Calcineurin inhibitors constitute a cornerstone of immunosuppressive therapy in kidney transplant recipients. There are two main formulations of tacrolimus (Tac) which exhibit a prolonged-release ...mode of action: Advagraf® (MR-4) and Envarsus® (LCPT). However, they are not bioequivalent. Data comparing both once-daily prolonged-release formulations of Tac are insufficient.
The aim of the study was to compare safety and efficacy profiles of once-daily LCPT and MR-4 formulations of tacrolimus in adult kidney transplant recipients.
An observational, cohort single-center study was performed. One hundred fifteen kidney transplant recipients transplanted between 2016 and 2019 were enrolled to the study (59 vs 56, Envarsus® vs Advagraf®, respectively). Safety and efficacy profiles were assessed.
Patient and graft survival at 12 and 24 months did not differ between the groups. There were no significant differences in serum creatinine at any timepoint. C/D ratio in the LCPT group was significantly higher at 12 and 24 months. Sepsis occurrence was more frequent in MR-4 group at 12 months.
Both prolonged-release formulations of tacrolimus are safe and effective in immunosuppressive therapy in kidney transplant recipients.
Kidney transplantation is the treatment of choice in end-stage renal disease. The main issue which does not allow to utilize it fully is the number of organs available for transplant. Introduction of ...highly effective oral direct-acting antivirals (DAAs) to the treatment of chronic hepatitis C virus infection (HCV) enabled transplantation of HCV viremic organs to naive recipients. Despite an increasing number of reports on the satisfying effects of using HCV viremic organs, including kidneys, they are more often rejected than those from HCV negative donors. The main reason is the presence of HCV viremia and not the quality of the organ. The current state of knowledge points to the fact that a kidney transplant from an HCV nucleic acid testing positive (NAT+) donor to naive recipients is an effective and safe solution to the problem of the insufficient number of organs available for transplantation. It does not, however, allow to draw conclusions as to the long-term consequence of such an approach. This review analyzes the possibilities and limitations of the usage of HCV NAT + donor organs. Abbreviations: DAA: direct-acting antivirals; HCV: hepatitis C virus; NAT: nucleic acid testing; OPTN: Organ Procurement and Transplantation Network; KDIGO: Kidney Disease: Improving Global Outcomes; Ab: antigen; eGFR: estimated glomerular filtration rate; D: donor; R: recipient; CMV: cytomegalovirus; HBV: hepatitis B virus; UNOS: United Network for Organ Sharing; PHS: Public Health Service; EBR/GZR: elbasvir/grazoprevir; SVR: sustained virologic response; RAS: resistance-associated substitutions; SOF: soforbuvir; GLE/PIB: glecaprevir/pibrentasvir; ACR: acute cellular rejection; AR: acute rejection; DSA: donor-specific antibodies; KTR: kidney transplant recipients; AASLD: American Association for the Study of Liver Disease; IDSA: Infectious Diseases Society of America; PPI: proton pump inhibitors; CKD: chronic kidney disease; GN: glomerulonephritis; KAS: The Kidney Allocation system
Background: Molnupiravir is approved for the treatment of adult patients with mild to moderate COVID-19. The main goal of the treatment is to reduce hospitalization and mortality rate. This study ...aimed at the all-cause hospitalization and all-cause death assessment in patients at high risk of severe COVID-19 treated with molnupiravir. Methods: This was a prospective, observational single center study. Non-hospitalized patients with SARS-CoV-2 infection, COVID-19 symptoms with the onset of up to 5 days, and at high risk of severe COVID-19 illness received molnupiravir based on attending physician decisions. Results: In total, 107 patients were enrolled. Adverse events were reported in 28.0% of patients, with nausea and abdominal pain being the most commonly observed. No treatment-emergent AEs resulted in therapy discontinuation. Overall, 15 patients required hospitalization. During the observation, 2.8% (n = 3) of patients subsequently died. All deaths were considered to be related to COVID-19 complications. Age over 65 years, heart failure, and ischemic heart disease showed a significant correlation with the severe course of COVID-19. Conclusion: Molnupiravir may be perceived as an alternative treatment for patients with immunosuppression and advanced chronic kidney disease. Nevertheless, further studies are required to conclusively establish a role for molnupiravir in future COVID-19 treatment recommendations.
Post-transplant antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) monitoring in kidney transplant recipients remains unclear and is currently under investigation. The ...pathogenicity of anti-HLA DSAs is determined by antibody classes, specificity, mean fluorescent intensity (MFI), C1q-binding capacity, and IgG subclasses. The aim of this study was to investigate the association of circulating DSAs and their characteristics with renal allograft long-term outcomes. The study included 108 consecutive patients from our transplant center who underwent kidney allograft biopsy between November 2018 and November 2020, 3 to 24 months after kidney transplantation. At the time of biopsy, patients' sera were collected for analysis of anti-HLA DSAs. Patients were followed for a median time of 39.0 months (Q1-Q3, 29.8-45.0). Detection of anti-HLA DSAs at the time of biopsy (HR = 5.133, 95% CI 2.150-12.253,
= 0.0002) and their C1q-binding capacity (HR = 14.639, 95% CI 5.320-40.283,
≤ 0.0001) were independent predictors of the composite of sustained 30% reduction from estimated glomerular filtration rate or death-censored graft failure. Identification of anti-HLA DSAs and their C1q-binding capacity could be useful in identifying kidney transplant recipients at risk for inferior renal allograft function and graft failure. Analysis of C1q is noninvasive, accessible, and should be considered in clinical practice in post-transplant monitoring.
The post-transplant evolution of antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) includes three clinical patterns: resolved preformed DSAs, persistent preformed DSAs, and de ...novo DSAs. The aim of this retrospective study was to analyze the impact of resolved preformed, persistent preformed, and de novo anti-HLA-A, -B, and -DR DSAs in kidney transplant recipients on long-term renal allograft outcomes. This is a post hoc analysis of the study conducted in our transplant center. One hundred eight kidney transplant recipients were included in the study. Patients were followed for a minimum of 24 months after allograft biopsy, which was performed 3 to 24 months after kidney transplantation. The identification of persistent preformed DSAs at the time of biopsy was the most significant predictor of the combined endpoint of the study (>30% decline in estimated glomerular filtration rate or death-censored graft loss; HR = 5.96, 95% CI 2.041-17.431,
= 0.0011), followed by the occurrence of de novo DSAs (HR = 4.48, 95% CI 1.483-13.520,
= 0.0079). No increased risk was observed in patients with resolved preformed DSAs (HR = 1.10, 95% CI 0.139-8.676,
= 0.9305). Patients with resolved preformed DSAs have similar graft prognoses as patients without DSAs, therefore, the persistence of preformed DSAs and development of de novo DSAs are associated with inferior long-term allograft outcomes.
Liver transplantation is a life-saving and successful therapeutic procedure which is more and more frequent worldwide, also among women of reproductive age. Consequently, there is an increasing ...number of reports of pregnancy following liver transplantation, but doubts still exist regarding preconception counseling and the optimal method of managing pregnancy. The aim of this study was to report and evaluate pregnancy outcomes in women who had undergone liver transplantation.
We retrospectively analyzed female patients after orthotopic liver transplantation who reported pregnancy and were under medical care of a single transplant center.
We identified 14 pregnancies in 10 women who had undergone liver transplantation (12 childbirths, one induced abortion due to fetal death in the first trimester, one pregnancy is still ongoing). Causes of transplantation include congenital or acquired disorders and the most common indication was autoimmune hepatitis (50%). The mean age at the point of transplantation was 28.5 (range 21-36), mean maternal age at pregnancy was 32 (range 26-43), and transplant-to-pregnancy interval was 4.07 years (range 1.5-7). The mean gestational week was 36.67 (range 31-40). Immunosuppression was maintained with combinations of prednisone (n = 11), tacrolimus (n = 13), and azathioprine (n = 8) prior to and during pregnancy. Two pregnancies were unintended, so women took mycophenolate mofetil in the first weeks of gestation. Another two women stopped taking azathioprine due to increasing anemia. Maternal complications included increase of aspartate transaminase and alanine transaminase (n = 2), anemia (n = 4) and hyperthyroidism (n = 2). Among the 12 childbirths, five (41.67%) were preterm. Only five women entered labor spontaneously, while seven (58,33%) had cesarean delivery.
Pregnancy after liver transplantation can achieve relatively favorable outcomes. Liver transplantation does not influence women's fertility and, during pregnancy, we report low rates of minor graft complications. A multidisciplinary team should be involved in contraceptive, fertility and consequently pregnancy counseling of female transplant recipients.
Metabolic syndrome (MS) constitutes an important source of cardiovascular- and cancer-related morbidity and mortality in the general population. Limited information is available on whether these ...findings can be directly extrapolated to liver recipients. This study aimed to investigate the impact of post-transplant MS present 1 year after liver transplantation on survival rates, risk of major cardiovascular events (CVEs), and de novo malignancies.
Adult deceased-liver-donor recipients who underwent transplantation in our centre between 2010 and 2019 and reached at least 1 year of post-transplantation follow-up were eligible.
Of 259 enrolled patients, 20% developed post-transplant MS 1 year after the procedure. The presence of post-transplant MS at 1 year did not affect all-cause mortality (
= 0.144) and risk of de novo malignancies (
= 0.198) in liver recipients. However, it was associated with an overall and time-dependent increase in the risk of major CVEs (
< 0.001). MASH aetiology of liver disease, pre-existing major CVEs, and development of de novo malignancy were independent predictors of all-cause mortality in liver recipients.
New onset MS exerts a wide-ranging effect on the post-transplant prognosis of liver recipients. Obtaining optimal control over all modifiable metabolic risk factors is central to improving long-term outcomes in this population.
Abstract
Background
Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in ...Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation.
Methods
All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks.
Results
The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes.
Conclusions
The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.
Infection with cytomegalovirus (CMV) remains a major problem in kidney transplant recipients, resulting in serious infectious complications and occasionally mortality. Accumulating evidence indicates ...that natural killer cell immunoglobulin-like receptors (KIRs) and their ligands affect the susceptibility to various diseases, including viral infections (e.g., CMV infection). We investigated whether KIR genes and their ligands affect the occurrence of CMV infection in a group of 138 kidney transplant recipients who were observed for 720 days posttransplantation. We typed the recipients for the presence of KIR genes (human leukocyte antigen C1 HLA-C1, HLA-C2, HLA-A, HLA-B, and HLA-DR1) by polymerase chain reaction with sequence-specific primers. The multivariate analysis revealed that the lack of
(
= 0.035), the presence of
(
= 0.075), and the presence of
⁻HLA-C1 (
= 0.044) were risk factors for posttransplant CMV infection. We also found that a lower estimated glomerular filtration rate (
= 0.036), an earlier time of antiviral prophylaxis initiation (
= 0.025), lymphocytopenia (
= 0.012), and pretransplant serostatus (donor-positive/recipient-negative;
= 0.042) were independent risk factors for posttransplant CMV infection. In conclusion, our findings confirm that the KIR/HLA genotype plays a significant role in anti-CMV immunity and suggest the contribution of both environmental and genetic factors to the incidence of CMV infection after kidney transplantation.
Obesity and diabetes mellitus epidemics exert a measurable impact on the liver transplant (Ltx) population. This study aimed to investigate the metabolic profile of Ltx recipients and its association ...with body fat distribution. Adults who underwent de novo elective cadaveric-donor Ltx were eligible. Metabolic syndrome (MS) was diagnosed based on the adapted International Diabetes Federation, the American Heart Association, and the National Heart, Lung, and Blood Institute guidelines. We recruited 100 patients with a mean age of 54 years, of whom 70% were men. Overall, 54% met the criteria for MS, most of which comprised new-onset cases. Excessive fat accumulation in liver donors was found to be associated with an increased metabolic risk in liver recipients. Haemoglobin A1C (OR: 8.962, 95% CI: 2.188–84.545, p = 0.013), ferritin (OR: 1.024, 95% CI: 1.005–1.054, p = 0.038), and de novo hypertriglycaeridemia (OR 27.957, 95% CI: 2.626–752.121, p = 0.014) were found to be independently associated with de novo MS. After a step-wise multivariate analysis, only the anthropometric obesity indices were significantly associated with abdominal fat distribution in Ltx recipients. Metabolic complications were common in liver recipients. Both pre- and post-Ltx factors impacted MS development in liver recipients and determined abdominal fat distribution.
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