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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report our experience with calcineurin inhibitor (CNI) withdrawal and MMF monotherapy in 50 adult liver transplant (OLT) recipients with CNI-related toxicity. Thirty-four patients had chronic renal dysfunction (CRD) associated with arterial hypertension, 11 had only CRD and other five patients had hypertension. The mean time between OLT and introduction of MMF was 81 months. After the introduction of MMF, CNI was progressively reduced and withdrawn if possible. At the end of the follow up (mean time: 18 months) CNI was withdrawn in 39 patients (78%), and there was a significant decrease from baseline in serum creatinine (1.81-1.49 mg/dL; p < 0.0001), BUN (76.6-52.8 mg/dL; p < 0.0001) and uric acid (9-7.5 mg/dL; p < 0.0001) levels, and an increase in creatinine clearance (44.7-55.1 mL/min; p < 0.0001). Excluding patients who developed graft rejection and two patients who died, CRD improved in 32 of 40 patients (80%), and arterial hypertension improved in 22 of 29 patients (76%). Five patients (10%) developed acute rejection, and one patient (2%) chronic rejection. Twenty-six patients (52%) experienced side-effects, with asthenia, herpes virus infection, and diarrhea being the most common. Only eight patients (16%) required MMF dose reduction. In conclusion, MMF monotherapy late after OLT improves CRD and hypertension in most patients, is safe and well tolerated.
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PMID:Mycophenolate mofetil can be used as monotherapy late after liver transplantation. 1536 20

Peritoneal dialysis (PD) has seldom been reported in patients developing end-stage renal disease (ESRD) after liver transplantation (LTx). Here we present our recent experience with PD in 5 such patients. Of the 5 patients, 3 were men and 2 were women. Average age at initiation of PD was 64.6 years (range: 54 - 72 years). Chronic renal failure (CRF) was diagnosed an average of 3.8 years (range: 1 - 7 years) post transplant and resulted in ESRD an average of 9.2 years (range: 6 - 15 years) after LTx. Calcineurin inhibitor toxicity was the presumed causative factor in all 5 patients, with biopsy confirmation in 2. All of the patients had hypertension at the time of diagnosis of CRF, 2 had coronary artery disease, and 1 developed diabetes mellitus. No patient had ascites before PD initiation. Peritoneal dialysis catheter implantation was uneventful in all patients. Average duration of follow-up was 13.6 months (range: 6 - 29 months). Three episodes of peritonitis occurred in 2 patients (coagulase-negative staphylococcus, Staphylococcus aureus, and Acinetobacter). All episodes of peritonitis responded to standard treatment. Clearance was found to be adequate in all but 1 patient. One patient died 19 months after initiation of PD. At the time of writing, the remaining 4 patients are alive on PD after an average of 12.2 months (range: 6 - 29 months). We conclude that PD is a viable and safe option for managing ESRD that develops after LTx.
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PMID:Peritoneal dialysis in end-stage renal disease after liver transplantation. 1538 4

Cardiac transplantation is a highly effective therapy for selected patients with end-stage cardiac disease. The management of the patient after heart transplant involves three main strategies: optimization of immunosuppressive therapy, prevention of complications resulting from the transplant or the immunosuppressive agents, and treatment of those complications when they arise. For most patients, optimal current immunosuppression in the first year after transplantation consists of combination therapy with a calcineurin inhibitor (eg, cyclosporine or tacrolimus), corticosteroids, and an antimetabolite agent (eg, azathioprine or mycophenolate mofetil). Ideally, the corticosteroid is weaned and discontinued 1 to 2 years following transplantation and the patient is managed chronically with a two-drug immunosuppressive regimen. The major complications that occur following cardiac transplantation include infection, hypertension, diabetes, dyslipidemia, osteoporosis, graft coronary disease, renal insufficiency, and malignancy. Preventive efforts focused on infection, osteoporosis, renal insufficiency, and malignancy include minimization of immunosuppression. Once established, treatment of any of the above conditions generally relies on standard pharmacologic therapies; however, an understanding of potential drug interactions is critical. In addition, although standard nonpharmacologic therapies may be used to treat several of these conditions, one must be cognizant of special issues related to the post-transplant state.
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PMID:Management of the Patient After Heart Transplant. 1549 63

Percutaneous treatment of renal artery stenosis (RAS) is an accepted procedure and numerous reports have been published. However, experience with its use in RAS in the transplanted kidney in children is scarce. Since 1994 we have diagnosed RAS in seven children with the use of Doppler ultrasonography (US), confirming it with percutaneous angiography (PAG). In six of the seven patients percutaneous transluminal angioplasty (PTA) was performed. In one patient a metallic stent was placed due to the extension of the arterial lesion, and a second stent was placed in another child when a re-stenosis was diagnosed 1 month after the PTA. All patients presented with hypertension (de novo or 30% increase over previous values). After ruling out acute rejection, calcineurin inhibitor toxicity, and urinary obstruction, US was performed and, when an increase in arterial flux velocity was registered, PAG was also performed. Six children showed an increase in serum creatinine (Cr) and proteinuria. Blood pressure decreased after the procedure and Cr returned to previous levels in all children. One of the grafts was lost due to chronic transplant rejection 7 years later. The other children have a functioning kidney. Although this is a small group of patients, the consistently good results and the lack of reported experience prompted us to communicate our preliminary observation.
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PMID:Percutaneous treatment of transplant renal artery stenosis in children. 1550 69

The safety and efficacy of tacrolimus (Prograf) in renal transplantation is well established. Achieving longterm patient and graft survival are the ultimate goals following transplantation. Many factors negatively impact long-term transplant outcomes, including graft rejection, renal dysfunction and cardiovascular risk factors (hypertension, hyperlipidaemia, and post-transplant diabetes mellitus (PTDM)). Accordingly, careful consideration of the immunosuppressive strategy and its impact on these factors is critical to optimising outcomes. Clinical trials and registry studies conducted over the past decade have demonstrated tacrolimus to be a cornerstone immunosuppressant in renal transplantation. Compared with cyclosporine treatment, tacrolimus has been shown to be associated with decreased acute and chronic rejection, improved renal function over the long-term post-transplant, and a lower incidence of hyperlipidaemia and hypertension. In early studies, the incidence of PTDM was significantly higher in patients receiving tacrolimus; however, recent large clinical trials have revealed no significant between-group differences in the incidence of PTDM with tacrolimus treatment and cyclosporine microemulsion treatment. Together, these findings may translate into improved long-term transplant outcomes with tacrolimus-based immunosuppression. Although approved only for kidney and liver transplantation in the US, Prograf was the calcineurin inhibitor used in the majority of patients transplanted in 2003: kidney (67%), liver (89%), kidney/pancreas (81%), pancreas (77%), lung (65%), heart/lung (48%), and heart (42%).
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PMID:Tacrolimus based immunosuppression. 1559 82

Sirolimus (rapamycin) is a macrocyclic lactone isolated from a strain of Streptomyces hygroscopicus that inhibits the mammalian target of rapamycin (mTOR)-mediated signal-transduction pathways, resulting in the arrest of cell cycle of various cell types, including T- and B-lymphocytes. Sirolimus has been demonstrated to prolong graft survival in various animal models of transplantation, ranging from rodents to primates for both heterotopic, as well as orthotopic organ grafting, bone marrow transplantation and islet cell grafting. In human clinical renal transplantation, sirolimus in combination with ciclosporin (cyclosporine) efficiently reduces the incidence of acute allograft rejection. Because of the synergistic effect of sirolimus on ciclosporin-induced nephrotoxicity, a prolonged combination of the two drugs inevitably leads to progressive irreversible renal allograft damage. Early elimination of calcineurin inhibitor therapy or complete avoidance of the latter by using sirolimus therapy is the optimal strategy for this drug. Prospective randomised phase II and III clinical studies have confirmed this approach, at least for recipients with a low to moderate immunological risk. For patients with a high immunological risk or recipients exposed to delayed graft function, sirolimus might not constitute the best therapeutic choice--despite its ability to enable calcineurin inhibitor sparing in the latter situation--because of its anti-proliferative effects on recovering renal tubular cells. Whether lower doses of sirolimus or a combination with a reduced dose of tacrolimus would be advantageous in these high risk situations remains to be determined. Clinically relevant adverse effects of sirolimus that require a specific therapeutic response or can potentially influence short- and long-term patient morbidity and mortality as well as graft survival include hypercholesterolaemia, hypertriglyceridaemia, infectious and non-infectious pneumonia, anaemia, lymphocele formation and impaired wound healing. These drug-related adverse effects are important determinants in the choice of a tailor-made immunosuppressive drug regimen that complies with the individual patient risk profile. Equally important in the latter decision is the lack of severe intrinsic nephrotoxicity associated with sirolimus and its advantageous effects on arterial hypertension, post-transplantation diabetes mellitus and esthetic changes induced by calcineurin inhibitors. Mild and transient thrombocytopenia, leukopenia, gastrointestinal adverse effects and mucosal ulcerations are all minor complications of sirolimus therapy that have less impact on the decision for choosing this drug as the basis for tailor-made immunosuppressive therapy. It is clear that sirolimus has gained a proper place in the present-day immunosuppressive armament used in renal transplantation and will contribute to the development of a tailor-made immunosuppressive therapy aimed at fulfilling the requirements outlined by the individual patient profile.
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PMID:Benefit-risk assessment of sirolimus in renal transplantation. 1569 Dec 25

Kidney transplantation is the best treatment for patients with end-stage renal disease, both in terms of survival benefit and quality of life. The major limitation is the continuing shortage of kidneys suitable for transplantation, reinforcing the need to maximise graft survival. After the first year of transplantation, chronic renal allograft dysfunction (CRAD) is the first cause of late graft deterioration and failure. CRAD has been defined as a progressive renal dysfunction, independent of acute rejection, drug toxicity and recurrent or de novo nephropathy, with features on biopsy of chronic allograft nephropathy (CAN) characterised by vascular intimal hyperplasia, tubular atrophy, interstitial fibrosis and chronic transplant glomerulopathy. Protocol biopsy-based studies have demonstrated a high and early prevalence of CAN lesions during the first year in patients with normal and stable renal function. Beyond 1 year, the injuries associated with calcineurin inhibitors (CNIs) appear to be very common. The physiopathology of CRAD is complex and multifactorial. Both alloantigen-dependent factors (acute rejection, HLA matching, donor-specific antibodies, inadequate immunosuppression) and alloantigen-independent factors (donor age, brain death, ischaemia/reperfusion injuries, hypertension, hyperlipidaemia, cytomegalovirus, CNI-related nephrotoxicity) are involved. Consequently, CRAD appears as a dynamic process, evolving with time, and immunosuppressive regimens need to be modulated in order to provide the most suitable treatment at the different phases of its natural history. On the basis of this scheme, the new paradigm would be the use of a CNI-based regimen during the period of maximal risk of (subclinical) acute rejection, followed by a conversion to a CNI-free regimen in order to avoid the long-term consequences of nephrotoxicity. Fortunately, new agents are being introduced in clinical practice providing a large range of combinations and allowing individualisation of immunosuppressive regimens. Large, prospective, multicentre trials are warranted, and the challenge is to define new endpoints of CRAD and to determine the best therapeutic strategy.
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PMID:Combating chronic renal allograft dysfunction : optimal immunosuppressive regimens. 1574 97

Calcineurin inhibitors potentially contribute to risk of cardiovascular events through the development of new-onset diabetes mellitus, hypertension and hyperlipidemia. The exact extent to which calcineurin inhibitors affect these risk factors is difficult to establish since pre-existing renal disease and concomitant immunosuppressive agents (such as steroids or TOR inhibitors) also exert an effect. Clinical trials have consistently shown a higher incidence of new-onset diabetes mellitus with tacrolimus, which has been borne out in large-scale registry analyses. However, the risk of hypertension is approximately 5% higher with cyclosporine than tacrolimus, as is the risk of hyperlipidemia. Statin therapy is effective in treating dyslipidemia and has significant benefits in renal transplant patients. An individualized approach to choice of calcineurin inhibitor, by which cyclosporine or tacrolimus are selected based on the patient's particular risk profile, may thus help to reduce the toll of cardiovascular mortality among renal transplant recipients in the future.
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PMID:Assessing the relative risk of cardiovascular disease among renal transplant patients receiving tacrolimus or cyclosporine. 1577 54

Posttransplant hypertension is a major risk factor for cardiovascular disease and chronic renal allograft dysfunction. A significant number of transplant recipients suffer from posttransplant hypertension in part because of corticosteroid and calcineurin inhibitor use. Although the optimal blood pressure range and the antihypertensive agents of choice in the transplant population have not been determined, the guidelines for blood pressure control in the general population can be extrapolated to the transplant population. The choice of an antihypertensive regimen should be tailored on the basis of the individual patient's risk factors and comorbidities.
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PMID:Management of hypertension in solid-organ transplantation. 1583 66

Side effects of calcineurin inhibitors (CNIs) include nephrotoxicity and hypertension. Moreover, children have a higher risk of infections and posttransplantation lymphoproliferative disorders. We retrospectively evaluated the efficacy and safety of Sirolimus (SRL) in 18 patients, who were 10.52 +/- 5.03 years at time of transplantation and received a CNI as the core immunosuppression. The most common indications for starting SRL therapy were chronic allograft nephropathy, Epstein-Barr virus-associated neoplasia, and thrombotic microangiopathy. The patients were converted to SRL at 49.14 +/- 45.9 months posttransplantation. Mean follow-up after the switch to SRL was 13.83 +/- 7.24 months. All patients who began SRL therapy remained on that medication. We observed a significant improvement (P < .05) in glomerular filtration rate assessed using the Schwartz formula at 3 months, which was sustained thereafter. There were no changes in proteinuria, plasma lipids, and platelet number. Although the prevalence of hypertensive patients decreased during follow-up, it was not significant. There was one steroid-sensitive, acute rejection episode. Serious adverse events included 1 death due to a relapse of B lymphoma, 1 sepsis, and 1 pancreatic pseudo-cyst. Adverse events were present in 17% of patients: 3 Herpes Simplex infections, and 1 dose-related lymphedema. Further studies are necessary to assess the impact of adverse events in the pediatric transplant population receiving SRL as immunosuppression.
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PMID:Sirolimus in pediatric renal transplantation. 1584


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