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Transplant Patients (transplant + patient)
Kinds of Transplant Patients Selected AbstractsAnnular Bullae in a Transplant PatientPEDIATRIC DERMATOLOGY, Issue 2 2010Kristen Holland M.D. No abstract is available for this article. [source] Safety and Long-Term Efficacy of Eculizumab in a Renal Transplant Patient with Recurrent Atypical Hemolytic,Uremic SyndromeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009V. Chatelet No abstract is available for this article. [source] The Pathophysiology of Chronic Graft Failure in the Cardiac Transplant PatientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009U. A. Khan Following cardiac transplantation, many patients develop chronic deterioration of graft function, which may lead to a clinical syndrome similar to native chronic heart failure (CHF). This condition of chronic cardiac graft failure (CGF) may also share pathophysiological processes comparable with that of CHF. However, the unique environment following cardiac transplantation may also contribute with a variety of unique mechanisms, deserved of special attention. This review article discusses the complex pathophysiology of CGF after cardiac transplantation, an important yet neglected condition of transplant medicine. [source] Long-term Management of the Liver Transplant Patient: Recommendations for the Primary Care DoctorAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009B. M. McGuire No official document has been published for primary care physicians regarding the management of liver transplant patients. With no official source of reference, primary care physicians often question their care of these patients. The following guidelines have been approved by the American Society of Transplantation and represent the position of the association. The data presented are based on formal review and analysis of published literature in the field and the clinical experience of the authors. These guidelines address drug interactions and side effects of immunosuppressive agents, allograft dysfunction, renal dysfunction, metabolic disorders, preventive medicine, malignancies, disability and productivity in the workforce, issues specific to pregnancy and sexual function, and pediatric patient concerns. These guidelines are intended to provide a bridge between transplant centers and primary care physicians in the long-term management of the liver transplant patient. [source] Aggressive Cutaneous Squamous Cell Carcinoma Associated with Prolonged Voriconazole Therapy in a Renal Transplant PatientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2008A. Vanacker A 69-year-old man, with a history of end-stage renal disease due to polyarteritis nodosa, followed by invasive pulmonary aspergillosis secondary to cyclophosphamide and corticosteroids, received a renal transplant 2 years ago under prophylactic treatment with voriconazole. Because of the severity of the aspergillosis, it was decided to continue voriconazole for a prolonged period. Eighteen months after transplantation, the patient developed a severe facial phototoxic reaction. A few months later, he developed multiple actinic keratoses and a large, rapidly expanding, poorly differentiated squamous cell carcinoma (SCC) with perineural invasion and metastatic lymph nodes, necessitating radical surgery and radiotherapy. Voriconazole therapy has been suggested to be involved in the development of multi-focal invasive SCC when complicated by a phototoxic reaction. Therefore, an alternative antifungal prophylaxis regimen (for instance with posaconazole) should be considered when evaluating patients for solid organ transplantation who are at high risk for the development of cutaneous malignancies. [source] Positron-emission Tomography Used to Diagnose Tuberculosis in a Renal Transplant PatientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2002Neville Kukreja We describe the case of a 22-year-old Portuguese renal transplant patient whose post-transplant course was complicated by prolonged delayed graft function and pyrexia of unknown origin. Conventional imaging techniques were not definitive, but positron-emission tomography (PET) scanning identified abnormalities in the lung and mediastinum that led to a diagnostic biopsy demonstrating mycobacterial infection. [source] Combined Vitamin C and E Supplementation Retards Early Progression of Arteriosclerosis in Heart Transplant PatientsNUTRITION REVIEWS, Issue 11 2002Article first published online: 16 SEP 200 The development of arteriosclerosis is the limiting factor for the long-term survival and the major cause of mortality in patients with heart transplants. Various factors, including oxidative stress, contribute to the progression of the disease. In a recent clinical trial using the intravascular ultrasound technique, which detects the early stages of disease development, supplementation with vitamins C and E retarded the progression of coronary arteriosclerosis during the early stage following cardiac transplantation. [source] Immunotherapy for Invasive Fungal Infections in Transplant Patients: Back to the Future?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010Hans H. Hirsch For kidney transplant patients with life-threatening disseminated fungal infections and failure of modern antifungal therapies, exogenous interferon-gamma might represent an adjunct salvage therapy, but the risk-benefit ratio is not yet established. See Article by Armstrong-James et al on page 1796. [source] Exogenous Interferon-, Immunotherapy for Invasive Fungal Infections in Kidney Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010D. Armstrong-James The incidence of invasive fungal infections (IFIs) in nonneutropenic solid organ transplant patients is increasing. We report our clinical experience with the use of interferon-, (IFN-,) immunotherapy in seven renal transplant patients who developed life threatening, disseminated IFIs refractory to conventional antifungal drug therapy. The infections were all microbiologically and histologically proven. The rapid cure of these disseminated infections with exogenous IFN-, injections was not associated with impaired kidney allograft function despite the use of liposomal amphotericin B in all cases. No clinical toxicity from the IFN-, immunotherapy was seen and no IFI relapsed during long-term follow-up. Our experience is both uncontrolled and in patients with unpredictable fungal infection-related outcomes. However, compared to standard approaches, the accelerated cure of life threatening, disseminated IFIs with 6 weeks of combination antifungal drug therapy and IFN-, immunotherapy saved lives, retained allograft function and led to substantial cost savings in this small patient group. [source] Is Rituximab Safe to Use in Kidney Transplant Patients?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010G. Tydén No abstract is available for this article. [source] The Importance of Skin Cancer Prevention in Organ Transplant Patients An Editorial to Paper by Salgo: ,Switch to Sirolimus in Long-Term Renal Transplant Recipients: Reduced Premalignancies and Nonmelanoma Skin Cancer in a Controlled, Prospective, Randomized, Blinded Study'AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010C. Mitchell Renal transplant patients should be managed by dermatologists to prevent and manage skin cancer, a common cause of morbidity and mortality in organ transplant patients. See article by Salgo et al on page 1385. [source] Risk of Colorectal Carcinoma in Post-Liver Transplant Patients: A Systematic Review and Meta-analysisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010J. Sint Nicolaas Liver transplant patients (LTx) have an increased risk for developing de novo malignancies, but for colorectal cancer (CRC) this risk is less clear. We aimed to determine whether the CRC risk post-LTx was increased. A systematic search was performed in MEDLINE and Cochrane databases to identify studies published between 1986 and 2008 reporting on the risk of CRC post-LTx. The outcomes were (1) CRC incidence rate (IR per 100 000 person-years (PY)) compared to a weighted age-matched control population using SEER and (2) relative risk (RR) for CRC compared to the general population. If no RR data were available, the RR was estimated using SEER. Twenty-nine studies were included. The overall post-LTx IR was 119 (95% CI 88,161) per 100 000 PY. The overall RR was 2.6 (95% CI 1.7,4.1). The non-primary sclerosing cholangitis (PSC) IR was 129 per 100 000 PY (95% CI 81,207). Compared to SEER (71 per 100 000 PY), the non-PSC RR was 1.8 (95% CI 1.1,2.9). In conclusion, the overall transplants and the subgroup non-PSC transplants have an increased CRC risk compared to the general population. However, in contrast to PSC, non-PSC transplants do not need an intensified screening strategy compared to the general population until a prospective study further defines recommendations. [source] Access and Outcomes Among Minority Transplant Patients, 1999,2008, with a Focus on Determinants of Kidney Graft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4p2 2010P.-Y. Fan Coincident with an increasing national interest in equitable health care, a number of studies have described disparities in access to solid organ transplantation for minority patients. In contrast, relatively little is known about differences in posttransplant outcomes between patients of specific racial and ethnic populations. In this paper, we review trends in access to solid organ transplantation and posttransplant outcomes by organ type, race and ethnicity. In addition, we present an analysis of categories of factors that contribute to the racial/ethnic variation seen in kidney transplant outcomes. Disparities in minority access to transplantation among wait-listed candidates are improving, but persist for those awaiting kidney, simultaneous kidney and pancreas and intestine transplantation. In general, graft and patient survival among recipients of solid organ transplants is highest for Asians and Hispanic/Latinos, intermediate for whites and lowest for African Americans. Although much of the difference in outcomes between racial/ethnic groups can be accounted for by adjusting for patient characteristics, important observed differences remain. Age and duration of pretransplant dialysis exposure emerge as the most important determinants of survival in an investigation of the relative impact of center-related versus patient-related variables on kidney graft outcomes. [source] Meta-Analyses Qualify Metzincins and Related Genes as Acute Rejection Markers in Renal Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010S. Rödder Definition of acute renal allograft rejection (AR) markers remains clinically relevant. Features of T-cell,mediated AR are tubulointerstitial and vascular inflammation associated with excessive extracellular matrix (ECM) remodeling, regulated by metzincins, including matrix metalloproteases (MMP). Our study focused on expression of metzincins (METS), and metzincins and related genes (MARGS) in renal allograft biopsies using four independent microarray data sets. Our own cases included normal histology (N, n = 20), borderline changes (BL, n = 4), AR (n = 10) and AR + IF/TA (n = 7). MARGS enriched in all data sets were further examined on mRNA and/or protein level in additional patients. METS and MARGS differentiated AR from BL, AR + IF/TA and N in a principal component analysis. Their expression changes correlated to Banff t- and i-scores. Two AR classifiers, based on METS (including MMP7, TIMP1), or on MARGS were established in our own and validated in the three additional data sets. Thirteen MARGS were significantly enriched in AR patients of all data sets comprising MMP7, -9, TIMP1, -2, thrombospondin2 (THBS2) and fibrillin1. RT-PCR using microdissected glomeruli/tubuli confirmed MMP7, -9 and THBS2 microarray results; immunohistochemistry showed augmentation of MMP2, -9 and TIMP1 in AR. TIMP1 and THBS2 were enriched in AR patient serum. Therefore, differentially expressed METS and MARGS especially TIMP1, MMP7/-9 represent potential molecular AR markers. [source] Is Rituximab Safe to Use in Kidney Transplant Patients?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010S. C. Jordan Rituximab is an emerging therapeutic agent in transplantation, but concerns remain over proof of efficacy, safety and dosing. See article by Kamar et al on page 89. [source] Subclinical Rejection in Stable Positive Crossmatch Kidney Transplant Patients: Incidence and CorrelationsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009E. S. Kraus We reviewed 116 surveillance biopsies obtained approximately 1, 3, 6 and 12 months posttransplantation from 50 +XM live donor kidney transplant recipients to determine the frequency of subclinical cell-mediated rejection (CMR) and antibody-mediated rejection (AMR). Subclinical CMR was present in 39.7% of the biopsies at 1 month and >20% at all other time points. The presence of diffuse C4d on biopsies obtained at each time interval ranged from 20 to 30%. In every case, where histological and immunohistological findings were diagnostic for AMR, donor-specific antibody was found in the blood, challenging the long-held belief that low-level antibody could evade detection due to absorption on the graft. Among clinical factors, only recipient age was associated with subclinical CMR. Clinical factors associated with subclinical AMR were recipient age, positive cytotoxic crossmatch prior to desensitization and two mismatches of HLA DR 51, 52 and 53 alleles. Surveillance biopsies during the first year post-transplantation for these high-risk patients uncover clinically occult processes and phenotypes, which without intervention diminish allograft survival and function. [source] BAFF Is Increased in Renal Transplant Patients Following Treatment with AlemtuzumabAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009D. Bloom Alemtuzumab is a monoclonal antibody that depletes T and B cells and is used as induction therapy for renal transplant recipients. Without long-term calcineurin inhibitor (CNI) therapy, alemtuzumab-treated patients have a propensity to develop alloantibody and may undergo antibody-mediated rejection (AMR). In pursuit of a mechanistic explanation, we analyzed peripheral B cells and serum of these patients for BAFF (Blys) and BAFF-R, factors known to be integral for B-cell activation, survival, and homeostasis. Serum BAFF levels of 22/24 alemtuzumab-treated patients were above normal range, with average levels of 1967 pg/mL compared to 775 pg/mL in healthy controls (p = 0.006). BAFF remained elevated 2 years posttransplant in 78% of these patients. BAFF-R on CD19+ B cells was significantly downregulated, suggesting ligand/receptor engagement. BAFF mRNA expression was increased 2,7-fold in CD14+ cells of depleted patients, possibly linking monocytes to the BAFF dysregulation. Addition of recombinant BAFF to mixed lymphocyte cultures increased B-cell activation to alloantigen, as measured by CD25 and CD69 coexpression on CD19+ cells. Of note, addition of sirolimus (SRL) augmented BAFF-enhanced B-cell activation whereas CNIs blocked it. These data suggest associations between BAFF/BAFF-R and AMR in alemtuzumab-treated patients. [source] Predictability of Survival Models for Waiting List and Transplant Patients: Calculating LYFTAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009R. A. Wolfe ,Life years from transplant' (LYFT) is the extra years of life that a candidate can expect to achieve with a kidney transplant as compared to never receiving a kidney transplant at all. The LYFT component survival models (patient lifetimes with and without transplant, and graft lifetime) are comparable to or better predictors of long-term survival than are other predictive equations currently in use for organ allocation. Furthermore, these models are progressively more successful at predicting which of two patients will live longer as their medical characteristics (and thus predicted lifetimes) diverge. The C-statistics and the correlations for the three LYFT component equations have been validated using independent, nonoverlapping split-half random samples. Allocation policies based on these survival models could lead to substantial increases in the number of life years gained from the current donor pool. [source] Delay of Adequate Empiric Antibiotic Therapy Is Associated with Increased Mortality among Solid-Organ Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009B. Hamandi Empiric antibiotic therapy is often prescribed prior to the availability of bacterial culture results. In some cases, the organism isolated may not be susceptible to initial empiric therapy (inadequate empiric therapy or IET). In solid-organ transplant recipients, the overall incidence and clinical importance of IET is unknown. We performed a retrospective cohort study of patients admitted from 2002 to 2004. Multiple logistic regression analyses were conducted to determine associations between potential determinants and mortality. IET was administered in 169/312 (54%) patients, with a hospital mortality rate that was significantly greater than those receiving adequate therapy (24.9% vs. 7.0%; relative risk [RR] 3.55; 95% confidence interval [CI], 1.85,6.83; p < 0.001). Regression analysis demonstrated that an increasing duration of IET (adjusted odds ratio [OR] at 24 h: 1.33; 95% CI: 1.15,1.53; p < 0.001), ICU-associated infections (adjusted OR: 6.27; 95% CI: 2.79,14.09; p < 0.001), prior antibiotic use (adjusted OR: 3.56; 95% CI: 1.51,8.41; p = 0.004) and increasing APACHE-II scores (adjusted OR: 1.26; 95% CI: 1.16,1.34; p < 0.001) were independently correlated with hospital mortality. IET is common and appears to be associated with an increased hospital mortality rate in the solid-organ transplant population. [source] Prevalence of Human Herpesvirus-6 Chromosomal Integration (CIHHV-6) in Italian Solid Organ and Allogeneic Stem Cell Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009L. Potenza The unique phenomenon of human herpesvirus-6 (HHV-6) chromosomal integration (CIHHV-6) may account for clinical drawbacks in transplant setting, being misinterpreted as active infection and leading to unnecessary and potentially harmful treatments. We have investigated the prevalence of CIHHV-6 in 205 consecutive solid organ (SO) and allogeneic stem cell transplant (alloSCT) Italian patients. Fifty-two (38.5%) of 135 solid organ transplant (SOT) and 16 (22.8%) of 70 alloSCT patients resulted positive for plasma HHV-6 DNA by real-time polymerase chain reaction. Seven SOT and three alloSCT patients presented HHV-6-related diseases, requiring antivirals. Two further patients (0.9%) were identified, presenting high HHV-6 loads. The quantification of HHV-6 on hair follicles disclosed the integrated state, allowing the discontinuation of antivirals. Before starting specific treatments, CIHHV-6 should be excluded in transplant patients with HHV-6 viremia by the comparison of HHV-6 loads on different fluids and tissues. Pretransplantation screening of donors and recipients may further prevent the misdiagnosis of CIHHV-6. [source] Sleep Disordered Breathing in Renal Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009F. Mallamaci Sleep disordered breathing (SDB) is a prevalent, important nontraditional cardiovascular (CV) risk factor in end-stage renal disease patients. The prevalence of SDB in renal transplant patients is unknown. We compared polysomnographic studies in 163 transplant patients with matched samples in the general population and explored longitudinally the effect of return to dialysis after graft failure on SDB in three consecutive cases. Episodes of nocturnal hypoxemia, average and minimal O2 saturation overnight in transplant patients did not differ from those in individuals in the general population matched for age, gender and body mass index (BMI). The prevalence of moderate-to-severe SBD in these patients did not exceed the estimated prevalence of the same disturbance in the general population. The respiratory disturbance index in transplant patients was directly associated with BMI (p < 0.001). In the longitudinal study all indicators of SDB coherently increased after transplant failure. The prevalence of SDB in transplant patients does not differ from that in well-matched individuals in the general population. The favorable effect of renal transplantation on CV risk may be at least partially explained by the lack of risk excess for SDB in this population. Longitudinal observations after transplant failure are compatible with the hypothesis that renal transplantation reverses SDB. [source] Case Mix, Quality and High-Cost Kidney Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009M. J. Englesbe A better understanding of high-cost kidney transplant patients would be useful for informing value-based purchasing strategies by payers. This retrospective cohort study was based on the Medicare Provider Analysis and Review (MEDPAR) files from 2003 to 2006. The focus of this analysis was high-cost kidney transplant patients (patients that qualified for Medicare outlier payments and 30-day readmission payments). Using regression techniques, we explored relationships between high-cost kidney transplant patients, center-specific case mix, and center quality. Among 43 393 kidney transplants in Medicare recipients, 35.2% were categorized as high-cost patients. These payments represented 20% of total Medicare payments for kidney transplantation and exceeded $200 million over the study period. Case mix was associated with these payments and was an important factor underlying variation in hospital payments high-cost patients. Hospital quality was also a strong determinant of future Medicare payments for high-cost patients. Compared to high-quality centers, low-quality centers cost Medicare an additional $1185 per kidney transplant. Payments for high-cost patients represent a significant proportion of the total costs of kidney transplant surgical care. Quality improvement may be an important strategy for reducing the costs of kidney transplantation. [source] 18F-FDG-Uptake of Hepatocellular Carcinoma on PET Predicts Microvascular Tumor Invasion in Liver Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009A. Kornberg Vascular invasion of hepatocellular carcinoma (HCC) is a major risk factor for poor outcome after liver transplantation (LT). The aim of this retrospective analysis was to assess the value of preoperative positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) in liver transplant candidates with HCC for predicting microvascular tumor invasion (MVI) and posttransplant tumor recurrence. Forty-two patients underwent LT for HCC after PET evaluation. Sixteen patients had an increased 18F-FDG tumor uptake on preoperative PET scans (PET +), while 26 recipients revealed negative PET findings (PET,) pre-LT. PET, recipients demonstrated a significantly better 3-year recurrence-free survival (93%) than PET + patients (35%, p < 0.001). HCC recurrence rate was 50% in the PET + group, and 3.8% in the PET,population (p < 0.001). PET + status was identified as independent predictor of MVI [hazard ratio: 13.4]. Patients with advanced PET negative tumors and patients with HCC meeting the Milan criteria had a comparable 3-year-recurrence-free survival (80% vs. 94%, p = 0.6). Increased 18F-FDG uptake on PET is predictive for MVI and tumor recurrence after LT for HCC. Its application may identify eligible liver transplant candidates with tumors beyond the Milan criteria. [source] Incidence of JC-Virus Replication After Rituximab Therapy in Solid-Organ Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009N. Kamar No abstract is available for this article. [source] CD4+CD25+FOXP3+ Regulatory T Cells Increase De Novo in Kidney Transplant Patients After Immunodepletion with Campath-1HAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2008D. D. Bloom Campath-1H (Alemtuzumab) is an effective immunodepletion agent used in renal transplantation. To evaluate its influence on T lymphocytes during repletion, we analyzed peripheral blood from Campath-1H-treated renal allograft recipients for the presence of FOXP3+ regulatory T (Treg) cells. Flow cytometry demonstrated that CD4+CD25+FOXP3+ lymphocytes increased significantly within the CD4+ T-cell population, skewing Treg/Teff (T effector) ratios for up to several years. In contrast, Treg levels in patients treated with anti-CD25 (Basiliximab) and maintained on CsA demonstrated a sustained decrease. The increase in Tregs in Campath-1H treated patients developed independent of maintenance immunosuppression. Importantly, the increase in Tregs was not fully explained by their homeostatic proliferation, increased thymic output, or Treg sparing, suggesting de novo generation/expansion. Consistent with this, in vitro stimulation of PBMCs with Campath-1H, with or without anti-CD3, activation led to an increase in CD4+CD25+FOXP3+ cells that had suppressive capabilities. Together, these data suggest that Campath-1H promotes an increase in peripheral Tregs and may act as an intrinsic generator of Tregs in vivo. [source] Posttransplant Prophylactic Intravenous Immunoglobulin in Kidney Transplant Patients at High Immunological Risk: A Pilot StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2007D. Anglicheau The effects of posttransplant prophylactic intravenous immunoglobulin (IVIg) were investigated in renal transplant recipients at high immunological risk. Thirty-eight deceased-donor kidney transplant recipients with previous positive complement-dependent cytotoxicity crossmatch (n = 30), and/or donor-specific anti-HLA antibodies (n = 14) were recruited. IVIg (2 g/kg) was administrated on days 0, 21, 42 and 63 with quadruple immunosuppression. Biopsy-proven acute cellular and humoral rejection rates at month 12 were 18% and 10%, respectively. Glomerulitis was observed in 31% and 60% of patients at months 3 and 12, respectively, while allograft glomerulopathy rose from 3% at month 3 to 28% at 12 months. Interstitial fibrosis/tubular atrophy increased from 18% at day 0 to 51% and 72% at months 3 and 12 (p < 0.0001). GFR was 50 ± 17 mL/min/1.73 m2 and 48 ± 17 mL/min/1.73 m2 at 3 and 12 months. PRA decreased significantly after IVIg (class I: from 18 ± 27% to 5 ± 12%, p < 0.01; class II: from 25 ± 30% to 7 ± 16%, p < 0.001). Patient and graft survival were 97% and 95%, respectively and no graft was lost due to rejection (mean follow-up 25 months). In conclusion, prophylactic IVIg in high-immunological risk patients is associated with good one-year outcomes, with adequate GFR and a profound decrease in PRA level, but a significant increase in allograft nephropathy. [source] Pharmacokinetic and Pharmacodynamic Comparison of Enteric-Coated Mycophenolate Sodium and Mycophenolate Mofetil in Maintenance Renal Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2007K. Budde The aim of this single-center crossover substudy was to assess pharmacokinetics and pharmacodynamics [inosine 5,-monophosphate dehydrogenase (IMPDH) activity] of enteric-coated mycophenolate sodium (EC-MPS) and mycophenolate mofetil (MMF) at steady-state conditions. Stable maintenance renal transplant patients on 1 g MMF b.i.d. participating in a double-blind, multicenter study, were randomized to receive EC-MPS (720 mg b.i.d.) or continue receiving MMF (1000 mg b.i.d.) for 12 months. Thereafter, all patients (n = 18) received 720 mg EC-MPS b.i.d. Area under the plasma mycophenolic acid (MPA) concentration,time curve with EC-MPS (57.4 ± 15.0 ,g h/mL) fulfilled bioequivalence criteria (geometric mean 0.98 (90% CI: 0.87,1.11) compared to MMF (58.4 ± 14.1 ,g h/mL). Consistent with the delayed release characteristics of EC-MPS, peak MPA concentration (geometric mean 0.89; 90% CI: 0.70,1.13) occurred approximately 0.5 h later (p < 0.05) and predose MPA levels (geometric mean 2.10; 90% CI: 1.51,2.91) were higher and more variable, not fulfilling bioequivalence criteria. IMPDH activity inversely followed MPA concentrations and was inhibited to a similar degree (approximately 85%) by both formulations. The calculated value for 50% IMPDH inhibition was identical for both drugs. In conclusion, equimolar doses of EC-MPS and MMF produce equivalent MPA exposure, while the delayed release formulation of EC-MPS exhibits more variable predose levels and Tmax. Overall, IMPDH activity reflected MPA pharmacokinetics. [source] Acute Cellular Rejection with CD20-Positive Lymphoid Clusters in Kidney Transplant Patients Following Lymphocyte DepletionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2007L. K. Kayler Lymphoid clusters (LC) containing CD20-positive B cells in kidney allografts undergoing acute cellular rejection (ACR) have been identified in small studies as a prognostic factor for glucocorticoid resistance and graft loss. Allograft biopsies obtained during the first episode of ACR in 120 recipients were evaluated for LC, immunostained with CD20 antibody, and correlated with conventional histopathologic criteria, response to treatment and outcome. LC were found in 71 (59%) of the 120 biopsies. All contained CD20 positive B cells that accounted for 5,90% of the LC leukocyte content. The incidence of LC was highest in the patients who had no lymphoid depletion or had been treated with Thymoglobulin preconditioning (79% vs. 75%, respectively) compared to 37% in patients pretreated with Campath (p = 0.0001). Banff 1a/1b ACR were more frequent in the LC-positive than the LC-negative group (96% vs. 80%, respectively; p = 0.0051). With a posttransplant follow-up of 953 ± 430 days, no significant differences were detected between LC-postitive and LC-negative groups in time to ACR, steroid resistance, serum creatinine and graft loss. CD20+LC did not portend glucocorticoid resistance or worse short to medium term outcomes. CD20+LC may represent a heterogenous collection in which there may be a small still to be fully defined unfavorable subgroup. [source] Methylprednisolone Exposure in Pediatric Renal Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2006P. Seikku Glucocorticoid (GC) dosing is commonly based on body mass or surface area in children, although the drug effects appear to correlate with steroid exposure, rather than dose. We compared the area under the serum concentration,time curve (AUC) of methylprednisolone (MP) with a recombinant cell bioassay measuring serum glucocorticoid bioactivity (GBA), in prediction of side effects in 16 pediatric patients (5.4,18.4 years of age) 2.0,14.9 years after renal transplantation (TX). They received 0.3 mg/kg of MP orally and timed blood samples were drawn up to 8 h postdose. Serum MP concentrations correlated moderately with GBA (r= 0.65, p < 0.0001) with best linear fit at 6 and 8 h (r= 0.72, 0.79, respectively, p < 0.001). MP-AUCt = 0,8 and GBAt = 6 were significantly greater in patients who gained excessive weight soon after TX. Change in growth after TX was inversely correlated with MP-AUC (r= 0.73, p < 0.05) and GBAt = 6 (r= 0.62, p < 0.05). No correlation of MP-AUC or GBA was found with blood glucose or serum lipid concentrations, glomerular filtration rate, bone mineral density or graft histology. In conclusion, GC exposure varies individually and dosing should be adjusted accordingly to control the adverse effects. GBA might provide a complementary tool for monitoring GC exposure but further studies are needed. [source] Dendritic Cell Deficiency in the Blood of Kidney Transplant Patients on Long-Term Immunosuppression: Results of a Prospective Matched-Cohort StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2005Holger Hackstein Evidence from in vitro studies suggests that immunosuppressive drugs interfere with key functions of dendritic cells (DCs), but the in vivo relevance of these findings is elusive. We prospectively analyzed the major DC precursor subsets in the blood of kidney transplant recipients on long-term immunosuppression (,1 year). A total of 87 patients were compared to 87 age- and sex-matched controls. Total DC numbers and the precursor subsets, myeloid type 1 DCs, myeloid type 2 DCs (mDC1, mDC2) and plasmacytoid DCs (pDCs) were identified by four color flow cytometry. Long-term immunosuppression was associated with significant reduction of all major DC subsets in comparison to healthy controls (mDC1 p < 0.001; mDC2 p < 0.0001; two-tailed Mann-Whitney U -test) with the strongest negative impact on pDCs (p < 0.00001). In contrast, total leukocyte numbers were not significantly affected. Analysis of the relative impact of different agents revealed a significant impact of prednisolone on pDCs (p = 0.009) and mDCs2 (p = 0.006). The functional relevance of pDC deficiency was confirmed independently by Interferon-alpha analysis after Toll-like receptor 7 (p , 0.001) and 9 (p < 0.05) stimulation. These results indicate for the first time a profound negative impact of long-term immunosuppression on major DC subsets in kidney transplant recipients. DC deficiency may have important implications with respect to viral infections and tumor development. [source] | ||||||||||||||||||||||||||||||||||