Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early results of an alteration in immunosuppressive protocol of tacrolimus conversion at a mean follow-up of 16 (range 1 to 36) months are presented with a mean time after transplantation of 34 +/- 1.4 months (range 1 to 158 months). Chronic allograft nephropathy in 16 (17%) patients, nephrotoxicity related to cyclosporine in 27(23%) patients and steroids resistant acute rejection in 64 (58%) represented the indications for tacrolimus conversion. Before starting tacrolimus there were 1 acute rejection episode in 37 patients, 2 in 17 patients, and 3 in 10 patients. After the drug conversion, 1 acute rejection occurred in 18 and 2 acute rejection in 4 patients. Graft loss was seen in 16 (16%) patients after drug conversion. Tacrolimus was withdrawn due to diabetes mellitus (n = 9), epilepsy (n = 4), and severe Nocardia sepsis, lymphoma and Kaposi sarcoma (each in one patient). Decreases in serum creatinine and increases in blood glucose levels were significantly associated with the tacrolimus doses (P = 0.0004 and P = 0.0400, respectively). The increase in creatinine clearance values were closely related to higher tacrolimus levels. The target range with maximum efficacy and minimum toxicity seemed to be 10 to 15 ng/mL. Tacrolimus conversion can be successful in cases of rejection and nephrotoxicity, but dose-dependent blood glucose elevations require close observation in these patients.
 ...
PMID:Tacrolimus conversion in kidney transplant recipients: analysis of 107 patients. 1501 27

For many years new-onset diabetes after transplantation has been recognized as a complication of solid-organ transplantation, although its importance has been greatly underestimated. Studies have shown that the cumulative incidence of this condition in heart transplant recipients may reach 32% at 5 years, similar to that reported in kidney and liver transplant patients. Several factors predispose to increased risk for developing new-onset diabetes after transplantation, including age, ethnicity, family history of diabetes, obesity and immunosuppressive therapy. Corticosteroids are associated with the greatest risk of developing the condition. Tacrolimus is more diabetogenic than cyclosporine in kidney and liver transplant patients, but there are few data reporting the effects of these agents in heart transplant patients. In kidney transplant patients, diabetes is known to be a significant risk factor for cardiovascular disease post-transplant. Although this has yet to be demonstrated clearly in heart transplant patients, evidence suggests that new-onset diabetes after transplantation may play a role in the development of cardiac allograft vasculopathy (CAV). Because CAV is the major limitation to long-term survival in this population, it is clear that efforts should be made to reduce the risk of diabetes and treat this condition appropriately. Management of transplant recipients with new-onset diabetes after transplantation has been assisted by the recent publication of International Consensus Guidelines. The guidelines were developed to establish a standard definition and describe risk factors for new-onset diabetes after transplantation. Use of these guidelines will help to prospectively identify those at risk of developing new-onset diabetes after transplantation so that therapeutic strategies can be individualized early in the treatment regimen. These management approaches should help to lower the risk of new-onset diabetes after heart transplantation and reduce the possible long-term consequences of the condition.
 ...
PMID:New-onset diabetes after transplantation. 1509 5

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

Cyclosporine and tacrolimus, two calcineurin inhibitors, show different side effects and toxicities. The data concerning their nephrotoxicity are few and conflicting. A retrospective study was performed in 2 groups of renal transplant recipients treated with cyclosporine or tacrolimus to evaluate graft function and side effects. All patients had completed at least 6 months of follow-up before inclusion in the study. Group I included 10 patients who were converted from cyclosporine to tacrolimus, due to cosmetic problems or due to chronic graft dysfunction with creatinine values <3 mg/dL. After conversion, there was a significant reduction in creatinine values (from 2.43 +/- 1.21 to 1.86 +/- 0.72 mg/dL; P =.023) and an improvement in creatinine clearance (from 47.5 +/- 19.2 to 56.1 +/- 18.9 mL/min; P =.047). The lipid profile did not change, but there was a trend to better blood pressure control with less antihypertensive drugs. Group II compared 2 subgroups of patients receiving kidneys from the same donor, one treated with cyclosporine and the other with tacrolimus. Tacrolimus patients showed better renal function; namely, creatinine was 1.15 +/- 0.27 versus 1.44 +/- 0.33 mg/dL (P =.029) and creatinine clearance was 87.7 +/- 27.1 versus 60.3 +/- 25.9 mL/min (P =.043). Lipid and blood pressure values were not different between the 2 subgroups, but tacrolimus patients tended to need a lower number of antihypertensive medications. The incidence of de novo diabetes mellitus was approximately 20% among patients using tacrolimus. We concluded that tacrolimus may be less nephrotoxic than cyclosporine. Tacrolimus patients showed better graft function and easier blood pressure control, but a high incidence of posttransplantation diabetes mellitus.
 ...
PMID:Cyclosporine versus tacrolimus in kidney transplantation: are there differences in nephrotoxicity? 1519

In the control of acute rejection, attention is being focused more and more on the long-term adverse effects of the immunosuppressive agents used. Since cardiovascular disease is the main cause of death in renal transplant recipients, optimal control of cardiovascular risk factors is essential in the long-term management of these patients. Unfortunately, several commonly used immunosuppressive drugs interfere with the cardiovascular system. In this review, the cardiovascular adverse effects of the immunosuppressive agents currently used for maintenance immunosuppression are thoroughly discussed. Optimising immunosuppression means finding a balance between efficacy and safety. Corticosteroids induce endothelial dysfunction, hypertension, hyperlipidaemia and diabetes mellitus, and impair fibrinolysis. The use of corticosteroids in transplant recipients is undesirable, not only because of their cardiovascular effects, but also because they induce such adverse effects as osteoporosis, obesity, and atrophy of the skin and vessel wall. Calcineurin inhibitors are the most powerful agents for maintenance immunosuppression. The calcineurin inhibitor ciclosporin (cyclosporine) not only induces these same adverse effects as corticosteroids but is also nephrotoxic. Tacrolimus has a more favourable cardiovascular risk profile than ciclosporin and is also less nephrotoxic. It has little or no effect on blood pressure and serum lipids; however, its diabetogenic effect is more prominent in the period immediately following transplantation, although at maintenance dosages, the diabetogenic effect appears to be comparable to that of ciclosporin. The diabetogenic effect of tacrolimus can be managed by reducing the dose of tacrolimus and early corticosteroid withdrawal. The effect of tacrolimus on endothelial function has not been completely elucidated. The proliferation inhibitors azathioprine and mycophenolate mofetil (MMF) have little effect on the cardiovascular system. Yet, indirectly, by inducing anaemia, they may lead to left ventricular hypertrophy. MMF is an attractive alternative to azathioprine because of its higher potency and possibly lower risk of malignancies. Sirolimus also induces anaemia, but may be promising because of its antiproliferative features. Whether the hyperlipidaemia induced by sirolimus counteracts its beneficial effects is, as yet, unknown. It may be combined with MMF, however, initial attempts resulted in severe mouth ulcers.
 ...
PMID:Effect of immunosuppressive agents on long-term survival of renal transplant recipients: focus on the cardiovascular risk. 1534 97

Evidence suggests that steroid sparing in renal transplantation is associated with good outcomes, although there are limited data regarding steroid sparing in Tacrolimus and Mycophenolate Mofetil (MMF)-based regimes. In this study we describe the use of these agents in 101 consecutive patients undergoing renal transplantation using only a 7-day course of prednisolone. Median follow-up was 33 months (range 18-44). Patient and graft survival at 1 year were 100% and 98%, respectively. The acute rejection rate at both 6 and 12 months was 19%, with two episodes beyond 12 months. Anti-CD25 monoclonal antibody (anti-CD25 mAb) was administered to 25 patients at high immunological risk: a trend toward a lower rejection rate was seen in these patients compared with those at lower risk but not receiving induction therapy (8% vs. 22%; p = 0.11). Two patients experienced recurrent rejection. Of the twenty-three rejection episodes in total, 26% showed vascular involvement. Allograft function was preserved at 12 months with a mean creatinine of 144 micromol/L and mean estimated glomerular filtration rate (GFR) of 55 mL/min. At 12 months, the incidence of post-transplant diabetes mellitus was 3.5%. This steroid-sparing regime is associated with excellent patient and graft outcomes, and a low incidence of side effects.
 ...
PMID:Steroid sparing with tacrolimus and mycophenolate mofetil in renal transplantation. 1547 85

Both tacrolimus and mycophenolate mofetil (MMF) are potent immunosuppressive agents used in combination for prevention of acute rejection in renal transplantation. We studied the efficacy and safety of tacrolimus/MMF-based primary immunosuppression as well as their pharmacokinetics (PK) in Chinese renal transplant recipients. Oral tacrolimus was initiated at about 0.2 mg/kg/d, dose which was adjusted to achieve target trough levels of 10 to 20 ng/mL at 3 months and 5 to 10 ng/mL thereafter. The patients also received MMF (0.5 g bid) and prednisolone. PK profiles were studied at 1 week, and 1, 3, and 6 months posttransplant. Blood samples were taken at 0 (predose), 20, 40, 60, 75, and 90 minutes and 2, 4, 6, 8, 10, and 12 hours postdose for each profile. Plasma MPA and whole blood tacrolimus levels were determined by HPLC and EMIT methods respectively. Eight patients were studied with mean follow-up of 16.1 +/- 2.4 months. One patient (12.5%) experienced a borderline acute rejection episode. Both 1-year graft and patient survival rates were 100%. Posttransplant diabetes, diarrhea, and hand tremor occurred in 12.5%, 12.5%, and 37.5%, respectively. No patient had an opportunistic infection. Tacrolimus trough concentrations showed a fair correlation with AUC(0-12h) (R(2) = 0.587). Mean MPA AUC values at 1, 3, and 6 months were 40.5 +/- 9.4, 44.4 +/- 17.3, and 57.2 +/- 20.7 mug*h/mL, respectively (P = .0486, n = 7). In conclusion, primary immunosuppression with tacrolimus, low-dose MMF (0.5 g bid), and prednisolone is effective and safe with adequate systemic MPA exposure in renal transplant recipients.
 ...
PMID:Primary immunosuppression with tacrolimus and low-dose mycophenolate mofetil in renal transplant recipients. 1551 54

The introduction of new immunosuppressants has prompted trials of steroid withdrawal. However, several groups have reported a higher incidence of rejection. We conducted a randomized two-arm, parallel-group, open-label, prospective study to compare steroid withdrawal (at 6 months posttransplant) from the regimens of tacrolimus + mycophenolate mofetil (MMF) (FK group) versus cyclosporine + MMF (CSA group). The entry criteria were recipients of first living donor transplants with no diabetes mellitus (DM), congestive heart failure, chronic liver disease, or acute rejection within 6 months posttransplant. The primary endpoint was a biopsy-proven acute rejection episode or treatment failure within 1 year posttransplant. While 87 recipients were assigned to FK (n = 43) and CSA groups (n = 44) before transplantation, 76 recipients (FK 39, CSA 37) could be tapered off steroids at 6 months posttransplant, since 11 were excluded due to acute rejection within 6 months posttransplant (FK two, CSA three) or protocol violations (FK two, CSA four). After steroid withdrawal, the incidence of acute rejection episodes was 0% in the FK group and 13.5% in the CSA group (P < .05). Other results at 12 months posttransplantation were comparable: the incidences of DM 7.8% versus 0% (FK group vs CSA group), hypercholesterolemia 41.0% versus 59.5%, hypertensives 48.7% versus 59.6% as well as the levels of plasma creatinine 1.21 +/- 0.24 versus 1.31 +/- 0.50 mg/dL (P > .05 in every variable). These data suggest that steroid withdrawal is successful in first living donor renal transplant recipients. Tacrolimus may be significantly more effective than cyclosporine to prevent acute rejection after steroid withdrawal.
 ...
PMID:Randomized trial of tacrolimus versus cyclosporine in steroid withdrawal in living donor renal transplant recipients. 1551 59

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%).
 ...
PMID:Tacrolimus based immunosuppression. 1559 82

Tacrolimus-based immunosuppression is currently accepted as mainstream therapy in many transplant centers worldwide due to its potent immunosuppressive activity compared to cyclosporine. A tacrolimus-based regimen has been successfully used for our living donor liver transplantation (LDLT) recipients. Adverse effects such as neurotoxicity, nephrotoxicity, and new-onset diabetes mellitus, however, have limited its clinical application. In deceased donor liver transplantation, cyclosporine rescue therapy is valuable for such complications, but few reports have described a strategy for conversion in LDLT. Herein, we present our experience of conversion from tacrolimus to cyclosporine therapy in adult LDLT recipients. Among 203 recipients, 37 patients (18%) required conversion, primarily for neurotoxicity (41%), diabetes mellitus (16%), hematopoietic disorder (16%), and gastrointestinal intolerance (11%). Primary adverse events resolved within 2 months after conversion in 35/37 (94%) of the patients. For LDLT recipients unable to maintain effective immunosuppression with tacrolimus, conversion to cyclosporine is an effective option.
 ...
PMID:Conversion to cyclosporine provides valuable rescue therapy for living donor adult liver transplant patients intolerant to tacrolimus: A single-center experience at the University of Tokyo. 1568 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>