The findings presented here demonstrate the potential of studying DNA methylation of the T cells to identify kidney transplantpatients at risk for de novo post-transplant cSCC . We showed that there were systemic differences between future cSCC and non- cSCC patients prior to transplantation. A longitudinal analysis showed that several DNA methylation profiles remained relatively stable after transplantation, suggest- ing a lasting effect on the development of de novo cSCC after transplantation. In the future, identification of pa- tients at increased risk for post-transplant cSCC before transplantation will allow for early clinical interventions such as regular visits to the dermatologist and stricter lifestyle advice to the patient to minimize additional sun exposure . Ultimately, it may lead to adjustment of the immunosuppressive load but this remains a fine bal- ance between reducing the risk for cancer and causing irreversible damage to the allograft.
Although lymphocyte dysfunction has been observed in a few such patients, no systematic study of neutrophil function has yet been reported. Neutrophil chemotaxis was evaluated by a 51Cr-radioassay after bone marrow transplantation in 34 patients with acute leukemia or aplastic anemia. The response to a chemotactic stimulus (C5a) was severely depressed (less than 35% of normal) in 18 patients, moderately depressed (35-65% of normal) in an additional 6, and normal in 10 subjects. The mean response in the absence of graft vs. host disease and antithymocyte globulin administration was 73.3+/-9.2% (SE) in contrast to 29.7+/-9.6% (P is less than 0.01) in patients with graft vs. host disease treated with antithymocyte golbulin. Both graft vs. host disease and antithymocyte globulin were implicated since the presence of either factor alone was associated with depressed chemotaxis (31.1+/-4.9% for graft vs. host disease, P is less than 0.01; 17.0+/-7.8% for antithymocyte globulin, P is less than 0.02). When normal neutrophils were incubated with antithymocyte globulin in vitro, their chemotactic response was markedly suppressed in the absence of a cytotoxic effect. Transplantpatients with defective chemotaxis experienced significantly more infections than those with normal chemotaxis, and analysis of specific etiologic agents showed that this was predominantly related to bacterial pathogens. Chemotactic inhibitors […]
Tacrolimus, also known as FK506 or Prograf, is a macrolide compound that was isolated by Fujisawa researchers from the culture broth of a soil microorganism Streptomyces tsukubaensis near Mount Tsukuba, Japan in 1984, the marked immunosuppressive properties of tacrolimus were confirmed following extensive in vitro and in vivo testing , thereby identifying what would become a cornerstone of immunosuppressive prophylaxis after solid organ transplantation. Tacrolimus was first launched in Japan in 1993, for prevention of allograft rejection in liver or kidney transplantpatients. In the US, tacrolimus (Prograf) was approved for prevention of rejection in liver transplant recipients in 1994, and in kidney transplant recipients in 1997. In 2003, tacrolimus was used as initial immunosuppression in 67% of kidney recipients and 89% of liver recipients
The tendency to resort to transplant tourism among these end stage kidney transplantpatients as reported in this study could have accrued from paucity of transplant centers in Nigeria and overwhelming ignorance in the population. Thus the need for government, industries and other non-governmental organizations to invest in the development of ad- equate health facilities to cater for the health need of the populace including management of patients with renal diseases. Policy makers should regulate treat- ment abroad and limit it to only for those treatments not available in the country. There should be massive awareness campaign to encourage altruistic kidney donation and discourage commercial organ donation. Public focused governance to improve the well being and economic state of the populace, as this will reduce the frequency of organ sale. In Iran, a realistic and community acceptable policy was developed in order to regulate living kidney donation; however appropriate application of this policy in developing countries is questionable .
Infection in the early post-transplant period (<1 month) is most commonly bacterial and are primarily nosocomial such as enterococci, staphylococci, gram-negative aerobes, anaerobes or candida species. They are most commonly intra-abdominal (cholangitis, liver, and other abdominal abscesses) and are observed during the post-transplant hospitalization. Infected transplantpatients may present with fever, abdominal pain or jaundice or they may be possibly asymptomatic because of immunosuppression. A complete blood investigation, liver function tests, renal function test, coagulation profile, urine analysis were done. Symptomatic investigations are done for culture. Further investigations may include radiological investigations, abdominal ultrasonography,
Abstract: Psychological assessments are crucial for the evaluation and optimization of the suitability of transplantpatients. The interdisciplinary evaluation in modern transplantation medicine focuses on important psychosocial issues, such as assessing patients’ characteristics that predict best postoperative outcome after solid organ transplantation. When assessing patients for reconstructive hand transplantation, the psychological evaluation should identify whether reconstructive hand transplantation is the best treatment option to regain functionality and sensation, to resolve body image concerns, and to improve health-related quality of life (HRQOL) for each patient. These psychosocial issues in transplantation medicine are receiving increased attention; however, standardized psychological evaluation and follow-up protocols are still being developed. Previously published reports in transplantation medicine have attempted to identify psychosocial factors important in the evaluation of transplantpatients and that predict psychosocial outcomes. This review will provide an overview of recent investigations in solid organ and vascularized composite allotransplantation (VCA), including the domains of evaluation, pre- and posttransplant follow-up, psychiatric complications, evaluation of body image, and HRQOL. Recent work highlights the potential for a multicenter research approach utilizing standardized assessment strategies and emphasizing the need for a shared assessment approach to understand psychosocial outcomes. For example, the Chauvet Workgroup convened in 2014 in Paris with stakeholders in the assessment of psychosocial factors to discuss key areas and propose an ongoing shared effort across centers in addressing important questions related to psychosocial care of VCA. A successful transplantation requires a multistaged multidisci- plinary psychosocial evaluation to identify those most suited to solid organ or reconstructive transplantation and minimize psychological morbidity. With this in place, current transplant psychosocial practices can be useful for solid organ transplantation and refined for VCA. This review will present potential challenges and solutions for guideline development in both solid organ and VCA.
basiliximab, all patients were treated with CsA, EC-MPS and corticosteroids for the first 4.5 months post-transplantation. Subsequently, patients were randomized 1:1 to either continue the current regimen of CsA and EC-MPS or to convert from CsA to everolimus. The primary objective of this trial was to show superiority of a CNI-free regimen with respect to the renal function at Month 12 post transplant assessed by GFR (Nankivell method) compared with the standard CNI-based regimen. The results have recently been submitted for publication.
Among long-term transplant recipients, there is limited information regarding the association of anemia with adverse cardiovascular events. In a retrospective study of 638 transplant recipients between 1969 and 1999 who were alive and free of cardiac disease 1 year after transplantation, lower Hb levels were associated with an increased risk for de novo Congestive heart failure (RR, 1.24/10-g/dL decrease in Hb; 95% CI, 1.10 to 1.39; P = 0.001). In a follow-up study, anemia was associated with increase in left ventricular mass (as measured by Cornell voltage on electrocardiogram) during the first 5 years after transplantation.
In patients with renal insufficiency, dosage modifications are necessary for agents that are excreted mainly by the kidneys. In renal failure, the kidney may not be able to concentrate an antimicrobial agent in the urine and difficulty in eradicating bacteriuria may occur. This could be an important factor in failure of therapy for UTI with aminoglycosides. In addition, high concentrations of magnesium and calcium as well as low pH level can raise the MIC of aminoglycosides for Gram negative bacilli to levels above those achievable in the urine of patients with renal failure (121). In general, penicillins and cephalosporins attain adequate urine concentrations despite severly impaired renal function and are the agents of choice in renal insufficiency (34), and probably also in renal transplant.
Belatacept is the most recently introduced immunosuppres- sive drug. It is a fusion protein between a genetically modi- fied CD152 (CTLA4) domain and a human immunoglobulin G domain. It blocks costimulation of T-lymphocytes via the CD28 pathway and requires intravenous administration, more frequently during the early period after transplanta- tion and then monthly. When compared to cyclosporin, acute rejection rates were higher but there was less chronic damage on protocol biopsies. An increased incidence of posttransplant lymphoproliferative disorder in Epstein–Barr virus naïve patients is an important concern. The phar- macokinetics of belatacept are predictable with limited variation between individuals, unlike the small molecule immunosuppressive drugs. 35
transplantation. Graft atherosclerosis is typically diffuse and difficult to detect even with coronary arteriography. Recently, acetylcholine was shown to dilate blood vessels by releasing a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). We have demonstrated paradoxical vasoconstriction induced by acetylcholine both early and late in the course of coronary atherosclerosis in patients, suggesting an
total hip replacements in renal transplantpatients for a mean duration of 3.1 years and found that none of the hips had to be revised. They concluded that the early results of porous-coated implants were satisfactory. During the last decade, the number of short-stem arthroplasties is increasing, although there are no reports on the outcome of short-stem arthroplasties in patients with ONFH. One study reports the use of a metaphyseal-fitting anatomic cementless femoral component in 84 total hip replace- ments in patients with a mean age of 78.9 (range 70–88) years. The mean follow-up duration was 4.6 (4–5) years. The mean preoperative Harris hip score was 26 (0–56), which improved to 89 (61–100) at the final follow-up. No patient had thigh pain. Osseointegration was seen in all femoral and acetabular components. All hips had grade 1 stress shielding of the proximal femur. No acetabular or femoral osteolysis was identified. 109
In general, molecular quantitative CMV tests provide earlier detection of CMV viremia than pp65 antigenemia tests, although the increased sensitivity may result in unnecessary prolonged therapy and increased toxicity. Quantitative assays used in the laboratory for measuring CMV viremia have a significant impact on the clinical management of transplantpatients. Since institu- tional guidelines for initiating therapy rely on specific numerical values generated by the laboratory, a clear understanding of the test performance characteristics, including the specimen type used, the limit of detection, the limit of quantification, the linear range, and the reproducibility of the assay, is necessary for an accurate interpretation of the CMV viral loads. Studies have shown that CMV viral loads measured in whole blood are gener- ally higher than those measured in plasma, as whole blood may contain both free and cell-associated CMV virions. Viral loads in whole blood may therefore overestimate the level of actively rep- licating viruses (27). Until recently, standardization of the many laboratory-developed quantitative CMV tests was not feasible. The recent availability of the World Health Organization (WHO) international CMV standards and the introduction of commercial in vitro diagnostic (IVD)-cleared assays should result in improved standardization of CMV viral loads obtained from different insti- tutions.
Abstract: Successful management of the solid-organ transplant recipient begins with prevention of rejection and achieving a balance between insufficient and excessive immunosuppression. Standard tacrolimus therapy for prevention of solid-organ transplant rejection consists of 2 divided doses per day. In an effort to simplify tacrolimus dosing to once daily, a new formulation (tacroli- mus prolonged release [PR]) was chosen for its combination of a similar extent of bioavailability and a substantially reduced rate of clearance. Several clinical conversion studies have now been completed using PR to clarify its pharmacokinetics, efficacy at prevention of allograft rejection, and safety profiles in solid-organ transplantpatients. A cohort of 67 stable kidney transplant recipients was converted from standard tacrolimus to PR in an open-label, multicenter study in the United States and Canada. A second open-label, multicenter study was performed in liver transplant recipients with stable graft function on standard tacrolimus therapy converted to PR. A third conversion study was performed as an open-label study at 5 centers in the United States in stable pediatric liver transplant recipients. As medication noncompliance can significantly contribute to the incidence of graft rejection and graft loss in transplant recipients, a potentially significant advance in the transplant community’s ongoing mission to optimize prevention of rejection occurred with the development of a once-daily tacrolimus PR. The results of these preliminary studies suggest that select solid-organ transplant recipients converted to PR can be safely maintained using the same monitoring and patient care techniques historically used for standard tacrolimus therapy.
The differential diagnosis of lung transplantpatients with declining allograft function weeks to months after transplant includes acute rejection, infection, airway complications (air- way stenosis, tracheobronchomalacia, or granulation tissue), vascular anastomotic complications, chronic rejection, and cardiac dysfunction [4, 22]. Evaluation includes a battery of laboratory testing for evidence of infection, imaging with chest radiography or CT, spirometry, and flexible bronchos- copy for bronchoalveolar lavage and transbronchial biopsy to confirm the diagnosis of acute rejection and to exclude processes such as infection, aspiration or organizing pneu- monia [4, 22]. Even after a thorough evaluation, some cases can prove diagnostically challenging. The evaluation of these patients can be greatly complicated by presence of more than one process in the same patient (Fig. 6). Post- transplant lymphoproliferative disorder could rarely present early during the first weeks post lung transplant and should be considered in the differential diagnosis of persistent opacities during this period .
Post-transplant diabetes mellitus (PTDM), developing in almost one quarter of renal transplantpatients within three years after the procedure, contributes to post-transplant morbidity and mortality by increasing the risk of infection and cardiovascular events. PTDM is considered a variant of diabetes mellitus (DM) type II and results in similar microvascular and macrovascular diabetic complications seen in non-transplantpatients. In this article, we present a case of single lung transplant patient who developed PTDM with a severe DKA as the first manifestation of the disease. PTDM resolved rapidly after discontinuing tacrolimus. (Tanaffos 2009; 8(4): 55-59)
For PAH patients who survive the early post-transplant period, long-term outcomes are good and are frequently better than for many other indications. Data from the ISHLT registry have demonstrated that for primary transplantpatients with IPAH who survived to 1 year, conditional median survival was 10.0 years. In contrast, conditional median survival for patients with chronic obstructive pulmonary disease or interstitial lung disease was only 7.0 and 6.9 years, respectively . Although the early post-operative period is clearly the time of greatest risk, lung transplant recipients are frequently affected by a number of serious long-term complications, including bronchiolitis obliterans syndrome (BOS), malignancies and infection . According to the ISHLT registry, almost half (41.5%) of all lung transplant survivors develop BOS within 5 years of transplant  and it remains a leading cause of death in the long-term, accounting for 21.5% of all deaths that occur more than 10 years post-transplant . A similar proportion of deaths in IPAH patients that occur more than 10 years post-transplant are attributable to BOS (21.7%) . Other long-term complications affecting transplantpatients include systemic hypertension, hyperlipidaemia, renal dysfunction and diabetes, all of which occur commonly as a consequence of immunosuppression therapies .
An increasing number of failed transplantpatients returning to dialysis (FTRD) have been ob- served with reported worse survival compared to transplant-naive dialysis (TxN) patients. This study aimed to assess outcomes of FTRD vs. matched TxN controls in a Gulf region multi-center trial of 800 HD patients. Similar mortality was seen, likely due to earlier start and better HD ade- quacy in FTRD. Younger age, less diabetes and living donor transplantation in majority with 27% graft nephrectomy (Nx) might also confer benefits. Subgroup analysis of Nx patients showed more hospitalizations and prior rejection episodes with lower graft survival. The deaths, however, oc- curred only in nonNx group and are likely explained by older age, longer duration on HD, more prevalence of diabetes and CAD. FTRD showed similar survival to TxN. Early intensive HD might account for the benefit. Whether Nx confers advantage is unclear because of the small sample size.
Background: Diabetes is a disease of increasing worldwide prevalence and is the main cause of chronic renal failure. Type 1 diabetic patients with chronic renal failure have the following therapy options: kidney transplant from a living donor, pancreas after kidney transplant, simultaneous pancreas-kidney transplant, or awaiting a deceased donor kidney transplant. For type 2 diabetic patients, only kidney transplant from deceased or living donors are recommended. Patient survival after kidney transplant has been improving for all age ranges in comparison to the dialysis therapy. The main causes of mortality after transplant are cardiovascular and cerebrovascular events, infections and neoplasias. Five-year patient survival for type 2 diabetic patients is lower than the non-diabetics' because they are older and have higher body mass index on the occasion of the transplant and both pre- and posttransplant cardiovascular diseases prevalences. The increased postransplant cardiovascular mortality in these patients is attributed to the presence of well-known risk factors, such as insulin resistance, higher triglycerides values, lower HDL-cholesterol values, abnormalities in fibrinolysis and coagulation and endothelial dysfunction. In type 1 diabetic patients, simultaneous pancreas-kidney transplant is associated with lower prevalence of vascular diseases, including acute myocardial infarction, stroke and amputation in comparison to isolated kidney transplant and dialysis therapy.
About 50% of people living with the HIV infection in Italy are co-infected with HCV. In this group of patients, the pri- mary cause of mortality is liver disease, which accounts for up to 14% of deaths. HIV/HCV co-infection also exposes patients to a higher risk of progression to AIDS, a faster evolution towards cirrhosis, more frequent drug toxicity, and lower tolerance for antiretroviral therapy. Moreover, HCV infection can play a part in increasing immune system de- pression; neurological, cognitive and renal damage; and bone fragility. Hence an optimal antiretroviral regimen needs to be chosen for co-administration with anti-HCV therapy and timed appropriately to improve the prognosis of co-infected HIV/HCV patients. Unfortunately, however, data on the safety and efficacy of antiretroviral drugs in these patients is scarce, as are studies of pharmacokinetics in patients with advanced liver impairment. Furthermore, restoring adequate immune constitution seems not to slow the progression of liver disease, and the metabolic and hepatic toxicity of some antiretroviral drugs can even contribute to inflammatory and fibrogenic processes. It is therefore essential that HIV/ HCV co-infected patients receive only medications capable of ensuring the best immune recovery but possessing the lowest potential to trigger immune reconstitution syndrome or hepatic and metabolic damage.