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Clinical Reviews in Allergy & Immunology Feb 2017Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy (IIMs) and... (Review)
Review
Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy (IIMs) and myositis-associated ILD (MA-ILD). Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. As treatment of refractory cases of idiopathic inflammatory myopathies has been challenging, there is growing interest in evaluating newer therapies including biologics that target various pathways involved in the pathogenesis of IIMs. In a large clinical trial of rituximab in adult and juvenile myositis, the primary outcome was not met, but the definition of improvement was met by most of this refractory group of myositis patients. Rituximab use was also associated with a significant glucocorticoid-sparing effect. Intravenous immune globulin (IVIg) can be used for refractory IIMs or those with severe dysphagia or concomitant infections. Anti-tumor necrosis factor (anti-TNF) utility in IIMs is generally limited by previous negative studies along with recent reports suggesting their potential for inducing myositis. Further research is required to assess the role of new therapies such as tocilizumab (anti-IL6), ACTH gel, sifalimumab (anti-IFNα), and abatacept (inhibition of T cell co-stimulation) given their biological plausibility and encouraging small case series results. Other potential novel therapies include alemtuzumab (a humanized monoclonal antibody which binds CD52 on B and T lymphocytes), fingolimod (a sphingosine 1-phosphate receptor modulator that traps T lymphocytes in the lymphoid organs), eculizumab, and basiliximab. The future investigations in IIMs will depend on well-designed controlled clinical trials using validated consensus core set measures and improvements in myositis classification schemes based on serologic and histopathologic features.
Topics: Biological Factors; Humans; Immunosuppressive Agents; Myositis
PubMed: 26767526
DOI: 10.1007/s12016-016-8530-2 -
Emerging Infectious Diseases Nov 2022A multispecies outbreak of Nocardia occurred among heart transplant recipients (HTR), but not lung transplant recipients (LTR), in Sydney, New South Wales, Australia,... (Review)
Review
A multispecies outbreak of Nocardia occurred among heart transplant recipients (HTR), but not lung transplant recipients (LTR), in Sydney, New South Wales, Australia, during 2018-2019. We performed a retrospective review of 23 HTR and LTR who had Nocardia spp. infections during June 2015-March 2021, compared risk factors for Nocardia infection, and evaluated climate conditions before, during, and after the period of the 2018-2019 outbreak. Compared with LTR, HTR had a shorter median time from transplant to Nocardia diagnosis, higher prevalence of diabetes, greater use of induction immunosuppression with basiliximab, and increased rates of cellular rejection before Nocardia diagnosis. During the outbreak, Sydney experienced the lowest monthly precipitation and driest surface levels compared with time periods directly before and after the outbreak. Increased immunosuppression of HTR compared with LTR, coupled with extreme weather conditions during 2018-2019, may explain this outbreak of Nocardia infections in HTR.
Topics: Humans; Basiliximab; Trimethoprim, Sulfamethoxazole Drug Combination; Nocardia Infections; Nocardia; Transplant Recipients; Disease Outbreaks; Heart Transplantation
PubMed: 36287030
DOI: 10.3201/eid2811.220262 -
Journal of Medicine and Life Jan 2022Renal transplant patients show a high prevalence of cytomegalovirus (CMV) infection after the procedure. This study was conducted to assess the prevalence and factors...
Renal transplant patients show a high prevalence of cytomegalovirus (CMV) infection after the procedure. This study was conducted to assess the prevalence and factors associated with the incidence of CMV infection among renal transplant patients. A total of 100 patients were recruited in this study. The CMV load in the blood of each patient was assessed using the technique of polymerase chain reaction (PCR). The serostatus of all recipients and donors was examined preoperatively and those of the recipients again postoperatively. The association of CMV load was assessed with the following factors: age, gender, alanine aminotransferase (ALT) and serum creatinine levels, types of immunosuppressive and induction regimens, preoperative diabetes status, and serological virologic response (SVR) at 12 weeks postoperatively. Our findings showed that CMV incidence was significantly higher in middle-aged patients (62 of 66 patients, 93.9%; p=0.0001). Furthermore, about 88.2% of patients induced by anti-thymocyte globulin (ATG) showed a high viral load, significantly higher than the proportion of CMV-positive patients induced by basiliximab (p=0.001). In addition, a higher proportion of CMV-negative recipients who received the graft from CMV-positive donors and vice-versa were CMV-positive postoperatively. Administration of Valcyte 450 showed 100% efficiency in decreasing the CMV load in the patients. Among all the assessed factors, only the age of the recipients, type of induction therapy used, and the preoperative serostatus of both donors and recipients were significantly associated with the postoperative CMV incidence among the patients.
Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Graft Rejection; Humans; Immunosuppressive Agents; Infant; Kidney Transplantation; Middle Aged; Retrospective Studies
PubMed: 35186139
DOI: 10.25122/jml-2021-0209 -
Experimental and Clinical... Sep 2021Deceased donor renal transplant is an accepted treatment for patients with end-stage renal disease. We retrospectively analyzed urological and surgical complications and...
OBJECTIVES
Deceased donor renal transplant is an accepted treatment for patients with end-stage renal disease. We retrospectively analyzed urological and surgical complications and outcomes in our series.
MATERIALS AND METHODS
Since 2016, we have performed 263 renal transplants at the Gazi University Transplantation Center, Ankara, and 92 of these were from deceased donors. We retrospectively analyzed outcomes of these 92 deceased donor transplants from our database records. There were 45 female and 47 male recipients, and 20 were pediatric recipients. Mean recipient and donor ages were 36 ± 14 and 38 ± 18 years old, respectively. Immunosuppression therapy consisted of steroids, mycophenolate, and calcineurin inhibitors. Induction therapy was 20 mg basiliximab (Simulect) on day 0 and day 4. Antithymocyte globulin (2 mg∕kg) was used in steroid-resistant acute rejection cases.
RESULTS
There were 13 surgical complications (14.1%) after 92 consecutive deceased donor renal transplants, and 4 of these were classified as miscellaneous surgical complications. Four of 9 cases were early, and the rest were classified as late complications. Postoperative early complications were bleeding (n = 2), urine leak (n = 1), and renal artery thrombosis (n = 1). Lymphoceles (n = 4) and urine leak (n = 1) occurred as late complications. Postoperative median follow-up was 78 months, during which 11 grafts (12%) were lost and 7 patients (7.6%) died from sepsis (n = 4), myocardial infarction, aortic dissection, and fungal pneumonia. No patients died from any surgical complications. The 1-year, 5-year, and 10-year survival rates of patients were 98%, 94%, and 94% and for grafts were 97%, 94%, and 88%, respectively.
CONCLUSION
Despite the limited number of deceased donor organs, improvements of surgical techniques at our center have facilitated success with deceased donor renal transplant at rates similar to other successful centers in the world.
Topics: Basiliximab; Child; Female; Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Male; Postoperative Complications; Retrospective Studies; Steroids; Tissue Donors; Treatment Outcome
PubMed: 34085914
DOI: 10.6002/ect.2020.0554 -
Kidney Research and Clinical Practice Jan 2023Generally, an induction agent is chosen based on the conditions of the deceased donor and the recipient. Antithymocyte globulin (ATG) is preferred in relatively...
BACKGROUND
Generally, an induction agent is chosen based on the conditions of the deceased donor and the recipient. Antithymocyte globulin (ATG) is preferred in relatively high-risk conditions. No clear evidence indicates which induction agent is safer or more efficient for deceased donor kidney transplantation (DDKT). This study compares the efficacy and safety of basiliximab (BSX) and ATG according to donor characteristics in DDKT.
METHODS
A total of 724 kidney transplant recipients from three transplant centers were enrolled, and propensity score matching was performed. Based on a donor age of 60 years, donor kidney with acute kidney injury (AKI), and Kidney Donor Profile Index (KDPI) score of 65%, we investigated how the choice of induction therapy agent affected the posttransplant clinical outcomes of delayed graft function (DGF), acute rejection (AR), infectious complications, and allograft and patient survival.
RESULTS
AR and DGF did not differ significantly according to induction agent in elderly/young donor, AKI/non-AKI, and high-KDPI/ low-KDPI subgroups. The infection rate did not show meaningful differences. The differences in death-censored allograft survival and patient survival rates between induction agents were not statistically significant.
CONCLUSION
Our study suggests that BSX can produce clinical outcomes similarly favorable to those of ATG even in DDKT cases with relatively poor donor conditions. Nonetheless, the donor and recipient conditions, immunological risk, and infection risk must be all taken into consideration when choosing an induction agent. Therefore, clinicians should carefully select the induction therapy agent for DDKT based on the risks and benefits in each DDKT case.
PubMed: 36747359
DOI: 10.23876/j.krcp.21.159 -
Clinical Kidney Journal Nov 2022Coronavirus disease 2019 (COVID-19) in kidney transplant recipients has a high risk of complications and mortality, especially in older recipients diagnosed during the...
Coronavirus disease 2019 (COVID-19) in kidney transplant recipients has a high risk of complications and mortality, especially in older recipients diagnosed during the early period after transplantation. Management of immunosuppression has been challenging during the pandemic. We investigated the impact of induction immunosuppression, either basiliximab or thymoglobulin, on the clinical evolution of kidney transplant recipients developing COVID-19 during the early period after transplantation. We included kidney transplant recipients with ˂6 months with a functioning graft diagnosed with COVID-19 from the initial pandemic outbreak (March 2020) until 31 July 2021 from different Spanish centres participating in a nationwide registry. A total of 127 patients from 17 Spanish centres developed COVID-19 during the first 6 months after transplantation; 73 (57.5%) received basiliximab and 54 (42.5%) thymoglobulin. Demographics were not different between groups but patients receiving thymoglobulin were more sensitized [calculated panel reactive antibodies (cPRAs) 32.7 ± 40.8% versus 5.6 ± 18.5%] and were more frequently retransplants (30% versus 4%). Recipients ˃65 years of age treated with thymoglobulin showed the highest rate of acute respiratory distress syndrome [64.7% versus 37.1% for older recipients receiving thymoglobulin and basiliximab ( < .05), respectively, and 23.7% and 18.9% for young recipients receiving basiliximab and thymoglobulin ( > .05)], respectively, and the poorest survival [mortality rate 64.7% and 42.9% for older recipients treated with thymoglobulin and basiliximab, respectively ( < .05) and 8.1% and 10.5% for young recipients treated with thymoglobulin and basiliximab ( > .05), respectively]. Older recipients treated with thymoglobulin showed the poorest survival in the Cox regression model adjusted for comorbidities. Thus thymoglobulin should be used with caution in older recipients during the present pandemic era.
PubMed: 36320365
DOI: 10.1093/ckj/sfac112 -
Surgical Case Reports Sep 2022Thrombotic microangiopathy is a syndrome characterized by microangiopathic hemolytic anemia and platelet aggregation, which is caused by endothelial injury,...
BACKGROUND
Thrombotic microangiopathy is a syndrome characterized by microangiopathic hemolytic anemia and platelet aggregation, which is caused by endothelial injury, microcirculation thrombosis, and fibrin deposition. Transplant-associated thrombotic microangiopathy rarely occurs after lung transplantation and the onset is generally later than that after bone marrow or other solid organ transplantation. The treatment is to stop administration of the causal agent, which is often a calcineurin inhibitor, such as tacrolimus and cyclosporine. We herein report the case of a patient with early post-transplant thrombotic microangiopathy after lung transplantation treated by introducing basiliximab and temporarily stopping any calcineurin inhibitors until resuming treatment with an alternative calcineurin inhibitor.
CASE PRESENTATION
A 58-year-old Asian woman underwent bilateral lung transplantation for hypersensitivity pneumonitis caused by an avian antigen, or bird fancier's lung disease. Postoperatively, she was started on triple immunosuppressive therapy, which included tacrolimus, mycophenolate mofetil, and steroids. On postoperative day 6, she developed thrombocytopenia followed by fever, hemolytic anemia, renal dysfunction, and purpura on her limbs and abdomen. She was diagnosed with transplant-associated thrombotic microangiopathy, and tacrolimus was thought to be the causal agent. We stopped tacrolimus and administered basiliximab. Then, she developed oliguria and needed continuous hemodiafiltration. On postoperative day 14, the platelet count recovered and she was switched from basiliximab to cyclosporine. Using this protocol, worsening thrombotic microangiopathy and acute rejection were avoided.
CONCLUSIONS
We report the case of a patient with early post-transplant thrombotic microangiopathy after lung transplantation that was treated with basiliximab. Switching from calcineurin inhibitors using basiliximab may be an option for treating thrombotic microangiopathy without increasing the risk of acute rejection.
PubMed: 36173476
DOI: 10.1186/s40792-022-01539-x -
Annals of Hepatology 2022
Topics: Basiliximab; Graft Rejection; Humans; Immunosuppressive Agents
PubMed: 35101617
DOI: 10.1016/j.aohep.2022.100679 -
Frontiers in Immunology 2021Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). Corticosteroid is the first-line... (Meta-Analysis)
Meta-Analysis
Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). Corticosteroid is the first-line treatment for aGVHD, but its response rate is only approximately 50%. At present, no uniformly accepted treatment for steroid-refractory aGVHD (SR-aGVHD) is available. Blocking interleukin-2 receptors (IL-2Rs) on donor T cells using pharmaceutical antagonists alleviates SR-aGVHD. This meta-analysis aimed to compare the efficacy and safety of four commercially available IL-2R antagonists (IL-2RAs) in SR-aGVHD treatment. A total of 31 studies met the following inclusion criteria (1): patients of any race, any sex, and all ages (2); those diagnosed with SR-aGVHD after HSCT; and (3) those using IL-2RA-based therapy as the treatment for SR-aGVHD. The overall response rate (ORR) at any time after treatment with basiliximab and daclizumab was 0.81 [95% confidence interval (CI): 0.74-0.87)] and 0.71 (95% CI: 0.56-0.82), respectively, which was better than that of inolimomab 0.54 (95% CI: 0.39-0.68) and denileukin diftitox 0.56 (95% CI: 0.35-0.76). The complete response rate (CRR) at any time after treatment with basiliximab and daclizumab was 0.55 (95% CI: 0.42-0.68) and 0.42 (95%CI: 0.29-0.56), respectively, which was better than that of inolimomab 0.30 (95% CI: 0.16-0.51) and denileukin diftitox 0.37 (95% CI: 0.24-0.52). The ORR and CRR were better after 1-month treatment with basiliximab and daclizumab than after treatment with inolimomab and denileukin diftitox. The incidence of the infection was higher after inolimomab treatment than after treatment with the other IL-2RAs. In conclusion, the efficacy and safety of different IL-2RAs varied. The response rate of basiliximab was the highest, followed by that of daclizumab. Prospective, randomized controlled trials are needed to compare the efficacy and safety of different IL-2RAs.
Topics: Antibodies, Monoclonal; Basiliximab; Daclizumab; Diphtheria Toxin; Drug Resistance; Graft vs Host Disease; Humans; Immunosuppressive Agents; Interleukin-2; Receptors, Interleukin-2; Recombinant Fusion Proteins; Steroids
PubMed: 34621279
DOI: 10.3389/fimmu.2021.749266 -
Translational Andrology and Urology Apr 2019ABO-incompatible living kidney transplantation (ABO-ILKT) is an effective option for increasing living kidney transplant opportunities. ABO-ILKT has been conducted in... (Review)
Review
ABO-incompatible living kidney transplantation (ABO-ILKT) is an effective option for increasing living kidney transplant opportunities. ABO-ILKT has been conducted in our institution since 1989 to widen the indication for living kidney transplantation. ABO-ILKT is considered to require extra treatment, and it has increased risks compared with ABO-compatible living kidney transplantation (ABO-CLKT). In the past two decades, some protocols have removed anti-blood-type antibodies to prevent the production of antibodies. Additionally, we have made considerable changes to our ABO-ILKT protocol as new immunosuppressive agents have been developed. Consequently, increased immunosuppression and immunological understanding have helped shape recent desensitization protocols. Herein, we review the history, therapeutic strategy, pathology, and future directions of ABO-ILKT. Our standard immunosuppressive regimen and desensitization protocol for ABO-ILKT recipients consist of low doses of tacrolimus (TAC), mycophenolate mofetil (MMF), and rituximab; several sessions of double filtration plasmapheresis; and basiliximab induction. We do not use thymoglobulin induction, intravenous immunoglobulin, or prophylactic post-transplant plasmapheresis. Recently, ABO-ILKT has been recognized as a useful alternative therapy for end-stage kidney disease with ABO-incompatibility, and its outcome is comparable to that of ABO-CLKT.
PubMed: 31080772
DOI: 10.21037/tau.2019.03.05