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

An eight-yr-old combined liver and kidney transplant recipient for hyperoxaluria type I developed significant proteinuria and hypertension after conversion of a Tacrolimus, MMF, and corticosteroids-based immunosuppression to Sirolimus, low-dose Tacrolimus, and corticosteroids six and a half yr after the transplant for chronic allograft nephropathy. There was only one class I HLA match and the recipient had multiple blood exposures prior to transplantation. The patient was treated with combined hemodialysis and peritoneal dialysis while awaiting transplantation to reduce the oxalate load. A renal biopsy revealed a de novo transplant glomerulopathy that was associated with specific HLA antibodies unrelated to the donor (HLA DR 17 and 18). After reintroduction of MMF, these antibodies became undetectable and the proteinuria completely resolved. We hypothesize that HLA antibodies may cause transplant glomerulopathy even if they are not donor-specific. Their production appears more susceptible to MMF therapy. A thorough work-up of new-onset proteinuria after conversion to Sirolimus should be performed, including an immunological work-up and a renal biopsy.
 ...
PMID:Sirolimus is not always responsible for new-onset proteinuria after conversion for chronic allograft nephropathy. 1743 Apr 94

Erectile dysfunction is common in male kidney transplant recipients. Interference with the physiology of erections can be attributed to recipient co-morbidities, the renal transplant operation, medication adverse effects, relationship problems and changes in mental health. A treatment-oriented evaluation of erectile dysfunction allows the development of treatment plans that are patient-specific. Hypo-gonadal men whose hormone parameters do not improve after renal transplantation may respond to testosterone replacement therapy. Use of recommended doses of the phosphodiesterase-5 inhibitor sildenafil does not significantly modify trough concentrations of the calcineurin inhibitors ciclosporin and tacrolimus or result in impaired renal allograft function. Tacrolimus has been shown to increase the peak concentration and prolong the elimination half-life of sildenafil in kidney transplant recipients. Daily administration of sildenafil has resulted in decreased blood pressure in kidney transplant recipients with treated hypertension and tacrolimus immunosuppression. Intracavernosal injections of alprostadil, with or without papaverine and phentolamine, are effective treatments for erectile dysfunction after renal transplantation and have not resulted in alterations of ciclosporin concentrations or in deterioration of renal function. Penile prostheses can be successfully implanted after pelvic organ transplantation without significant risk of infection.
 ...
PMID:Treating erectile dysfunction in renal transplant recipients. 1748 43

Arterial hypertension develops in up to 80% of renal transplant recipients. Uncontrolled hypertension induces left ventricular hypertrophy, heart failure and death, but also promotes deterioration of allograft function. Cadaveric transplantation, delayed graft function, renal artery stenosis, presence of native kidneys, increased body weight and therapy with calcineurin inhibitors and steroids have been associated with an increased incidence of hypertension after kidney transplantation. Cyclosporine increases both systemic and renal vascular resistance, enhances sympathetic activation, endothelin production and, possibly, decreases vascular relaxation by decreasing the generation of nitric oxide. Tacrolimus has less pronounced prohypertensive role after renal transplantation. Corticosteroids contribute to the development of hypertension, since their withdrawal results in a significant decrease of blood pressure in the majority of patients. Renal artery stenosis occurs in almost 12% of hypertensive renal transplant recipients. It is a correctable cause of hypertension, and for this reason should be investigated in all suspected patients. Doppler ultrasonography is used as the screening method that is highly sensitive and specific in the hands of a well-experienced investigator. However, dependence of the method on the experience of the investigator is its major drawback. Magnetic resonance angiography and spinal computed tomography angiography are useful noninvasive methods, but arteriography remains a method for establishing the definitive diagnosis. Percutaneous balloon angioplasty, with or without placement of the stent, is successful in the majority of patients, but with a high incidence of restenoses (20%). Surgery is indicated for stenoses that cannot be treated with angioplasty or that recur. Auto-transplantation of the kidney with complex stenoses of graft arteries is useful in selected cases. Posttransplant hypertension should be aggressively treated to prevent the development of end-organ damage. Every effort should be invested in reducing immunosuppression when appropriate, together with salt restriction and weight reduction. Calcium channel blockers have good antihypertensive properties accompanied with minimization of cyclosporine-induced renal vasoconstriction. Angiotensin-converting enzyme inhibitors (ACEi) should be used in patients with proteinuria. Renal function should be carefully monitored after their introduction since they may cause transitory deterioration of glomerular filtration and/or hyperkaliemia. ACEi can induce anemia in renal transplant recipients, side effect that is often used in the treatment of posttransplant erythrocytosis. All other antihypertensive drugs could be used, with minoxidil being the most potent one. Patients with resistant hypertension should be investigated for the presence of renal artery stenosis. After exclusion of rejection, renal artery stenosis and recurrent disease, in cases of severe hypertension, native kidneys laparoscopic nephrectomy should be considered.
 ...
PMID:[Arterial hypertension in renal transplant recipients]. 1836 9

Tacrolimus extended-release (XL) is a once-daily formulation recently developed to reduce the frequency of dosing for patients currently using the twice-a-day formulation of tacrolimus (TAC). As reported previously, 67 kidney transplant recipients were safely converted (1:1 mg basis, total daily dose) from TAC twice-a-day to XL once-daily in the morning and were maintained on an am dosing regimen of XL using the same therapeutic monitoring and patient care techniques currently employed with TAC. The 2-year postconversion patient (100%) and graft (98.5%) survival, incidence of biopsy-confirmed acute rejection (6.0%), incidence of multiple rejections (1.5%), and safety profile (posttransplant diabetes, hyperlipidemia, hypertension, infections, renal dysfunction, hepatic dysfunction, and malignancies) were consistent with or more favorable than those previously reported for TAC twice-a-day.
 ...
PMID:Two years postconversion from a prograf-based regimen to a once-daily tacrolimus extended-release formulation in stable kidney transplant recipients. 1758 51

Immune mechanisms play a central role in various diseases such as eczema and psoriasis, and in the past treatment tended to involve corticosteroids and cytostatic drugs. Organ transplantation has stimulated the development of newer immunosuppressants, some of which have also been found to be efficacious in the inflammatory dermatoses. The best studied such immunosuppressant is cyclosporin, which has shown efficacy especially in psoriasis and atopic dermatitis. The major limiting factor in the use of cyclosporin is its adverse effects, especially nephrotoxicity and hypertension. Therefore the risk : benefit ratio should always be considered before initiation of cyclosporin therapy, and the patient should be carefully followed for such adverse effects. Tacrolimus seems to share the efficacy and most of the adverse effects of cyclosporin when used systemically, presumably because of its similar intracellular mechanism of action. Unlike cyclosporin, tacrolimus is efficacious topically, which may allow lower systemic adverse effects to be combined with higher local efficacy. Other newer immunosuppressants include sirolimus (rapamycin) and monoclonal antibodies. Their use in dermatology is still in the research phase, and no conclusions about their clinical potential can yet be made.
 ...
PMID:Use of the newer immunosuppressive agents in dermatology. 1802 Apr 98

Transplantation of haemopoietic stem cells containing immunocompetent cells invariably leads to the development of graft versus host disease (GVHD) in the recipients unless immunosuppressive prophylaxis is administered for approximately 6 months. Despite the availability of immunosuppressive drugs such as cyclosporin, GVHD remains the most important cause of morbidity and mortality in haemopoietic stem recipients. Tacrolimus (FK506), a macrolide lactone isolated from the fermentation broth of Streptomyces tsukubiensis, has been introduced as an agent with greater activity than cyclosporin for GVHD prophylaxis. Several pilot studies using tacrolimus for prophylaxis of acute GVHD have shown promising results leading to 3 major pivotal trials. These studies were nonblinded randomised trials comparing the combination of tacrolimus and methotrexate with cyclosporin and methotrexate in both matched sibling and unrelated donor transplants for the prevention of acute GVHD. All 3 trials showed a significantly lower incidence of acute GVHD in the tacrolimus arm when compared to the cyclosporin arm. The overall and disease-free survival of patients with non-advanced malignancies was similar between the 2 groups. In one matched sibling study, the overall and disease-free survival in high-risk advanced disease patients who received tacrolimus was poorer than in the cyclosporin recipients. However, a recent matched case controlled study using the International Bone Marrow Transplant Registry database confirmed that the poorer survival outcome of the tacrolimus recipients was due to adverse influence of baseline prognostic factors in the tacrolimus group. The toxicity profile of tacrolimus is similar to that of cyclosporin with the exception that the incidence of hirsutism and hypertension is less frequent in tacrolimus recipients. The nephrotoxicity associated with tacrolimus is dose related. Logistic regression analysis indicated that whole blood tacrolimus concentrations greater than 20 ng/ml were associated with significant nephrotoxicity. The current recommended therapeutic concentration range in whole blood is 10 to 20 ng/ml. Some studies found equal efficacy with a therapeutic range of 5 to 15 ng/ml. This review addresses many details on the practical management of adverse effects, dosage and drug interactions.
 ...
PMID:Optimum use of tacrolimus in the prophylaxis of graft versus host disease. 1803 Nov 44

Our objective was to study the complications of chronic renal failure (CRF) among pediatric live-donor kidney transplant recipients. Between March 1976 and December 2005, 1,785 live-donor kidney transplantations were carried out at our center. Of the recipients, 292 were 20 years old or younger (mean age 12.8 years, ranging from 4 years to 20 years). Clinical and laboratory parameters of these 292 patients were analyzed retrospectively. They were 182 boys and 110 girls. Patients who had received transplants before 1988 were treated with prednisolone and azathioprine as combined therapy. From 1988 to 1998, a triple regimen comprising prednisolone, azathioprine and cyclosporine A (CsA) was administered. Tacrolimus and mycophenolate mofetil (MMF) were introduced as primary therapy in 1998. Growth, anemia, infections, and surgical, cardiac, neurologic, bone and other medical complications were assessed. Triple-drug immunosuppression (prednisone + CsA + azathioprine) was used in 68.2% of transplants. Acute rejection rate was 47.6%; chronic rejection rate was 31%. Hypertension (62%) was the commonest complication. Anemia was diagnosed in 61%. A substantial proportion of patients (48%) were short, with height standard deviation scores (SDSs) of less than -1.88. The overall infection rate was high, and the majority (54%) was bacterial. Malignancy was diagnosed in eight (3%) patients. The incidence of urological complications was 14%, and that of vascular complications was 1%. Cardiac complications included left ventricular hypertrophy (LVH) in 47.9% of patients, left atrial enlargement (31.5%) and left ventricular dilatation and systolic dysfunction (13.7% for each). Neuropathic changes were found in 19% of our cases, with the distal muscles of lower limbs more affected. Other complications included avascular bone necrosis in 8% (all of them in the hip joint) and bone loss in 60% of patients. We concluded that, despite the long-term success of pediatric renal transplantation in a developing country, there is a risk of significant morbidity.
 ...
PMID:Complications of pediatric live-donor kidney transplantation: a single center's experience in Egypt. 1807 59

The literature contains very little documentation on neurologic complications in liver transplant recipients for Wilson's disease. We retrospectively reviewed 17 consecutive cases of pediatric liver transplantation for the hepatic form of Wilson's disease to assess the types of neurologic complications that occurred, the incidence of those problems, and associated factors in this patient group. The patients were 12 boys and 5 girls; indications for liver transplantation were fulminant hepatic failure in 3 patients and chronic hepatic failure in 14 patients. Neurologic complications were observed in 10 of the 17 patients as 16 episodes. The most common neurologic complications were seizure (7 episodes in 6 patients) and sudden-onset headache (5 episodes in 4 patients). Tacrolimus was identified as the only possible cause of headache in 3 episodes. Encephalitis was the cause in 1 and intracranial hemorrhage was the cause in the other headache episode. We also noted 1 episode of tremor, 1 episode of acute dystonic reaction, 1 episode of diffuse encephalopathy, and 1 episode of common peroneal nerve palsy. Immunosuppressive agents were the primary cause of 12 of the 16 episodes of neurologic complications. Uremia with hypertension, compression of the right common peroneal nerve, encephalitis, and intracranial hemorrhages attributable to coagulopathy caused 1 neurologic episode each. Neurologic complications in patients with the hepatic form of Wilson's disease were frequent during the first 30 days after pediatric liver transplantation but did not affect survival. Transplantation teams should be aware of the high incidence of neurologic complications in pediatric patients with the hepatic form of Wilson's disease.
 ...
PMID:Neurologic complications of liver transplantation in pediatric patients with the hepatic form of Wilson's disease. 1807 18

Tacrolimus (FK506) is a potent immunosuppressant widely used for organ transplantation patients while diltiazem (DTZ), a calcium-channel inhibitor, is often used in renal transplantation patients to prevent post-transplant hypertension. However, DTZ has a significant pharmacokinetic interaction with FK506. In this study, a rapid and sensitive ammonium-adduct based liquid chromatography-tandem mass spectrometry (LC/MS/MS) method has been developed and validated for the simultaneous determination of FK506 and DTZ in human whole blood using ascomycin as the internal standard (IS). After extraction of the whole blood samples by ethyl acetate, FK506, DTZ and the IS were subjected to LC/MS/MS analysis using electro-spray positive-ion mode ionization (ESI(+)). Chromatographic separation was performed on a Hypersil BDS C18 column (50 mm x 2.1 mm, i.d., 3 microm). The MS/MS detection was conducted by monitoring the fragmentation of 821.7-->768.9 (m/z) for FK506, 415.5-->310.3 (m/z) for DTZ and 809.8-->757.0 (m/z) for IS. The method had a chromatographic running time of approximately 2 min and linear calibration curves over the concentrations of 0.5-200 ng/mL for FK506 and 2-250 ng/mL for DTZ. The recoveries of liquid-liquid extraction method were 58.3-62.6% for FK506 and 50.4-58.8% for DTZ. The lower limit of quantification (LLOQ) of the analytical method was 0.5 ng/mL for FK506 and 2 ng/mL for DTZ. The intra- and inter-day precision was less than 15% for all quality control samples at concentrations of 2, 10, and 50 ng/mL for FK506 and 5, 25, and 100 ng/mL for DTZ. The validated LC/MS/MS method has been successfully used to analyze the concentrations of FK506 and DTZ in whole blood samples from pharmacokinetic studies in renal transplanted patients.
 ...
PMID:Rapid and simultaneous determination of tacrolimus (FK506) and diltiazem in human whole blood by liquid chromatography-tandem mass spectrometry: application to a clinical drug-drug interaction study. 1841 31

Corticosteroids are a cornerstone of immunosuppressive therapy in renal transplantation despite their side effects and morbidity. Newer immunosuppressive agents may be more effective to allow corticosteroid sparing. An interim analysis of 60 completed out of 100 planned primary kidney transplant recipients is presented. All patients on tacrolimus (Prograf) and MMF (Cellcept) were randomized into two groups following a 1:1 distribution for early steroid reduction at posttransplant day 7 (G1; n = 31) versus to long-term maintenance steroids (G2; n = 29). Primary efficacy endpoints were composite endpoint of death, graft loss, or severe acute rejection at 6 and 12 months follow-up. Safety evaluation included severity and frequency of diabetes mellitus, hypertension, hyperlipidemia, leukopenia, infection, malignancy, and severe adverse events. Mean age was 39.1 years, with 45.0% males and 66.7% Caucasians. African-Americans were 25.8% in G1 and 27.6% in G2. One death occurred in each group, as well as one case of severe (Banff III) rejection in G1 (P = 1.00). The incidence of rejection episodes between groups was not significant, namely, 41.9% in G1 and 20.7% in G2 (P = .077). There were no differences between groups concerning mean, systolic and diastolic blood pressure, HbA1c, or creatinine at 12 months. This interim analysis showed no evidence of an increased risk of poorer performance among the early steroid reduction or safety differences in kidney transplant recipients versus a regular dosage steroid group of patients. Further analysis of the complete study data is underway.
 ...
PMID:Corticosteroid reduction with tacrolimus (CORRETA) TRIAL: a prospective Brazilian multicenter, randomized trial of early corticosteroid reduction versus regular corticosteroid dosage maintenance on a tacrolimus (Prograf) and mycophenolate mofetil (Cellcept) immunosuppression regimen in kidney transplant recipients: interim analysis. 1845 88


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