can help to guide therapy. The designation chronic allograft nephropathy should thus be reserved for biopsies with tubular atrophy and interstitial fibrosis without an apparent cause. Although the cause clearly includes both antigen-dependent and antigen-independent events, the approach remains largely to exclude immune mechanisms. Although this review discusses the potential contribution of antibody to chronic injury, it focuses on the basic elements of kidney injury, the role of parenchymal cells in promoting injury, and the proliferative and inflammatory responses that accompanying injury. Strategies to manage these recipients include close attention to accompanying hypertension, diabetes, and hyperlipidemia, as well as consideration for altering immunosuppression; however, therapies that limit epithelial-to-mesenchymal transition or directly block fibrosis pathways may reduce chronic allograft fibrosis and may prove to be useful. Understanding the basic pathogenesis sufficiently to allow early intervention may finally benefit patients who are at high risk for tubular atrophy and interstitial fibrosis and promote their long-term graft function.
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PMID:Late kidney allograft loss: what we know about it, and what we can do about it. 1830 4

Accumulating evidence suggests an important role of the calcineurin signaling pathway in mediating the development of cardiac hypertrophy. It has also been reported that angiotensin-converting enzyme inhibitors (ACEIs) regressed cardiac hypertrophy in some animal and human models. In this study, we investigated the possible role of calcineurin in the regression of cardiac hypertrophy induced by the ACEI perindopril in rats with renovascular hypertension. The effect of the calcineurin inhibitor cyclosporine A (CsA) was also studied. Starting from 2 months after a two-kidney one-clip (2K1C) procedure, the rats that had developed progressive left ventricular (LV) hypertrophy were daily administered perindopril (1 mg/kg per day) or CsA (20 mg/kg per day) until 3 months. At the end of either treatment, the LV gravimetric, morphometric and histological measurements revealed the regression of LV hypertrophy; and the enzymatic assay, Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) showed that both calcineurin activity and the calcineurin protein and mRNA expression levels were significantly decreased compared with untreated 2K1C rats, but that LV systolic performance was unchanged by either treatment. These data suggest that the cardiac hypertrophy regression induced by the ACEI perindopril is likely mediated, at least in part, through inhibition of the calcineurin signaling pathway.
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PMID:Angiotensin-converting enzyme inhibitor suppresses activation of calcineurin in renovascular hypertensive rats. 1834 31


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