Acute Rejection In Transplant Patients Research Articles

Paxlovid with Caution: Novel Case of Paxlovid-Induced Tacrolimus Toxicity in a Cardiac Transplant Patient.

Tacrolimus is commonly used as a prophylactic against acute rejection in transplant patients. Tacrolimus toxicity has numerous presentations that have been well documented in the literature and can be induced by a wide variety of agents. We present a novel case of tacrolimus toxicity in a cardiac transplant patient induced by outpatient treatment for COVID-19 pneumonia with ritonavir-nirmatrelvir, which was successfully treated with phenytoin therapy.LEARNING POINTSRitonavir-nirmatrelvir is a newly approved antiviral therapy for COVID-19 to prevent hospitalization and is increasingly prescribed in the outpatient setting.Thorough assessment of drug interactions prior to starting ritonavir-nirmatrelvir can prevent tacrolimus toxicity in patients with solid organ transplants.Phenytoin increases the metabolism of tacrolimus and can be safely utilized to treat tacrolimus toxicity.

HLA-G 14bp Ins/Del Polymorphism in the 3'UTR Region and Acute Rejection in Kidney Transplant Recipients: An Updated Meta-Analysis.

Background and Objectives: Acute kidney injury (AKI) affects the survival rate of kidney transplant organs and patients. Acute rejection (AR) due to AKI may lead to kidney transplantation failure. It is known that there is a relationship between human leukocyte antigen-G (HLA-G), which is involved in immune regulation, and AR in transplant patients. Moreover, 14-bp insertion/deletion polymorphism in the 3′ untranslated region (UTR) region of the HLA-G gene is known to affect HLA-G expression. However, its relationship to AR is still controversial. The aim of this study was to investigate whether HLA-G 14-bp insertion/deletion polymorphism contributed to the development of AR in kidney transplant patients using a meta-analysis. Materials and Methods: To perform our meta-analysis, eligible studies about HLA-G 14-bp insertion/deletion polymorphism and AR were searched in electronic databases until 1 June 2021. Finally, a total of 336 patients with AR and 952 patients without AR in relation to kidney transplantation were analyzed from a total of nine studies. Results: In our results, the Del allele and Ins/Del+Del/Del and Del/Del genotypes significantly increased susceptibility of AR in Asian populations [odds ratio (OR) = 2.359, 95% confidence interval (CI) = 1.568–3.550, p = 3.8 × 10−5; OR = 3.357, 95% CI = 1.769–6.370, p = 0.002; OR = 2.750, 95% CI = 1.354–5.587, p = 0.0052 in each model, respectively]. Conclusions: Evidence of the present results indicate that HLA-G 14-bp insertion/deletion polymorphism is associated with susceptibility to AR in the Asian population.

Efficacy and Safety of Echocardiographic Guidance for Post-Transplant Endomyocardial Biopsy Sampling

Background: Endomyocardial biopsy is a very useful procedure to assess acute rejection in transplant patients, but it can causeseveral complications.Objective: The purpose of this study is to demonstrate the efficacy and safety of echocardiography as a guide for endomyocardialbiopsy sampling.Methods: A retrospective analysis of transplant patients undergoing endomyocardial biopsies was carried out between November2004 and November 2016. Demographic data and complications were analyzed with descriptive statistics.Results: A total of 200 patients underwent 2,665 endomyocardial biopsies, with an average of 13 procedures per patient. Complicationsoccurred in 5 patients: 2 pneumothorax (0.1%) and 3 transient alterations in the electrocardiogram (0.1%), and vascular accesscould not be achieved in 25 patients (0.9%). No patient died during the procedure or required emergency surgery to treat thecomplications.Conclusion: Endomyocardial biopsy guided by echocardiography is a safe procedure with a low rate of complications.

Induction therapy with two doses of daclizumab in heart transplantation: a prospective, multi centric clinical study. interim analysis

Immunoprophylaxis with daclizumab, a humanized anti-IL-2R alpha monoclonal antibody, has been shown to be effective in the prevention of acute rejection in transplant patients. These results encouraged us to initiate a pilot study in 40 heart transplant patients utilizing two dose of daclizumab, to determine the safety and efficacy of this regimen.

Lamivudine therapy for hepatitis B in renal transplantation

Antiviral therapies are associated with an increased risk of acute rejection in transplant patients. The aim of the present study was to evaluate the efficacy and safety of lamivudine therapy for hepatitis B virus (HBV) infection in renal transplant patients. Six patients were included in this study. They received 150 mg/day of lamivudine during a follow-up period of 24 months. The laboratory tests monitored were HBV DNA, HBsAg, HBeAg, ALT, gamma-GT, serum creatinine and blood cyclosporine levels. The HBV DNA became undetectable in four patients as early as in the third month of treatment. After six months, the viral load was also negative in the other two patients, and remained so until 18 months of follow-up. The medication was well tolerated with no major side effects. Lamivudine was safe and effective in blocking HBV replication in renal transplant patients without any apparent increase in the risk of graft failure for the 24-month period of study.

Pentoxifylline Promotes Replication of Human Cytomegalovirus In Vivo and In Vitro

OKT3 monoclonal antibody (MoAb) therapy is well established in the prevention and therapy of acute rejection in transplant patients. Unfortunately, this therapy is associated with several short-term (cytokine release syndrome) and long-term (infections, EBV-related lymphoma) side effects. Recently, we were able to demonstrate an association between the TNF alpha release following the first OKT3 MoAb infusions and the appearance of human cytomegalovirus (HCMV) reactivation several days later. In order to prevent this TNF alpha associated HCMV reactivation patients were additionally treated with pentoxifylline (PTX), a methylxanthine derivative that has been shown to suppress TNF alpha induction. Although the TNF alpha peak plasma level following OKT3 MoAb treatment was markedly reduced, the incidence of HCMV reactivation and HCMV disease was not influenced. In transient transfection experiments using HCMV immediate early enhancer/promoter CAT reporter gene constructs PTX enhanced the promoter activity independently from TNF alpha in premonocytic cells. Furthermore, PTX acted synergistically with TNF alpha. In virus-infected human embryonal lung fibroblasts HCMV replication was triggered in the presence of both PTX and TNF alpha, while either substance alone had only marginal effects. The stimulatory effect of PTX on the immediate early (IE) enhancer/promoter was mediated via CREB/ ATF, a eukaryotic transcription factor that binds to the 19 bp sequence motif in the enhancer region, while TNF alpha stimulation was mediated by activation of the transcription factor NF-kappaB and its binding to the 18 bp sequence motif in the enhancer. These data suggest a potential side effect of cAMP-elevating drugs such as PTX.

Pentoxifylline Promotes Replication of Human Cytomegalovirus In Vivo and In Vitro

AbstractOKT3 monoclonal antibody (MoAb) therapy is well established in the prevention and therapy of acute rejection in transplant patients. Unfortunately, this therapy is associated with several short-term (cytokine release syndrome) and long-term (infections, EBV-related lymphoma) side effects. Recently, we were able to demonstrate an association between the TNFα release following the first OKT3 MoAb infusions and the appearance of human cytomegalovirus (HCMV) reactivation several days later. In order to prevent this TNFα associated HCMV reactivation patients were additionally treated with pentoxifylline (PTX), a methylxanthine derivative that has been shown to suppress TNFα induction. Although the TNFα peak plasma level following OKT3 MoAb treatment was markedly reduced, the incidence of HCMV reactivation and HCMV disease was not influenced. In transient transfection experiments using HCMV immediate early enhancer/promoter CAT reporter gene constructs PTX enhanced the promoter activity independently from TNFα in premonocytic cells. Furthermore, PTX acted synergistically with TNFα. In virus-infected human embryonal lung fibroblasts HCMV replication was triggered in the presence of both PTX and TNFα, while either substance alone had only marginal effects. The stimulatory effect of PTX on the immediate early (IE) enhancer/promoter was mediated via CREB/ATF, a eukaryotic transcription factor that binds to the 19 bp sequence motif in the enhancer region, while TNFα stimulation was mediated by activation of the transcription factor NF-kB and its binding to the 18 bp sequence motif in the enhancer. These data suggest a potential side effect of cAMP-elevating drugs such as PTX.