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Transplant Vasculopathy (transplant + vasculopathy)
Selected AbstractsComposite Tissue Vasculopathy and Degeneration Following Multiple Episodes of Acute Rejection in Reconstructive TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010J. V. Unadkat Transplant vasculopathy has not been systematically investigated in composite tissue allotransplantation (CTA). The impact of multiple acute rejections (ARs) on long-term graft outcomes in reconstructive transplantation remains unknown. This study in a rat hind-limb allotransplantation model systematically analyzes vasculopathy and tissue-specific pathological changes secondary to multiple AR episodes. LEW rats were transplanted with BN rat hind limbs and treated as follows: Group 1 (Iso): isografts. Group 2 (CsA): Cyclosporine (CsA) qd; Group 3 (mult AR): CsA and dexamethasone only when AR was observed. No AR was observed in Groups 1 and 2. Multiple AR were observed in Group 3, and each episode was completely reversed (clinically) with pulsed CsA + dexamethasone treatment. Group 3 animals demonstrated significant vascular lesions along with skin and muscle atrophy, upregulation of profibrotic gene expression and fibrosis when compared to Groups 1 and 2. In addition, allograft bone was sclerotic, weak and prone to malunion and nonunion. Interestingly, vasculopathy was a late finding, whereas muscle atrophy with macrophage infiltration was seen early, after only a few AR episodes. Taken together, multiple AR episodes lead to vasculopathy and tissue-specific pathology in CTA. This is the first evidence of ,composite tissue vasculopathy and degeneration (CTVD)' in CTA. [source] Focal Atrial Tachycardia Originating from the Donor Superior Vena Cava after Bicaval Orthotopic Heart TransplantationPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 8 2010HAW-KWEI HWANG M.D. An 11-year-old boy, who underwent bicaval orthotopic heart transplantation for idiopathic dilated cardiomyopathy, had a focal atrial tachycardia originating from the donor superior vena cava. The pathogenesis of this tachycardia may be related to transplant rejection or transplant vasculopathy. Radiofrequency catheter ablation can eliminate this unique tachycardia and result in hemodynamic improvement. (PACE 2010; e68,e71) [source] Proton Pump Inhibitors Reduce Mycophenolate Exposure in Heart Transplant Recipients,A Prospective Case-Controlled StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009S. Kofler This prospective study investigates the impact of proton pump inhibitors (PPI) on mycophenolic acid (MPA) pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) and tacrolimus. MPA plasma concentrations at baseline (C0 h), 30 min (C0.5 h), 1(C1 h) and 2 h (C2 h) were obtained by high-performance liquid chromatography (HPLC) in 22 patients treated with pantoprazole 40 mg and MMF 2000 mg. Measurements were repeated 1 month after pantoprazole withdrawal. A four-point limited-sampling strategy was applied to calculate the MPA area under the curve (MPA-AUC). Predose MPA concentrations with PPI were 2.6 ± 1.6 mg/L versus 3.4 ± 2.7 mg/L without PPI (p = ns). Postdose MPA concentrations were lower with PPI at C0.5 h (8.3 ± 5.7 mg/L vs. 18.3 ± 11.3 mg/L, p = 0.001) and C1 h (10.0 ± 5.6 mg/L vs. 15.8 ± 8.4 mg/L, p = 0.004), without significant differences at C2 h (8.3 ± 6.5 mg/L vs. 7.6 ± 3.9 mg/L). The MPA-AUC was significantly lower with PPI medication (51.2 ± 26.6 mg × h/L vs. 68.7 ± 30.3 mg × h/L; p = 0.003). The maximum concentration of MPA (MPA-Cmax) was lower (12.2 ± 7.5 mg/L vs. 20.6 ± 9.3 mg/L; p = 0.001) and the time to reach MPA-Cmax (tmax) was longer with PPI (60.0 ± 27.8 min vs. 46.4 ± 22.2 min; p = 0.05). This is the first study to document an important drug interaction between a widely used immunosuppressive agent and a class of drugs frequently used in transplant patients. This interaction results in a decreased MMF drug exposure which may lead to patients having a higher risk for acute rejection and transplant vasculopathy. [source] Donor and Recipient Origin of Mesenchymal and Endothelial Cells in Chronic Renal Allograft RemodelingAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009H. Rienstra Chronic transplant dysfunction (CTD) is the leading cause for limited kidney graft survival. Renal CTD is characterized by interstitial and vascular remodeling leading to interstitial fibrosis, tubular atrophy and transplant vasculopathy (TV). The origin of cells and pathogenesis of interstitial and vascular remodeling are still unknown. To study graft-versus-recipient origin of interstitial myofibroblasts, vascular smooth muscle cells (SMCs) and endothelial cells (ECs), we here describe a new rat model for renal CTD using Dark Agouti kidney donors and R26 human placental alkaline phosphatase transgenic Fischer344 recipients. This model showed the development of CTD within 12 weeks after transplantation. In interstitial remodeling, both graft- and recipient-derived cells contributed to a similar extent to the accumulation of myofibroblasts. In arteries with TV, we observed graft origin of neointimal SMCs and ECs, whereas in peritubular and glomerular capillaries, we detected recipient EC chimerism. These data indicate that, within the interstitial and vascular compartments of the transplanted kidney, myofibroblasts, SMCs and ECs involved in chronic remodeling are derived from different sources and suggest distinct pathogenetic mechanisms within the renal compartments. [source] Chronic rejection with or without transplant vasculopathyCLINICAL TRANSPLANTATION, Issue 3 2003Yvo WJ Sijpkens Abstract: Background: Chronic allograft nephropathy (CAN) is defined and graded in the Banff '97 scheme by the severity of interstitial fibrosis and tubular atrophy. It has been denoted that chronic rejection can be diagnosed if the typical vascular lesions are seen, consisting of fibrointimal thickening. We observed several patients who developed CAN without vascular changes or signs of cyclosporine toxicity. Therefore, we assessed the risk factor profiles of CAN with and without transplant vasculopathy. Methods: A cohort of 654 cadaveric renal transplants performed between 1983 and 1997 that functioned for more than 6 months was studied. Fifty-four transplants had CAN defined by a significant decline in renal function together with interstitial fibrosis and tubular atrophy without signs of cyclosporine nephrotoxicity or recurrent disease. Using the Banff chronic vascular (CV) score, 23 of 54 cases (43%) had a chronic vasculopathy score of 0 or 1 whereas 31 cases (57%) had a CV score of 2 or 3. Applying multivariate logistic regression, predictor variables of the two groups were compared with 231 transplants with a stable function for at least 5 yr. Results: Graft histology was obtained at a mean of 2.4 and 2.9 yr after transplantation in the group with or without vasculopathy, respectively. Acute rejection episodes (AREs) after 3 months post-transplantation were the strongest risk factor for both forms of CAN, odds ratio (OR) 14.7 (6.0,36.0). CAN with vasculopathy was also associated with transplants performed in the 1980s, OR 4.95 (1.65,14.9) and with creatinine clearance at 6 months, OR 0.58 (0.44,0.75) per 10 mL/min increase. In contrast, young recipient age, OR 0.69 (0.47,0.99) per 10-yr increase, and the presence of panel reactive antibodies at the time of transplantation, OR 1.26 (1.08,1.47) per 10% increase, were independent risk factors for CAN without vasculopathy. Conclusions: After exclusion of cyclosporine toxicity or recurrent disease CAN occurred without moderate or severe transplant vasculopathy in 43% of the cases. The correlation with young recipient age, sensitization and late ARE suggest an immune pathogenesis, consistent with chronic rejection. [source] | ||||||||||