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Les derniers abstracts de la revue Transplantation - Current Issue : |
Date de mise en ligne : Mercredi 31 décembre 1969
Hougardy, Jean-Michel; de Jonge, Hylke; Kuypers, Dirk; Abramowicz, Daniel
The Once-Daily Formulation of Tacrolimus: A Step Forward in Kidney Transplantation?
Nonadherence is a critical issue in transplantation. Recently, Astellas designed a once-daily-extended release formulation of tacrolimus (Tac). Despite initial reports showing bioequivalence of Tac once-daily (Advagraf) with the original formulation requiring twice-daily intake (Tac twice-daily, Prograf), several groups have now shown a sustained decrease in Tac exposure upon conversion from Prograf to Advagraf. Here, we discuss the possible reasons for this observation and how it could affect the expected benefits of Advagraf, and we comment on the fact that a similar lack of bioequivalence might prevail with generic immunosuppressive drugs.
Date de mise en ligne : Mercredi 31 décembre 1969
Rose, Marlene L.; West, Lori J.
Accommodation: Does it Apply to Human Leukocyte Antigens?
The term “accommodation†was invoked to describe endothelial cell resistance to antibody-mediated rejection after ABO-incompatible kidney or experimental xenograft transplantation. Currently, there is much interest in how to achieve successful human leukocyte antigen (HLA)-incompatible allograft transplantation in HLA-sensitized patients and how to treat antibody-mediated rejection after ABO-compatible HLA-incompatible allotransplantation. The term “accommodation†is often used interchangeably to describe patients who have donor-specific ABO or HLA alloantibodies in the absence of damage to their allograft. Here, we suggest that there are important differences between the immune responses to protein versus carbohydrate antigens and that graft HLA molecules may respond differently to antibodies (and antibody isotypes) than ABO antigens. Neither the mechanisms nor a phenotype of accommodation have been defined fully. Further research is needed to define mechanisms of both resistance and susceptibility to antibody-mediated injury and to predict under which circumstances allograft accommodation may occur.
Date de mise en ligne : Mercredi 31 décembre 1969
Claas, Frans H.J.
It Takes Two to Tango: Both Donor and Recipients' Immune Repertoire Affect Outcome of Renal Transplants
No abstract available
Date de mise en ligne : Mercredi 31 décembre 1969
Pech, Thomas; Fujishiro, Jun; Finger, Tobias; Ohsawa, Ichiro; Praktiknjo, Michael; Abu-Elmagd, Kareem; von Websky, Martin; Overhaus, Marcus; Kalff, Joerg C.; Schaefer, Nico
Combination Therapy of Tacrolimus and Infliximab Reduces Inflammatory Response and Dysmotility in Experimental Small Bowel Transplantation in Rats
Background. Intestinal transplantation initiates a functionally relevant inflammatory response by activation of resident macrophages within the muscularis associated with dysmotility. Infliximab is used successfully as a potent anti-inflammatory agent for the treatment of chronic inflammatory bowel diseases and as rescue therapy in acute steroid-resistant rejection in selected settings in clinical small bowel transplantation. We hypothesize that additional perioperative treatment with infliximab diminishes initiation of the inflammatory cascade and improves motility in small bowel grafts using a standard tacrolimus immunosuppressive protocol.
Methods. Orthotopic intestinal transplantation was performed in rats. In two treatment groups (24/168 hr), infliximab was administered intravenously directly after reperfusion and tacrolimus was injected intramuscularly after transplantation and once a day. Two other treatment groups (24/168 hr) received standard immunosuppressive therapy with tacrolimus. Isogenic and allogenic transplanted vehicle-treated animals (24/168 hr) and native gut served as control.
Results. Infliximab-treated grafts exhibited significantly less leukocyte infiltration at 24/168 hr after transplantation and at 168 hr significantly less apoptosis in the tunica muscularis compared with tacrolimus monotherapy. Additional infliximab treatment resulted in increased smooth muscle contractility (30%) after 24 hr compared with tacrolimus control.
Conclusions. Dysmotility of transplanted small bowel results from reperfusion injury and acute rejection. Additional perioperative treatment with infliximab reduces early unspecific inflammatory responses and complements immunosuppressive therapy with tacrolimus.
Date de mise en ligne : Mercredi 31 décembre 1969
Canet, Emmanuel; Devallière, Julie; Gérard, Nathalie; Karam, George; Giral, Magali; Charreau, Béatrice; Coupel, Stéphanie
Profiling Posttransplant Circulating Antibodies in Kidney Transplantation Using Donor Endothelial Cells
Background. Pathogenesis of antibody (Ab) responses to transplant are yet not well defined. This study aimed to detect and to analyze posttransplant circulating allo-Abs reacting toward graft endothelial cells (ECs) using primary EC cultures prospectively isolated from the transplant donor at the time of transplantation.
Methods. This study shows a retrospective analysis performed using a dedicated EC crossmatch (ECXM) assay that we developed for the experimental assessment of donor-specific EC-reactive Abs. Donor-specific ECXM was performed by flow cytometry on posttransplant sera (n=256) from an historical cohort of 22 kidney allograft recipients.
Results. In this study, we show that 27.3% (6/22) of recipients have a positive ECXM that strictly correlates (100%, 6/6) with the presence of anti-human leukocyte antigen (HLA) Abs posttransplantation. ECXM identifies both donor-specific Abs (DSA; 50%) and non-DSA (50%) reactive to EC. DSA and non-DSA are mostly IgG1 and exhibit peak titers ranging from 1/8 to 1/1024. ECXM indicates that DSA correspond to anti-HLA class II Abs; this immunization is late (M3-M60) but persistent (still detected at M60). In contrast, non-DSA are non-HLA-type Abs reacting with third-party EC and reflecting an early but transient immunization (ended at M3-M12). Our findings demonstrate selective regulatory pathways initiated by anti-HLA class II and non-DSA in graft EC reflected by CCR4 and interleukin 1β up-regulation, respectively.
Conclusions. We provide evidence that circulating Abs in HLA-sensitized transplant recipients include both DSA and non-HLA/non-DSA able to bind to graft EC and induce specific gene transcription.
Date de mise en ligne : Mercredi 31 décembre 1969
Lin, Han-Chen; Lee, Tsai-Kun; Tsai, Chia-Chin; Lai, I-Rue; Lu, Kuo-Shyan
Ischemic Postconditioning Protects Liver From Ischemia-Reperfusion Injury by Modulating Mitochondrial Permeability Transition
Background. We tested the effectiveness of ischemic postconditioning (iPoC) in mitigating ischemia-reperfusion (I/R) injury of liver and the mechanism involves inhibiting the opening of the mitochondrial permeability transition pore (mPTP).
Methods. iPoC, performed by three cycles of 1 min I/R of the liver, was tested on a partial liver I/R model on rats. The serum alanine transaminase levels, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, cytochrome c release, the formation of 4-hydroxy-2-nonnenal-modified proteins, and mitochondrial membrane potential (Δψm) were measured. Atractyloside (ATR) and NIM811, which modify the opening of mPTP, were administered in selected groups.
Results. iPoC, and NIM811, diminished the elevation of serum alanine transaminase level after I/R injury (174.0±28.3 U/L for iPoC; 94.3±25.4 U/L for control+NIM811) when compared with others (416.3±16.7 U/L for control, 557.0±86.7 U/L for iPoC+ATR, P<0.05). The expressions of cytosolic cytochrome c after I/R injury were decreased in iPoC and control+NIM811 groups when compared with others. After I/R, the apoptosis and the 4-hydroxy-2-nonnenal-modified proteins were attenuated in iPoC group when compared (apoptotic counts/50 HPF: 723.3±98.7 for iPoC, 1274±201.2 for control, 1057.6±39 for iPoC+ATR, P<0.05). The Δψm measured by flow cytometry was better preserved in iPoC and NIM811 groups.
Conclusions. iPoC attenuated cell deaths after I/R injury of liver. The protective effects were negated by the addition of ATR—a mPTP opener—and mimicked by injection of NIM811—a mPTP opening inhibitor. The study indicated iPoC conferred protection by modulating mPTP.
Date de mise en ligne : Mercredi 31 décembre 1969
Chou, Hong-Shiue; Hsieh, Ching-Chuan; Charles, Ronald; Wang, Lianfu; Wagner, Timothy; Fung, John J.; Qian, Shiguang; Lu, Lina L.
Myeloid-Derived Suppressor Cells Protect Islet Transplants by B7-H1 Mediated Enhancement of T Regulatory Cells
Background. Side effects of lifetime immunosuppression for cell transplants often outweigh the benefits; therefore, induction of transplant tolerance is needed. We have shown that cotransplantation with myeloid-derived suppressor cells (MDSC) effectively protect islet allografts from rejection without requirement of immunosuppression. This study was to investigate the underlying mechanisms.
Methods. MDSC were generated by addition of hepatic stellate cells from various stain mice into dendritic cell (DC) culture. The quality of MDSC was monitored by phenotype and function analyses. MDSC mixed with islet allografts were transplanted into diabetic recipients. T-cell response was analyzed after transplantation by using flow and histochemical analyses, and was compared with islet alone and islet/DC transplant groups. B7-H1 knockout mice were used to determine the role of B7-H1 on MDSC in regulation of T-cell response.
Results. Cotransplantation with MDSC (not DC) effectively protected islet allografts without requirement of immunosuppression. This is associated with attenuation of CD8 T cells in the grafts and marked expansion of regulatory T (Treg) cells, which contributed to MDSC-induced T-cell hyporesponsiveness. Antigen-specific Treg cells were prone to accumulate in lymphoid organs close to the grafts. Both in vitro and in vivo data demonstrated that B7-H1 was absolutely required for MDSC to exert immune regulatory activity and induction of Treg cells.
Conclusion. The described approach holds great clinical application potential and may overcome the limitation of requiring chronic administration of immunosuppression in cell transplants. Understanding the underlying mechanisms will facilitate the development of this novel therapeutic strategy.
Date de mise en ligne : Mercredi 31 décembre 1969
Jankowska-Gan, Ewa; Sheka, Adam; Sollinger, Hans W.; Pirsch, John D.; Hofmann, R. Michael; Haynes, Lynn D.; Armbrust, Michael J.; Mezrich, Joshua D.; Burlingham, William J.
Pretransplant Immune Regulation Predicts Allograft Outcome: Bidirectional Regulation Correlates With Excellent Renal Transplant Function in Living-Related Donor-Recipient Pairs
Background. Tolerance to noninherited maternal antigens has provided clinical advantage when kidney transplants are exchanged between siblings but not when mother herself is the donor. This paradox prompted us to revisit the “two-way†hypothesis of transplant tolerance—that the immune status of both the organ recipient and the organ donor critically influences allograft outcome.
Methods. We obtained peripheral blood monocyte cells from 29 living donor-recipient pairs before transplant and used the trans-vivo-delayed type hypersensitivity assay to measure immune regulation in both the recipient antidonor and donor antirecipient directions.
Results. We found preexisting bidirectional regulation in all human leukocyte antigen (HLA)-identical sibling pairs tested (7/7), and one half (9/18) of the HLA haploidentical pairs. No significant regulation was found in four control living unrelated and two HLA haploidentical living-related donor recipient pairs, whereas unidirectional regulation was found in the remaining seven haploidentical pairs. Of the nine HLA haploidentical transplants with unidirectional or no pretransplant regulation, seven had an acute rejection episode and four of these experienced graft loss. In contrast, of the nine HLA haploidentical transplants with bidirectional regulation, only one had rejection. Renal function for the latter group was similar to HLA-identical kidney recipients at 3 years posttransplant. Significantly (P<0.05) lower mean serum creatinine values in bidirectional regulators were noted as early as 4 months and this difference became more pronounced at 12 (P<0.005) and 36 months (P<0.0001).
Conclusions. Contrary to the belief that only the recipient's immune status matters, the data indicate that pretransplant immune status of both donor and recipient influence posttransplant outcome.
Date de mise en ligne : Mercredi 31 décembre 1969
Sood, Puneet; Senanayake, Shamila; Sujeet, Kumar; Medipalli, Radhika; Saad, Ehab; Vasudev, Brahm; Bresnahan, Barbara A.; Johnson, Christopher P.; Hariharan, Sundaram
Lower Prevalence of BK Virus Infection in African American Renal Transplant Recipients: A Prospective Study
Background. Because the occurrence of BK virus (BKV) nephritis is far less frequent than BK viremia or viruria, analysis of risk factors for BKV nephritis as an endpoint could lead to erroneous findings. We undertook a prospective study to evaluate the risk factors for the occurrence of BKV infections using BK viruria and viremia as endpoints.
Methods. Two hundred forty renal only transplant recipients were prospectively enrolled into our institutional review board-approved single center study to evaluate various aspects of posttransplant BKV infection. All patients were followed up for a minimum of 6 months posttransplant.
Results. Of the 240 subjects, 154 were whites, 61 African Americans, and 25 belonged to other races. A total of 94 developed BKV infection (any degree of BK viruria or viremia) whereas 146 developed no infection. Among these, 33 had BK viruria alone, 61 had BK viremia with viruria and 25 had significant viremia defined as BKV DNA more than 10,000 copies/mL of plasma. Lower proportion of African Americans developed BKV infection, 14 of 61 (23%), as opposed to whites, 67 of 154 (47%). Logistic regression model showed lower risk of any BKV infection in African American recipient race (OR, 0.38; 95% CI, 0.17–0.82; P=0.016) and higher risk of significant BKV infection with occurrence of acute rejection (OR, 3.9; 95% CI, 1.31–11.8; P=0.015). The Kaplan-Meier analysis shows a trend toward greater freedom from BKV infection in African Americans as opposed to other racial groups (P=0.33).
Conclusion. Renal transplant recipients of African American race had a lower risk of posttransplant BKV infection compared with whites, independent of other confounding risk factors.
Date de mise en ligne : Mercredi 31 décembre 1969
Hernández, Domingo; Pérez, Germán; Marrero, Domingo; Porrini, Esteban; Rufino, Margarita; Manuel González-Posada, José; Delgado, Patricia; Torres, Armando
Early Association of Low-Grade Albuminuria and Allograft Dysfunction Predicts Renal Transplant Outcomes
Background. Data on the combined associations of albuminuria and estimated glomerular filtration rate (eGFR) with renal transplant outcomes are limited. Our objective was to explore how renal transplant outcomes could be predicted by a combined variable of early low-grade albuminuria and allograft dysfunction.
Methods. We studied a cohort of adult deceased-donor kidney transplant recipients who were subdivided into four groups according to median albuminuria (100 mg/day, interquartile range, 0–470 mg/day) and median eGFR (60 mL/min/1.73 m2; interquartile range, 30–73 mL/min/1.73 m2) at third month posttransplantation as follows: group I (albuminuria <100 and eGFR >60, n=238); group II (albuminuria ≥100 and eGFR >60, n=151); group III (albuminuria <100 and eGFR ≤60; n=167); and group IV (albuminuria ≥100 and eGFR ≤60, n=228).
Results. Death-censored graft survival was significantly lower in group IV compared with the rest (P<0.0001). Multivariate Cox regression analysis using fixed and time-dependent covariates showed that the combination of low-grade albuminuria and lower eGFR was associated with graft failure (hazard ratio, 2.2, 95% confidence interval, 1.3–3.7; P=0.003). Likewise, but to a lesser extent, the risk of mortality was increased for group IV (hazard ratio, 1.7, 95% confidence interval, 1.01–2.8; P=0.042).
Conclusions. Early association of low-grade albuminuria and allograft dysfunction represents an important risk factor of graft failure and mortality. This additive effect should be considered to identify individuals at risk for adverse kidney transplantation outcomes.
Date de mise en ligne : Mercredi 31 décembre 1969
Fayek, Sameh A.; Keenan, Jeffrey; Haririan, Abdolreza; Cooper, Matthew; Barth, Rolf N.; Schweitzer, Eugene; Bromberg, Jonathan S.; Bartlett, Stephen T.; Philosophe, Benjamin
Ureteral Stents Are Associated With Reduced Risk of Ureteral Complications After Kidney Transplantation: A Large Single Center Experience
Background. Controversy exists regarding the benefit of ureteral stents in kidney transplantation. We aimed to examine the association of stents with risk of ureteral complications, particularly in relationship with donor type.
Methods. Kidney transplants from 2005 to 2009 were evaluated (n=1224). Patients with previous or simultaneous nonkidney transplants, death, or lost to follow-up within 90 days were excluded, unless already developed a ureteral complication. Only cases with a single extravesical ureteroneocystostomy were included. The cohort (n=961) was divided into stent (32.2%) and no-stent (67.7%) groups. Poisson regression was used to examine the association of stent with ureteral complications (leak or stricture) and urinary tract infections (UTI).
Results. Ureteral complication rate was 1.9% in stent versus 5.8% in no-stent group (P=0.007). UTI rate was 14.2% with stent versus 7.9% without stent (P=0.003). Stent use was independently associated with reduction in ureteral complications (incidence rate ratios [IRR], 0.40; P=0.04; 95% confidence interval [CI], 0.17–0.96) and an increase in UTI risk (IRR, 1.79; P=0.006; 95% CI, 1.18–2.74). Stent protective effect was primarily related to reduction in stricture risk (IRR, 0.23; P<0.05; 95% CI, 0.05–0.99). Stents were associated with a decrease in ureteral complications in deceased donor recipients (IRR, 0.34; P=0.03; 95% CI, 0.13–0.88), but not living donors (IRR, 1.24; P=0.84; 95% CI, 0.15–10.2).
Conclusions. Ureteral stents are associated with a significant reduction in ureteral complications but increases UTI risk. Routine stenting in deceased donor transplants is recommended as its protective effect was observed in this group. The value of stents in living donor transplants warrants further investigation.
Date de mise en ligne : Mercredi 31 décembre 1969
Aharinejad, Seyedhossein; Salama, Mohamed; Rödler, Susanne; Ehrlich, Marek; Zuckermann, Andreas; Laufer, Guenther
Low Serum IGF-1 Is a Risk Factor for Cardiac Allograft Vasculopathy in Cardiac Transplant Recipients
Background. Cardiac allograft vasculopathy (CAV) has an incidence of 43% at 8 years after heart transplantation with extremely limited treatment options and unclear pathogenesis. CAV constitutes a significant complication that limits the long-term survival of heart recipients. Insulin-like growth factor-1 (IGF-1) is associated with different cardiovascular diseases; however, its role in CAV pathogenesis remains unknown.
Methods. Serum samples of 10 matched recipients with CAV and 10 with no-CAV were initially screened with a protein array. Subsequently, IGF-1- and IGF-binding protein-3 (IGFBP-3) were analyzed using enzyme-linked immunosorbent assay in 44 randomly selected CAV and 50 no-CAV patients at two time points.
Results. The initial screening showed that IGF-1 and IGFBP-3 are differentially expressed in CAV compared with no-CAV patients (P=0.037 and P<0.0001, respectively). Subsequent enzyme-linked immunosorbent assay analyses indicated that serum IGF-1 protein concentrations were significantly lower in CAV patients (159.7±114 ng/mL) as compared with no-CAV patients (234.1±136 ng/mL; P=0.02). Serum IGFBP-3 protein concentrations were significantly lower in CAV (0.46±0.37 mg/L) as compared with no-CAV patients (1.03±0.73 mg/L; P=0.04). Multivariate logistic regression analyses showed that IGF-1 (odds ratio, 0.89; P=0.04) and IGFBP-3 (odds ratio, 0.09; P=0.03) are independent risk factors for CAV.
Conclusion. Low IGF-1 and IGFPB-3 serum concentrations are associated with CAV. The assessment of serum IGF-1 and IGFPB-3 might be beneficial in identifying cardiac allograft recipients who are prone to develop CAV. Moreover, IGF-1 might be a useful therapy that could protect cardiac allografts against CAV.
Date de mise en ligne : Mercredi 31 décembre 1969
Watson, Christopher J. E.; Johnson, Rachel J.; Birch, Rhiannon; Collett, Dave; Bradley, J. Andrew
A Simplified Donor Risk Index for Predicting Outcome After Deceased Donor Kidney Transplantation
Background. We sought to determine the deceased donor factors associated with outcome after kidney transplantation and to develop a clinically applicable Kidney Donor Risk Index.
Methods. Data from the UK Transplant Registry on 7620 adult recipients of adult deceased donor kidney transplants between 2000 and 2007 inclusive were analyzed. Donor factors potentially influencing transplant outcome were investigated using Cox regression, adjusting for significant recipient and transplant factors. A United Kingdom Kidney Donor Risk Index was derived from the model and validated.
Results. Donor age was the most significant factor predicting poor transplant outcome (hazard ratio for 18–39 and 60+ years relative to 40–59 years was 0.78 and 1.49, respectively, P<0.001). A history of donor hypertension was also associated with increased risk (hazard ratio 1.30, P=0.001), and increased donor body weight, longer hospital stay before death, and use of adrenaline were also significantly associated with poorer outcomes up to 3 years posttransplant. Other donor factors including donation after circulatory death, history of cardiothoracic disease, diabetes history, and terminal creatinine were not significant. A donor risk index based on the five significant donor factors was derived and confirmed to be prognostic of outcome in a validation cohort (concordance statistic 0.62). An index developed in the United States by Rao et al., Transplantation 2009; 88: 231–236, included 15 factors and gave a concordance statistic of 0.63 in the UK context, suggesting that our much simpler model has equivalent predictive ability.
Conclusions. A Kidney Donor Risk Index based on five donor variables provides a clinically useful tool that may help with organ allocation and informed consent.
Date de mise en ligne : Mercredi 31 décembre 1969
Morrow, William Robert; Frazier, Elizabeth A.; Mahle, William T.; Harville, Terry O.; Pye, Sherry E.; Knecht, Kenneth R.; Howard, Emily L.; Neal Smith, R.; Saylors, Robert L.; Garcia, Xiomara; Jaquiss, Robert D.B.; Woodle, E. Steve
Rapid Reduction in Donor-Specific Anti-Human Leukocyte Antigen Antibodies and Reversal of Antibody-Mediated Rejection With Bortezomib in Pediatric Heart Transplant Patients
Background. High titer donor-specific antibodies (DSA) and positive crossmatch in cardiac transplant recipients is associated with increased mortality from antibody-mediated rejection (AMR). Although treatment to reduce anti-human leukocyte antigen antibodies using plasmapheresis, intravenous immunoglobulin, and rituximab has been reported to be beneficial, in practice these are often ineffective. Moreover, these interventions do not affect the mature antibody producing plasma cell. Bortezomib, a proteasome inhibitor active against plasma cells, has been shown to reduce DSA in renal transplant patients with AMR. We report here the first use of bortezomib for cardiac transplant recipients in four pediatric heart recipients with biopsy-proven AMR, hemodynamic compromise, positive crossmatch, and high titer class I DSA.
Methods. Patients received four intravenous dose of bortezomib (1.3 mg/m2) over 2 weeks with plasmapheresis and rituximab. DSA specificity and strength (mean fluorescence intensity) was determined with Luminex. All had received previous treatment with plasmapheresis, intravenous immunoglobulin, and rituximab that was ineffective.
Results. AMR resolved in all patients treated with bortezomib with improvement in systolic function, conversion of biopsy to C4d negative in three patients and IgG negative in one patient, and a prompt, precipitous reduction in DSAs. In three patients who received plasmapheresis before bortezomib, plasmapheresis failed to reduce DSA. In one case, DSA increased after bortezomib but decreased after retreatment.
Conclusions. Bortezomib reduces DSA and may be an important adjunct to treatment of AMR in cardiac transplant recipients. Bortezomib may also be useful in desensitization protocols and in prevention of AMR in sensitized patients with positive crossmatch and elevated DSA.
Date de mise en ligne : Mercredi 31 décembre 1969
Chen, Yan; Sampaio, Marcelo S.; Yang, Jae Wook; Min, David; Hutchinson, Ian V.
Genetic Polymorphisms of the Transcription Factor NFATc4 and Development of New-Onset Diabetes After Transplantation in Hispanic Kidney Transplant Recipients
Transcription factors of the nuclear factor of activated T cells (NFAT) family regulate both immune activation and insulin production. Calcineurin inhibitors (CNIs) target NFAT activation. Hence, CNIs not only prevent organ transplant rejection but also contribute to the development of new-onset diabetes after transplantation (NODAT). Given individual variation in the susceptibility to NODAT, we hypothesized that polymorphisms in the cytoplasmic NFAT (NFATc)4 gene, which is expressed in pancreatic islets, may be associated with NODAT. Haplotype-tagging single-nucleotide polymorphisms (SNPs) of the NFATc4 gene were genotyped in Hispanic renal transplant patients. Cumulative incidences of NODAT were compared between recipients of different NFATc4 genotypes and haplotypes. The Cox proportional hazard model was used to examine risks for NODAT. Nongenetic and genetic characteristics were included in the multivariate risk model. The SNP (rs10141896) T allele was associated with a lower cumulative incidence of NODAT (P=0.02). This is a tagging SNP for one of the five dominant NFATc4 haplotypes, T-T-T-T-G, and CNI-treated recipients with this haplotype had a reduced adjusted risk for NODAT (hazard ratio: 0.45; 95% confidence interval: 0.19–1.01). Conversely, patients homozygous for the C-C-C-G-G haplotype were at an increased risk (hazard ratio: 2.13; 95% confidence interval: 1.01–4.46) for NODAT in subanalysis. Of the nongenetic factors, use of tacrolimus, sirolimus, and older age were associated with increased risk for NODAT. Polymorphisms in the NFATc4 gene may confer certain protection or predisposition for NODAT.
Date de mise en ligne : Mercredi 31 décembre 1969
Wagner, Doris; Amrein, Karin; Dimai, Hans Peter; Kniepeiss, Daniela; Tscheliessnigg, Karl Heinz; Kornprat, Peter; Dobnig, Harald; Pieber, Thomas; Fahrleitner-Pammer, Astrid
Ibandronate and Calcitriol Reduces Fracture Risk, Reverses Bone Loss, and Normalizes Bone Turnover After lTX
Background. Osteoporosis is a common complication in long-term survivors after liver transplantation (LTX). This study investigates the influence of a combination therapy of low dose parenteral ibandronate (IBN) and calcitriol on top of calcium and vitamin D supplementation in such patients.
Methods. For 3 years, 30 osteoporotic patients after LTX (28±6 months) were treated with quarterly 2 mg IBN intravenously and daily calcitriol (0.25–1.0 μg) on top of 1000 mg calcium and 800 IU vitamin D. Recipients with normal bone density (n=24) were enrolled as controls. Laboratory analysis and dual energy X-ray absorptiometry were performed at baseline and every 12 months. Primary endpoints were changes in bone mineral density and fracture incidence.
Results. IBN patients showed a significant increase of bone mineral density at the femoral neck and the trochanteric region (13% and 15%, respectively, both P=0.001) as compared with baseline whereas the control group revealed a small but significant loss of −5.0% in the trochanteric and −4.9% in the neck region (P<0.05) over the same time period. Fracture incidence was low among IBN patients (7%); however, 23% of the control patients sustained at least one vertebral fracture. The relative fracture risk was 3.21 for IBN patients (95% confidence interval, 0.6–20.9, P=0.03) resulting in an absolute risk reduction for a new vertebral fracture of 14%.
Conclusion. In LTX recipients with osteoporosis combination therapy with low dose IBN and calcitriol on top of calcium and vitamin D supplementation is an effective treatment option.
Date de mise en ligne : Mercredi 31 décembre 1969
Kovacs, Francisco M.; Abraira, VÃctor; Gérvas, Juan; Arana, Estanislao; Peul, Wilco C.; Schoene, Mark L.; Corbin, Terry P.
Overenthusiastic Interpretations of a Nonetheless Promising Study
No abstract available
Date de mise en ligne : Mercredi 31 décembre 1969
Orozco, Lluis; Soler, Robert; Morera, Carles; Alberca, Mercedes; Sánchez, Ana; GarcÃa-Sancho, Javier
Response to “Overenthusiastic Interpretations of a Nonetheless Promising Studyâ€: Facts and Opinions
No abstract available
Date de mise en ligne : Mercredi 31 décembre 1969
Moreau, François; Toti, Florence; Bayle, François; Berney, Thierry; Egelhofer, Harald; Chastre, Maxime; Richard, Marie Jeanne; Greget, Michel; Masson, Dominique; Zobairi, Fatiha; Benhamou, Pierre-Yves.; Kessler, Laurence
Rescue of a Pancreatic Islet Graft After Steroid Therapy
No abstract available
Date de mise en ligne : Mercredi 31 décembre 1969
Caballero, Francisco; Puig, Mireia; Santos, José Alberto; Deulofeu, Roser; BallarÃn, José; Charco, Ramón; Leal, Jesús
Successful Transplantation of Organs From a Donor With Postneurosurgical Meningitis Caused by Escherichia coli
No abstract available
Date de mise en ligne : Mercredi 31 décembre 1969
Cyclosporine A-Based Immunosuppression Reduces Relapse Rate After Antiviral Therapy in Transplanted Patients With Hepatitis C Virus Infection: A Large Multicenter Cohort Study: Erratum
No abstract available