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)

Microvascular endothelial cells play a key role in transplant immunology. They are also important targets for calcineurin inhibitors. We recently demonstrated elevated numbers of circulating endothelial cells in renal transplant recipients with and without rejection in comparison with healthy controls. Because these patients received either cyclosporine or tacrolimus, we speculated that endothelial damage from calcineurin inhibitors might be responsible for these findings. In the present study, we tested the hypothesis that treatment with calcineurin inhibitors leads to an increase in circulating endothelial cells. We studied 57 renal transplant recipients: 19 on a calcineurin inhibitor-free immunosuppressive regimen and 38 patients on a standard immunosuppressive regimen, including cyclosporine, and matched them for age and serum creatinine. Endothelial cells were isolated from peripheral blood with anti-CD-146-coated immunomagnetic Dynabeads and were counted by fluorescence microscopy. Patients with cyclosporine therapy had elevated numbers of circulating endothelial cells (median 26, range 12 to 82 cells/mL) compared with healthy controls (median 6, range 0 to 82 cells/mL; P<0.001). Patients without calcineurin inhibitor treatment had significantly lower cell numbers (median 12, range 0 to 32 cells/mL; P<0.003) and were not significantly different from normal, untreated controls. In conclusion, renal transplant recipients who do not receive calcineurin inhibitors have significantly lower numbers of circulating endothelial cells than their age- and creatinine-matched counterparts who receive these drugs. We suggest that elevated numbers of circulating endothelial cells indicate damage from calcineurin inhibitors in renal transplant recipients and that circulating endothelial cells are a novel marker of endothelial damage.
Hypertension 2003 Mar
PMID:Circulating endothelial cells are a novel marker of cyclosporine-induced endothelial damage. 1262 86

Isolated visceral angioedema is an extremely rare complication of angiotensin-converting enzyme inhibitors (ACEIs). We report the first known case of ACEI-associated visceral angioedema occurring in a liver transplant recipient who presented with acute-onset abdominal pain, nausea, vomiting, diarrhea, radiologic findings of small bowel edema, and ascites. Heightened awareness of the phenomenon of isolated ACEI-associated visceral angioedema is necessary given the increasing use of these medications for treating hypertension related to calcineurin inhibitors and the need to avoid unnecessary surgical or diagnostic interventions in solid-organ transplant recipients.
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PMID:Angiotensin-converting enzyme inhibitor-induced isolated visceral angioedema in a liver transplant recipient. 1264 Mar 18

Hypertension (HTN) contributes to the high incidence of cardiovascular disease mortality as well as chronic allograft nephropathy (CAN) and late graft failure in renal transplant recipients. The mechanisms are complex and may involve pathogenic factors attributable to the host, allograft, and immunosuppressive drugs. Calcium channel blockers should be used to ameliorate the nephrotoxicity of calcineurin inhibitors in the early years after transplantation. Angiotensin-converting enzyme inhibitors and angiotensin-2 type-1 receptor blockers are safe and effective, have antiproteinuric effects, slow the progression of CAN, and may provide survival benefits. Diuretics and/or beta-adrenergic receptor blockers are frequently added in combination regimen. Appropriate adjustment of the immunosuppressive drugs should also be considered for the long-term care of kidney recipients with HTN.
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PMID:Hypertension after kidney transplantation: impact, pathogenesis and therapy. 1269 25

Sirolimus was used as a single agent for maintenance immunosuppression in a pilot trial of 29 primary kidney transplant patients using lymphocyte depletion with Campath-1H as an induction strategy. This allowed sirolimus to be analyzed (dose, blood level, and side effect profile) in the absence of steroid and calcineurin inhibitors. A sirolimus dose of 4 mg/day resulted in blood levels in the 8 to 9 ng/mL range. Of the 29 patients, 8 patients (28%) had rejection. The sirolimus levels were not significantly different in patients with or without rejection. The cardiovascular risk profile in terms of lipid profile and hypertension control was favorable. Increase in cholesterol and triglyceride levels at one month (not statistically significant) necessitated treatment in 60% of patients with decline in levels by 6 and 12 months. Management of hypertension was also favorable with the majority of patients (55%) being on one hypertensive medication. Sirolimus monotherapy was well tolerated on the whole. Wound healing, leukopenia, and anemia were not significant problems. In conclusion, monotherapy has been well tolerated with a favorable side effect profile. However, a rejection rate of 28% was noted.
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PMID:Sirolimus monotherapy following Campath-1H induction. 1274 84

Since its introduction in renal transplantation in 1999, sirolimus is being used by an increasing number of liver transplant centers. Compared to the calcineurin inhibitors, sirolimus acts through a separate signal transduction pathway and has a myriad of important biologic effects including: inhibition of lymphocyte proliferation, inhibition of fibrosis and fibroblast proliferation, and antineoplastic effects. The clinical side-effect profile of this drug is also different than calcineurin inhibitors. Most important, sirolimus does not cause glucose intolerance, hypertension, or renal insufficiency. As a result, this drug offers significant potential advantages over conventional immunosuppressive agents. However, sirolimus may cause hyperlipidemia and has also been associated with hepatic artery thrombosis in liver transplant recipients. This review will summarize the published data on sirolimus in liver transplantation, focusing on the potential advantages and disadvantage of the use of this drug in liver transplant recipients. Finally, the potential benefits of antifibrosis and antineoplastic effects of sirolimus in liver transplant recipients will be discussed.
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PMID:Sirolimus in liver transplantation. 1274 96

With current immunosuppression elevated blood pressure is found in almost 90% of renal graft recipients. Major causes of this finding are impairment of renal function, secondary to chronic allograft nephropathy or (less frequently) recurrence of primary renal disease, the use of calcineurin inhibitors as immunosuppresants, uncontrolled renin secretion by the shrunken kidneys of the recipient, stenos- ing lesions of the transplant artery (or the upstream arteries of the recipient), polycytemia and (genetic predisposition to) hypertension of the graft donor. Even minor degrees of blood pressure elevation have a significant impact on survival of the recipient and on graft survival, presumably by amplifying vascular injury to the graft. In this respect, elevation of systolic blood pressure and an abnormal circadian blood pressure profile are of particular relevance. In contrast to previous opinion, ACE inhibitors are indicated in the treatment, but, given the causal role of sodium retention in graft vasoconstriction, diuretics and calcium channel blockers remain main stays of antihypertensive treatment in the renal allograft recipient.
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PMID:Hypertension after renal transplantation. 1277 71

Posttransplantation hypertension has been identified as an independent risk factor for chronic allograft dysfunction and loss. Based on available morbidity and mortality data, posttransplantation hypertension must be identified and managed appropriately. During the past decade, calcium channel blockers have been recommended by some as the antihypertensive agents of choice in this population, because it was theorized that their vasodilatory effects would counteract the vasoconstrictive effects of the calcineurin inhibitors. With increasing data becoming available, reexamining the use of traditional antihypertensive agents, including diuretics and beta-blockers, or the newer agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, may be beneficial. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit, from both a renal and a cardiovascular perspective. Beta-blockers, diuretics, and ACE inhibitors have all demonstrated significant benefit on morbidity and mortality in patients with cardiovascular disease. Calcium channel blockers have been shown to possess the ability to counteract cyclosporine-induced nephrotoxicity. When compared with beta-blockers, diuretics, and ACE inhibitors, however, the relative risk of cardiovascular events is increased with calcium channel blockers. With the long-term benefits of calcium channel blockers on the kidney unknown and a negative cardiovascular profile, these agents are best reserved as adjunctive therapy to beta-blockers, diuretics, and ACE inhibitors.
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PMID:Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients: fact or fiction. 1282 Aug 20

It is estimated that there are greater than 100000 kidney transplant recipients with a functioning graft in the United States. Recent advances in immunosuppression have improved short-term graft survival rates and decreased early mortality by decreasing the incidence and therapy for acute rejection episodes. For those accepted on the waiting list, transplant prolongs patient survival compared with remaining on dialysis. During the 1990s, 3 new immunosuppressive drugs were introduced in clinical kidney transplantation. All were approved for use by the Food and Drug Administration after large, controlled, randomized trials. Mycophenolate mofetil (MMF), when combined with cyclosporine (CSA) and prednisone, lowered acute rejection rates by nearly 50% compared with control. Tacrolimus compared with CSA also significantly reduced acute rejection rates in kidney transplant recipients, but was associated with a significant increase in posttransplant diabetes mellitus (PTDM) in the early trials. When evaluated in combination with MMF, the incidence of PTDM was much lower. At the end of the decade, sirolimus was shown in several randomized trials to lower acute rejection rates and is believed to be less nephrotoxic compared with calcineurin inhibitors. All of the randomized trials were not statistically powered to assess long-term superiority. Registry analyses have been performed that appear to show some long-term benefit of immunosuppressive therapy with MMF. Other outcome assessments in kidney transplant recipients include risk factors for chronic allograft nephropathy, hypertension, hyperlipidemia, and bone disease. Although there are few randomized trials, understanding of the significance of these common complications has progressed and strategies for therapy and intervention have been developed. This article focuses on the randomized trials of immunosuppressive therapy and complications associated with use of these drugs. In addition, we review the current management and intervention for the comorbidities associated with the long-term clinical management of the kidney transplant recipient.
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PMID:Outcomes in kidney transplantation. 1283 99

Kidney grafts from suboptimal donors are more likely to suffer the nephrotoxic side-effects of cyclosporine than kidneys from standard donors. In an attempt to avoid the use of cyclosporine, we carried out a prospective study in low-immunological risk recipients of suboptimal kidneys, using an immunosuppressive protocol combining Thymoglobuline in induction with a bi-therapy of mycophenolate mofetil (MMF) and steroids. Patients with panel reactive antibodies (PRA) <50% receiving a first renal transplant from a suboptimal donor (age >or=50, non heart beating, arterial hypertension, or acute renal failure) or a kidney at risk of delayed graft function (DGF) because of a prolonged cold ischaemia time (CIT) of 24 h or more, were eligible for this trial. Between September 1996 and December 1999, 30 patients were enrolled for the trial and treated with MMF 2 g orally, pre-operatively, and 3 g daily, post-operatively; Thymoglobuline 2 mg/kg IV pre-operatively, 1.5 mg/kg IV the next day, and for doses of 1 mg/kg IV given on alternate days; and prednisolone 0.25 mg/kg per day, reduced progressively from the end of the first month to 0.1 mg/kg per day by 3 months post-transplant. Cyclosporine was added only if rejection grade II or higher, or a reduction in MMF below 1 g daily, occurred. Ten patients (30%) suffered from DGF, and one kidney suffered primary non function. Seven patients (24%) suffered acute rejection (six were biopsy proven, 3 grade I and 3 grade II). MMF dosage was reduced in 28 patients because of adverse events, and calcineurin inhibitors were introduced in 16 patients. There were 14 episodes of opportunistic infection (cytomegalovirus (CMV 10), Herpes zoster 2, Listeria monocytogenes 1, Pseudomonas aeuruginosa 1), and 7 malignancies (skin 2, thyroid 1, lung 1, Kaposi's sarcoma 2, post-transplantation lymphoproliferative disorder 1). Mean serum creatinine was 178, 199, 213, and 218 micromol/l at 1, 2, 3 and 5 years after transplantation, respectively. Actuarial patient and graft (after censoring for death) survival was 94% and 83% after 1 year and 79% and 65% after 5 years, respectively. These results show that with the combination of MMF, Thymoglobuline and steroids the use of cyclosporine can be delayed, and in a few cases completely avoided, with good efficacy in terms of prevention of rejection and recovery of renal function. Regardless of acceptable patient and graft survival, side-effects of MMF at the doses used in this protocol were common and led to overimmunosuppression in the long-term. Starting MMF at low dose, MPA monitoring and probably CMV prophylaxis may improve the results of this regimen.
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PMID:Calcineurin inhibitor-free immunosuppression based on antithymocyte globulin and mycophenolate mofetil in cadaveric kidney transplantation: results after 5 years. 1287 30

Recently, new calcineurin inhibitors, such as tacrolimus (FK-506) and microemulsion cyclosporin, have been approved for maintenance immunosuppression in renal transplant recipients and short-term outcomes have been accumulating. In the majority of patients, these calcineurin inhibitors have been used in combination with new immunosuppressive drugs, such as mycophenolate mofetil (MMF) or sirolimus. Under these circumstances, a comparison of cyclosporin and tacrolimus provides the answer to a very important controversial issue. Which drug should we choose in individual patients? In an attempt to answer this question, this review compared the use of tacrolimus and cyclosporin in modern immunosuppressive regimens, which have already been published in well designed clinical studies, and discusses how immunosuppression should be individualised in renal transplant patients.Overall, short-term patient and graft survival with cyclosporin microemulsion and tacrolimus is almost identical. The incidence of acute rejection is generally lower in tacrolimus/azathioprine- than in cyclosporin/azathioprine-treated patients. However, in conjunction with MMF, the difference in the incidence of acute rejection between tacrolimus- and cyclosporin-treated patients became smaller. Adverse events, such as hypertension, hyperlipidaemia and cosmetic changes (gum hypertrophy, hirsutism) seem to be less frequent in tacrolimus-treated than in cyclosporin-treated patients. Recent randomised studies showed that the incidence of post-transplant diabetes mellitus was almost identical between low-dose tacrolimus- and cyclosporin-treated patients. According to the data discussed in this review, the recommendation on the choice of calcineurin inhibitors at this moment is that either cyclosporin or tacrolimus can be used safely and effectively for patients without any risk factors. However, at our centre, we prefer tacrolimus to cyclosporin in patients with a high risk for rejection, such as those with ABO-incompatibility, delayed graft function, sensitisation, and African American race and some other risk factors, such as hypertension and hyperlipidaemia. Moreover, tacrolimus may be preferable to cyclosporin for women because of hirsutism and for children because of the steroid-sparing effect. We consider that cyclosporin should be chosen when patients experience tacrolimus-related adverse events, such as severe chest pain, tremor, gastrointestinal symptoms and encephalopathy. In conclusion, well tolerated and effective immunosuppression is feasible with both cyclosporin and tacrolimus. In the current immunosuppressive regimens, a calcineurin inhibitor, either tacrolimus or cyclosporin, is the essential basic standard immunosuppressant. Clinicians need to decide the best means of optimising therapy for individual patients, based on various risk factors, such as risk of rejection, i.e. sensitisation, delayed graft function and ABO-incompatibility, and some adverse events, such as hypertension, hyperlipidaemia and cosmetic changes.
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PMID:Calcineurin inhibitors in renal transplantation: what is the best option? 1288 61


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