Journal of Transplantation最新文献

Background: The role of protocol renal allograft biopsy in kidney transplantation is controversial due to the concern with procedural-related complications; however, its role is slowly evolving. Recent evidence suggests that protocol biopsy is useful in detecting subclinical renal pathology. Early recognition and treatment of renal pathologies can improve long-term outcomes of renal allografts.

Methodology: A total of 362 renal allograft protocol biopsies were performed in adult recipients of kidney transplantation between 2012 and 2017. After excluding those with poor quality or those performed with a baseline serum creatinine level >200 umol/L, we analyzed 334 (92.3%) biopsies. Histology reports were reviewed and categorized into histoimmunological and nonimmunological changes. The immunological changes were subcategorized into the following: (1) no acute rejection (NR), (2) borderline changes (BC), and (3) subclinical rejection (SCR). Nonimmunological changes were subcategorized into the following: (1) chronicity including interstitial fibrosis/tubular atrophy (IFTA), chronic T-cell-mediated rejection (TCMR), unspecified chronic lesions, and arterionephrosclerosis, (2) de novo glomerulopathy/recurrence of primary disease (RP), and (3) other clinically unsuspected lesions (acute pyelonephritis, calcineurin inhibitors toxicity, postinfective glomerulonephritis, and BK virus nephropathy). Risk factors associated with SCR were assessed.

Results: For the histoimmunological changes, 161 (48.2%) showed NR, 145 (43.4%) were BC, and 28 (8.4%) were SCR. These clinical events were more pronounced for the first 5 years; our data showed BC accounted for 59 (36.4%), 64 (54.2%), and 22 (40.7%) biopsies within <1 year, 1-5 years, and > 5 years, respectively (p = 0.011). Meanwhile, the incidence for SCR was 6 (3.7%) biopsies in <1 year, 18 (15.3%) in 1-5 years, and 4 (7.4%) in >5 years after transplantation (p=0.003). For the nonimmunological changes, chronicity, de novo glomerulopathy/RP, and other clinically unsuspected lesions were seen in 40 (12%), 10 (3%), and 12 (3.6%) biopsies, respectively. Living-related donor recipients were associated with decreased SCR (p=0.007).

Conclusions: Despite having a stable renal function, our transplant recipients had a significant number of subclinical rejection on renal allograft biopsies.

Identification of patients at risk of kidney graft loss relies on early individual prediction of graft failure. Data from 616 kidney transplant recipients with a follow-up of at least one year were retrospectively studied. A joint latent class model investigating the impact of serum creatinine (Scr) time-trajectories and onset of de novo donor-specific anti-HLA antibody (dnDSA) on graft survival was developed. The capacity of the model to calculate individual predicted probabilities of graft failure over time was evaluated in 80 independent patients. The model classified the patients in three latent classes with significantly different Scr time profiles and different graft survivals. Donor age contributed to explaining latent class membership. In addition to the SCr classes, the other variables retained in the survival model were proteinuria measured one-year after transplantation (HR=2.4, p=0.01), pretransplant non-donor-specific antibodies (HR=3.3, p<0.001), and dnDSA in patient who experienced acute rejection (HR=15.9, p=0.02). In the validation dataset, individual predictions of graft failure risk provided good predictive performances (sensitivity, specificity, and overall accuracy of graft failure prediction at ten years were 77.7%, 95.8%, and 85%, resp.) for the 60 patients who had not developed dnDSA. For patients with dnDSA individual risk of graft failure was not predicted with a so good performance.

Introduction. The possible risk factors for chronic kidney disease in transplant recipients have not been thoroughly investigated after living-donor liver transplantation. Material and Methods. A retrospective cohort study of consecutive adults who underwent living-donor liver transplantation between May 2004 and October 2016, in a single center, was conducted. Kidney function was investigated successively for all the patients throughout the study period, with 12 months being the shortest follow-up. Postoperative renal dysfunction was defined in accordance with the Chronic Kidney Disease Epidemiology Collaboration criteria. The patients' demographic data, preoperative and intraoperative parameters, and outcomes were recorded. A calcineurin inhibitor-based immunosuppressive regimen, either tacrolimus or cyclosporine, was used in all the patients. Results. Of the 413 patients included in the study, 33 (8%) who survived for ≥1 year experienced chronic kidney disease 1 year after living-donor liver transplantation. Twenty-seven variables were studied to compare between the patients with normal kidney functions and those who developed chronic kidney disease 1 year after living-donor liver transplantation. Univariate regression analysis for predicting the likelihood of chronic kidney disease at 1 year revealed that the following 4 variables were significant: operative time, P < 0.0005; intraoperative blood loss, P < 0.0005; preoperative renal impairment, P = 0.001; and graft-to-recipient weight ratio (as a negative predictor), P < 0.0005. In the multivariate regression analysis, only 2 variables remained as independent predictors of chronic kidney disease at 1 year, namely, operative time with a cutoff value of ≥714 minutes and graft-to-recipient weight ratio as a negative predictor with a cutoff value of <0.91. Conclusion. In this study, prolonged operative time and small graft-to-recipient weight ratio were independent predictors of chronic kidney disease at 1 year after living-donor liver transplantation.

Background: Recent changes in the demographic of cardiac donors and recipients have modulated the rate and risk, associated with posttransplant diabetes mellitus (PTDM). We investigated the secular trends of the risk of PTDM at 1 year and 3 years after transplantation over 30 years and explored its effect on major outcomes.

Methods: Three hundred and three nondiabetic patients were followed for a minimum of 36 months, after a first cardiac transplantation performed between 1983 and 2011. Based on the year of their transplantation, the patients were divided into 3 eras: (1983-1992 [era 1], 1993-2002 [era 2], and 2003-2011 [era 3]).

Results: In eras 1, 2, and 3, the proportions of patients with PTDM at 1 versus 3 years were 23% versus 39%, 21% versus 26%, and 33% versus 38%, respectively. Independent risk factors predicting PTDM at one year were recipient's age, duration of cold ischemic time, treatment with furosemide, and tacrolimus. There was a trend for overall survival being worse for patients with PTDM in comparison to patients without PTDM (p = 0.08). Patients with PTDM exhibited a significantly higher rate of renal failure over a median follow-up of 10 years (p = 0.03).

Conclusion: The development of PTDM following cardiac transplantation approaches 40% at 3 years and has not significantly changed over thirty years. The presence of PTDM is weakly associated with an increased mortality and is significantly associated with a worsening in renal function long-term following cardiac transplantation.

Survivin, an antiapoptotic molecule from inhibitor of apoptosis protein (IAP) family, is most known for its implication in cancer as there are some efforts to apply it for diagnostic as well as therapeutic purposes in oncology. On the other hand, it could be a useful molecule to be positively targeted when trying to save tissue and promote cells viability. Since protecting the allograft from ischemia reperfusion injury and inflammation-induced damage is a considerable objective in transplantation, it is reasonable to take advantage from antiapoptotic agents like survivin in order to achieve this goal. However, survivin's potential ability to induce malignancies makes some concerns about its use in clinic. The other barrier is this molecule's involvement in lymphocytes development and proliferation which might increase the risk of graft rejection due to adaptive immune system overactivation. In this review we summarize the few studies carried out about survivin's effect on graft survival and probable advantages and disadvantages of its overexpression in transplantation.

Objective: Organ transplant recipients receive immunosuppressive regimens to prevent transplant rejection, which put them at increased risk for opportunistic infections like cytomegalovirus (CMV). Ganciclovir and Valganciclovir are mostly used to prevent or treat CMV. Any incorrect use of the drug may have serious consequences for patients. In this study, the outcome of transplant recipients was assessed in relation to the optimal or suboptimal use of Ganciclovir or Valganciclovir.

Methods: This study was performed on 148 hospitalized patients who received Ganciclovir or Valganciclovir in the nephrology and kidney transplantation departments of our university hospitals, from March 2012 to December 2016. Patients' demographic and clinical data including dose and duration of treatment were collected and then analyzed in comparison with the standard CMV treatment protocols.

Findings: About 94.6% of patients received Ganciclovir or Valganciclovir therapy consistent with the standard defined indications. The mean ratio of prescribed daily dose to the optimal dose was 2.9 in the first dose, 2.0 in the second dose, 1.3 in the third dose, and 1.5 in the fourth dose. From 148 included patients, 26.5% experienced CMV infection once, 7.2% experienced CMV infection twice, and 1.2% had CMV infection for 3 times, within six-month follow-up after first episode of antiviral therapy during hospitalization.

Conclusion: In this study, empiric anti-CMV therapy was initially given. The doses used were generally higher than recommended but we could not find more adverse events in the patients receiving high initial doses. In any case, it seems necessary to advocate use of standard treatment guidelines to avoid adverse outcomes.

Background: Near infrared light (NIR) fluorescence imaging with indocyanine green (ICG) has been used in various aspects of surgery, such as in the assessment of vascular anastomosis, tissue perfusion, and the identification of lymph nodes. In this study we evaluated the utility of NIR/ICG fluorescence imaging in kidney transplantation.

Materials and methods: NIR/ICG imaging was used to assess allograft perfusion in n=1 living donor (LDRT) and n=2 deceased donor (DDRT) renal transplantations, performed in February 2017. The allograft arterial and venous anastomoses were done end-to-side to the corresponding recipient external iliacs, and ureteroneocystostomies were performed for urinary reconstructions. After completion of vascular anastomosis, ICG was given as intravenous bolus at 0.3mg/kg, followed by visual assessment of tissue perfusion and vascular anastomoses at 1-minute interval using fluorescence imaging (KARL STORZ NIR/ICG System).

Results: Homogenous global fluorescence of the allograft and vascular anastomosis was observed in all 3 cases. Immediate postoperative perfusion studies showed patent inflow and outflow vessels and well perfused transplanted kidneys. Immediate graft function was observed in 2 recipients (1 LDRT and 1 DDRT). One session of haemodialysis was performed in 1 DDRT recipient, for high serum potassium in the immediate postoperative setting, who otherwise had good urine output and serially declining serum creatinine.

Conclusions: NIR/ICG fluorescence imaging can be useful in renal transplantation for the intraoperative assessment of allograft perfusion, especially in complex cases with multiple renal arteries and vascular reconstructions.

The scope and application of hematopoietic stem cell transplantation are increasing. With advancement in science and close cooperation of health centers, HSCT units are coming up in new developing and underdeveloped countries. India hosts many HSCT units and often provides financially viable option for HSCT to foreign patients as well. Recently Indian Council of Medical Research (ICMR) issued a guideline about HSCT unit in India. This review article discusses establishment of new HSCT unit in resource limited setting. Subsequent implication of ICMR guideline has been done.

Drug-induced hematological cytopenia is common in kidney transplantation. Various cytopenia including leucopenia (neutropenia), thrombocytopenia, and anemia can occur in kidney transplant recipients. Persistent severe leucopenia or neutropenia can lead to opportunistic infections of various etiologies. On the contrary, reducing or stopping immunosuppressive medications in these events can provoke a rejection. Transplant clinicians are often faced with the delicate dilemma of balancing cytopenia and rejection from adjustments of immunosuppressive regimen. Differentials of drug-induced cytopenia are wide. Identification of culprit medication and subsequent modification is also challenging. In this review, we will discuss individual drug implicated in causing cytopenia and correlate it with corresponding literature evidence.

Delayed graft function (DGF) increases the risk of graft loss by up to 40%, and recent developments in kidney donation have increased the risk of its occurrence. Lowering the risk of DGF, however, is challenging due to a complicated etiology in which ischemia-reperfusion injury (IRI) leads to acute tubular necrosis. Among various strategies explored, the choice of induction therapy is one consideration. Rabbit antithymocyte globulin (rATG [Thymoglobuline]) has complex immunomodulatory effects that are relevant to DGF. In addition to a rapid and profound T-cell depletion, rATG inhibits leukocyte migration and adhesion. Experimental studies of rATG have demonstrated attenuated IRI-related tissue damage in reperfused tissues, consistent with histological evidence from transplant recipients. Starting rATG intraoperatively instead of postoperatively can improve kidney graft function and reduce the incidence of DGF. rATG is effective in preventing acute rejection in kidney transplant recipients at high immunological risk, supporting delayed calcineurin inhibitor (CNI) introduction which protects the graft from early insults. A reduced rate of DGF has been reported with rATG (started intraoperatively) and delayed CNI therapy compared to IL-2RA induction with immediate CNI in patients at high immunological risk, but not in lower-risk patients. Overall, induction with rATG induction is the preferred choice for supporting delayed introduction of CNI therapy to avoid DGF in high-risk patients but shows no benefit versus IL-2RA in lower-risk individuals. Evidence is growing that intraoperative rATG ameliorates IRI, and it seems reasonable to routinely start rATG before reperfusion.