Kidney Transplant Recipients Research Articles

Corrigendum: Glycolysis Changes in Alloreactive Memory B Cells in Highly Sensitized Kidney Transplant Recipients Undergoing Desensitization Therapy

Corrigendum: Glycolysis Changes in Alloreactive Memory B Cells in Highly Sensitized Kidney Transplant Recipients Undergoing Desensitization Therapy

Predicting the risk of pulmonary infection after kidney transplantation using machine learning methods: a retrospective cohort study.

Pulmonary infection is the most common and serious complication after kidney transplantation that affects the survival of the transplanted kidney and the quality of life of patients. This study aims to construct a machine learning model for predicting the risk of pulmonary infection after kidney transplantation. We recruited 857 kidney transplant recipients from January 1, 2016, to December 31, 2021, in the Department of Nephrology, the First Affiliated Hospital of the University of Science and Technology of China. First, the distribution of baseline characteristics between patients with and without postoperative pulmonary infections was analyzed. Subsequently, six machine learning models were constructed to predict the risk of postoperative pulmonary infections. Finally, these models were subjected to external validation using an independent cohort. The performance of themodels was evaluated by area under the receiver operating characteristic curve (AUC). Among kidney transplant recipients, a total of 186 individuals developed pneumonia, with 144 cases in the training cohort and 42 cases in the external validation cohort. The AUC range of the six machine learning models for predicting the risk of postoperative pulmonary infection was 0.758-0.822 for the training cohort and 0.642-0.795 for the testing cohort. Among the models assessed, the gradient boosting machine demonstrated the most favorable predictive accuracy. Our study has developed a predictive model for assessing the risk of pulmonary infection after kidney transplantation, thereby providing a valuable foundation for the effective management of kidney transplant recipients.

Prediction of Allograft Failure in Pediatric Kidney Transplant Recipients: A Validation Study of the Four-Variable Kidney Failure Risk Equation

Prediction of Allograft Failure in Pediatric Kidney Transplant Recipients: A Validation Study of the Four-Variable Kidney Failure Risk Equation

Changes in Donor-Derived Cell-Free DNA Before and After Rejection and De Novo DSA Detection in Primary and Repeat Kidney Transplant Recipients.

Serial monitoring of dd-cfDNA and change from baseline can provide meaningful information beyond absolute thresholds. We describe dd-cfDNA trajectories from the baseline before and after acute rejection (AR) and de novo donor-specific antibodies (dnDSA) detection in kidney transplant recipients (KTRs). We included KTR from 02/2019 to 03/2022 with serial dd-cfDNA. The primary analysis compared the time-varying change in dd-cfDNA from baseline in KTR first AR on biopsy [AR] to patients with no-AR on biopsy [no-AR]. 151 KTR were analyzed (AR=56 KTR, no-AR=95 KTRs). In the AR group, dd-cfDNA rose ahead of diagnosis: median rise from baseline was 75% at -3 months, 32% at -2 months, and 325% at -1 month before biopsy. At the time of biopsy, the median rise in dd-cfDNA from baseline was 291% (IQR [interquartile range] 88%-1081%) in AR and 17% (IQR 0%- 194%) in no-AR (p<0.0001). Following treatment, dd-cfDNA values fell in the AR group with a median change from baseline of 94.7% at +1 month, 10.5% at +2 months, and 0% at +3 months. These trajectories were not observed in the no-AR group. Similarly, there were no significant differences in eGFR (estimated glomerular filtration rate) trajectories between the two groups. The median change from baseline to dnDSA detection was 141% (IQR 112%-574%). In KTRs with persistent rejection, median dd-cfDNA was 0.95% (IQR 0.44-1.8) compared to 0.19% (IQR 0.12-0.31) in subjects with no rejection on follow-up (p<0.001). The significant changes from baseline observed before and after AR show how serial monitoring enhances dd-cfDNA utility and allows for earlier identification of evolving injury and monitoring treatment response.

Association between salivary microbiota and tacrolimus pharmacokinetic variability in kidney transplant

Kidney transplantation (KT) serves as a highly effective treatment for end-stage renal disease (ESRD). Nonetheless, the administration of tacrolimus, a commonly used immunosuppressant in KT, faces challenges due to the lack of dependable biomarkers for its efficacy and the considerable variability in tacrolimus pharmacokinetics (TacIPV). In this study, 183 saliva samples from 48 KT recipients under tacrolimus therapy, alongside 9 healthy control samples, were subjected to 16S rRNA sequencing. The analysis revealed significant differences in the composition of salivary microbiota among KT recipients, patients with ESRD, and healthy controls. Moreover, trough blood concentrations (C0) of tacrolimus were associated with alterations in microbiota composition. Notably, Capnocytophage consistently exhibited a negative correlation in both group-level and individual trends. Furthermore, distinct taxa were identified that effectively distinguished recipients with varying TacIPV, as demonstrated by a cross-validation random forest model (mean AUC = 0.7560), with Anaerolinea emerging as a prominent contributor to the classifier. These findings suggest that salivary microbiota is closely linked to tacrolimus C0 levels and could aid clinicians in differentiating KT recipients based on TacIPV.

Cilgavimab and tixagevimab as pre-exposure prophylaxis in vaccine non-responder kidney transplant recipients during a period of prevalent SARS-CoV-2 BA.2 and BA.4/5 variants—a prospective cohort study (RESCUE-TX)

The response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination is severely impaired in patients on maintenance immunosuppression after kidney transplantation. We conducted a prospective cohort study of 194 kidney transplant recipients (KTR) who exhibited no response to SARS-CoV-2 vaccinations (i.e., SARS-CoV-2 spike protein antibodies ≤264 U/mL) and had no prior documented infection. Patients received 300mg of cilgavimab/tixagevimab as SARS-CoV-2 pre-exposure prophylaxis (PrEP) between March 4, 2022, and May 3, 2022 and were contrasted to a matched cohort of 186 KTRs also without immunization again defined as SARS-CoV-2 spike protein antibodies ≤264 U/mL and no documented prior infection. The primary outcome was the serum kinetics of cilgavimab/tixagevimab, the secondary endpoints were time to SARS-CoV-2 breakthrough infection, severity of disease and variant specific live viral invitro neutralization tests of patient sera. Longitudinal serum level monitoring showed a half-life of 91 days for both antibodies (95% CI 86-95 days for cilgavimab and 85-96 days for tixagevimab) in KTRs. Invitro neutralization tests showed effectiveness against the BA.2 omicron subvariant but not BA.5. The cumulative incidence of SARS-CoV-2 infections until May 15, 2022, (BA.2 dominance) was 15/194 vs 36/186 in the PrEP and control group respectively (OR=0.35, 95% CI 0.18-0.66) but was not different thereafter (BA.4/5 dominance). The number of severe infections during the BA.2 period was lower in the prophylaxis than in the control group (OR=0.37, 95% CI 0.17-0.79). This study showed that SARS-CoV-2 PrEP with cilgavimab/tixagevimab demonstrated clinical effectiveness against variants that are neutralised (BA.2) but not against BA.4/5. This study was funded by the Medical University of Vienna and an unrestricted grant from AstraZeneca (ESR-21-21585).

Association of PIRCHE-II score with anti-donor T-cell response and risk of de novo donor-specific antibody production in kidney transplant recipients

BackgroundDe novo donor-specific antibodies (dnDSAs) affect long-term outcomes of kidney transplantation (KT). A higher Predicted Indirectly ReCognizable Human Leukocyte Antigen (HLA) Epitopes (PIRCHE-II) score correlates with various clinical outcomes, including dnDSA formation. However, a detailed analysis of the relationship between the PIRCHE-II score and anti-donor T-cell response is lacking. Therefore, this study investigated the relationship between PIRCHE-II scores associated with dnDSA formation and mixed lymphocyte reaction results of anti-donor T-cell response. MethodsData of 105 adult living-donor KT recipients were retrospectively assessed. ResultsOf the 105 patients, 13.3 % developed dnDSAs during the observation period. The PIRCHE-II score at the HLA-DQ locus (PIRCHE-DQ) was significantly higher in patients with dnDSA formation than in those without. The incidence of dnDSA formation was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group. The proportion of patients with increased anti-donor T-cell response was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group before KT and at 4 and 5 years after KT. ConclusionsPIRCHE-DQ may predict dnDSA formation and anti-donor T-cell response. Reducing the immunosuppressive drug dose in cases of high PIRCHE-DQ might not be prudent.

Effect of mitochondrial oxidative stress on Regulatory T Cell manufacturing for clinical application in transplantation: results from a pilot study

The manufacturing process of Regulatory T (Treg) cells for clinical application begins with the positive selection of CD25+ cells using superparamagnetic iron-oxide nanoparticle (SPION)-conjugated anti-CD25 antibodies (spCD25) and immunomagnetic cell separation technology. Our findings revealed that the interaction of spCD25 with its cell target induced the internalization of the complex spCD25-Interleukin-2 Receptor. Accumulation of intracellular spCD25 triggered oxidative stress, causing delayed Treg expansion and temporary reduction in suppressor activity. This activation delay hindered the efficient generation of clinically competent cells. During this early phase, Treg cells exhibited elevated mitochondrial superoxide and lipid peroxidation levels, with concomitant decrease on mitochondrial respiration rates. The results uncovered the increased mitochondrial unfolded protein response (mitoUPR). This protective, redox-sensitive activity is inherent of Tregs when contrasted with homologous, spCD25-treated, conventional T cells. While the temporary effects of spCD25 on clinically competent cells did not impede their use in a safety/feasibility pilot study with kidney transplant recipients*, it is reasonable to anticipate a potential reduction in their therapeutic efficacy. The mechanistic understanding of the adverse effects triggered by spCD25 is crucial for improving the manufacturing process of clinically competent Treg cells, a pivotal step in the successful implementation of immune cell therapy in transplantation.*Clinical trial registration number NCT03284242 at ClinicalTrials.gov.

Investigation of Nosocomial Urinary Tract Infections Post Transplantation, Main Pathogens, and Sensitivity Tests

Background: Regarding end-stage organ disease, transplantation is recommended as the best therapeutic management. After organ transplantation, the incidence of nosocomial urinary tract infections (NUTIs) due to multidrug-resistant Gram-negative bacilli increases. Aim: The study aimed to investigate NUTIs post-transplantation, the main pathogens involved, and sensitivity tests conducted in a tertiary hospital in Isfahan, Iran. Methods: A retrospective survey on patients admitted to a tertiary hospital in Isfahan (Alzahra), Iran, was performed between 27 March, 2017, and 9 February, 2022. The information recorded included the date of infection, date of hospitalization, gender, age, type of pathogens, and resistance or sensitivity to antibiotics. Results: 73 kidney transplant recipients (61% females) with a mean age of 43. 2 ± 15.1 years were included. Within this population involving both genders, the main pathogens involved in NUTIs were as follows: Escherichia coli (30%), Klebsiella pneumonia (19%), Candida albicans and non-albicans (14%), Enterococcus faecalis (12%), Enterobacteriaceae (8%), Pseudomonas aeruginosa (6%), Staphylococcus spp. (6%), Acinetobacter baumannii (4%), and Streptococcus spp. (4%). Antibiotic susceptibility testing showed the most sensitivity of isolates against amikacin (n=29; 66%), meropenem (n= 28; 64%), piperacillin/tazobactam (n=26; 54%), cefepime (n= 25; 40%), ceftazidime (n= 27; 30%), ciprofloxacin (n= 40; 18%), and co-trimoxazole (n= 29; 10%). Conclusion: Escherichia coli, Klebsiella pneumonia, and Candida spp. were the major causes of NUTIs within the studied organ-transplanted recipients. Amikacin, meropenem, and piperacillin/ tazobactam have shown more than 50% sensitivity against isolates. Further evidence-based pharmacotherapy investigations associated with the different spectrum antibiotics and overall antimicrobial success rate is recommended to be advantageous.

Clinical outcomes of pediatric kidney replacement therapy after childhood cancer – ESPN/ERA Registry study

Cancer and its treatment may lead to kidney injury and need for kidney replacement therapy (KRT). We identified 287 pediatric KRT patients with a malignancy history from the ESPN/ERA Registry. Of these, 197 had cancer as a primary cause of KRT (group 1) and 90 had a malignancy diagnosis before KRT (group 2). Two matched controls without malignancy were randomly selected for each patient. Data were complemented with a questionnaire. Median time to kidney transplantation (KT) from KRT initiation was 2.4 (IQR: 1.5–4.7), 1.5 (IQR: 0.4–3.3), 3.6 (IQR: 1.3–Q3 not reached), and 1.1 (IQR: 0.3–3.6) years for group 1, their controls, group 2 and their controls, respectively. Overall 10-year mortality on KRT was higher among cancer patients vs. controls in group 1: 16% vs. 9% (aHR 2.02, 95% CI: 1.21–3.37) and in group 2: 23% vs. 14% (aHR 2.32, 95% CI: 1.11–4.85). In contrast, 10-year patient survival after first KT was comparable to controls (93% vs. 96%; 100% vs. 94%, in groups 1 and 2, respectively). In summary, childhood cancer survivors’ KT was delayed, their overall mortality on KRT was increased, but once transplanted, their long-term outcome was similar to other KT recipients.

Predictors of self-care in kidney transplant patients according to preoperative dialysis: A comparative study

BackgroundPreemptive kidney transplantation (PKT) is associated with reduced dialysis-related morbidity and improved graft survival, which has led to an increase in the prevalence of PKT. The distinct clinical pathways of PKT and non-preemptive kidney transplantation (NPKT) patients may affect their ability to perform self-care, a key factor in post-transplant recovery. However, there is ongoing controversy regarding which group demonstrates better self-care abilities, highlighting the need to explore the factors influencing self-care in each group. ObjectivesThis study aims to identify and compare predictors of self-care in PKT and NPKT groups. MethodsWe collected data from 209 KT recipients, consisting of 101 PKT and 108 NPKT patients, using self-administered questionnaires. These questionnaires assessed general and disease-specific characteristics, stress, social support, and self-care behaviors. Data were analyzed using descriptive statistics, t-tests, ANOVA, and multiple regression analysis. ResultsThe study identified significant predictors of self-care among both PKT and NPKT patients. For PKT patients, marital status (β =.19, p=.033) and family support (β =.28, p=.006) are key predictors of self-care, with those having spousal support and strong family networks reporting better self-care levels. Conversely, in NPKT patients, significant predictors of self-care included marital status (β =.31, p=.001), employment status (β =.29, p=.007), post-transplantation duration (less than 36 month) (β =.-.22, p=.015), post-transplantation duration (36-72 month) (β =.-.33, p=.001), and stress levels (β =-.20, p=.028). ConclusionsThe study provides valuable insights into the predictors of self-care based on preoperative dialysis status, illustrating distinct predictors between the growing population of PKT and NPKT patients. These findings emphasize the need for personalized nursing strategies to enhance post-transplant self-care, tailored to individual patient characteristics.

Immunosuppressive Therapy, Puberty and Growth Outcomes in Pediatric Kidney Transplant Recipients: A Pragmatic Review.

Kidney transplantation in children with end-stage kidney disease significantly enhances survival and quality of life but poses unique challenges related to chronic immunosuppressive therapy. In fact, despite being essential for preventing organ rejection, immunosuppressive therapy can have significant side effects specific to pediatric patients, such as adverse impacts on physiological growth, puberty, and fertility. The resulting short stature and delayed or incomplete pubertal development can profoundly affect young patients' psychological and social well-being, impacting self-esteem and overall quality of life, and may significantly hamper compliance and therapeutic adherence. Most studies on immunosuppression in pediatric kidney transplant recipients focus on general side effects and outcomes like long-term graft survival or acute complications. On the other side, there is limited evidence in the current literature on the specific issues of growth, puberty, and fertility in this patient population. In this pragmatic review, we aimed to summarize the most relevant information available on these critical aspects of post-transplant management in pediatric patients, also providing some practical indications on management strategies for minimizing these often neglected but still important complications.

Torque Teno Virus Control by the Classical Pathway of Complement Activation-A Retrospective Analysis From a First-in-Human Trial Utilizing Sutimlimab.

Torque Teno virus (TTV) load is linked with the functionality of its host's immune system and has been proposed as a potential monitoring tool for immune-modulating therapy. However, the immunological mechanisms of TTV control are incompletely understood. To assess the effect of the classical complement pathway on TTV, 64 healthy volunteers and 10 kidney transplant recipients treated with the anti-C1s antibody sutimlimab were analyzed for serum TTV copy numbers (c/mL) by qPCR. Overall, a correlation was observed between the decrease in complement activity caused by sutimlimab and the TTV load increase (ρ = -0.367, p < 0.001). Subgroup analysis indicated a trend toward TTV load increase in healthy volunteers following the highest sutimlimab dose compared to baseline (100 mg/kg body weight; median 3.5 log10 c/mL, interquartile range [IQR] 2.8-4.4 vs. 2.9 log10 c/mL, 0.8-3.5; p = 0.063). Administering multiple lower doses (30 mg/kg) also showed a trend toward TTV load increase in healthy volunteers (1.8 log10 c/mL, 0-2.3 vs. 1.9, 1.3-2.8; p = 0.054) and a significant increase in transplant recipients (3.5 log10 c/mL, 3.0-6.1 vs. 4.1, 3.5-6.4; p = 0.004). This report suggests a role for the classical complement pathway in controlling TTV load.

Long-Term Outcomes of Induction Immunosuppression for Kidney Transplant Recipients With HIV Who Have Average Immunologic Risk: An Inverse Probability Treatment Weighting Analysis

We analyzed the Scientific Registry of Transplant Recipients (2004-2022) for primary kidney recipients with HIV who had average immunologic risk and were discharged on tacrolimus/mycophenolate mofetil (with or without corticosteroids). Recipients were grouped by induction type: rabbit antithymocyte globulin (r-ATG, n=688) and human interleukin-2 receptor antagonist (IL2Ra, n=467). Kaplan-Meier curves were generated to examine recipient and graft survival by induction type. We used mixed Cox proportional hazard models to determine associations between induction type and outcomes of interest, with adjustments for recipient and donor factors and transplant center as a random effect. Regression with propensity score weighting reduced selection bias from nonrandom induction allocation. The unadjusted 10-year survival rate was 57% for those receiving r-ATG and 64% for those receiving IL2Ra (P<.001). Adjusted risk of death was significantly lower for IL2Ra induction than r-ATG induction with Cox multivariable (hazard ratio, 0.65; 95% CI, 0.47-0.91; P=.01) and inverse probability treatment weighting (hazard ratio, 0.38; 95% CI, 0.29-0.50; P<.01) models. Death-censored kidney graft survival did not differ by induction type in either model. The 1-year rejection rate was 10.1% and 11.6% for r-ATG and IL2Ra recipients, respectively (P=.52). Overall, IL2Ra conferred better long-term survival than r-ATG without increased risk of graft loss.

Trends in Kidney Allograft Failure Among First-Time Transplant Recipients in the United States

Rationale & ObjectiveThe management and outcomes of kidney transplant recipients have evolved over the past three decades. This study of U.S patients whose first kidney allograft failed sought to understand long-term trends in subsequent waitlisting, re-transplantation, and all-cause mortality. Study DesignRetrospective cohort study. Setting & ParticipantsPatients recorded in the United States Renal Data System (USRDS) whose first kidney allograft failed between 1990 and 2019. ExposureThe 5-year period in which the allograft failure occurred: 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014, or 2015-2019. Outcomes1) Waitlisting for re-transplantation, 2) re-transplantation, and 3) all-cause mortality following first allograft failure. Analytical ApproachCompeting risk survival analyses using the approach described by Fine and Gray were used for the outcomes of waitlisting and re-transplantation. Cox proportional hazards models were used for the outcome of all-cause mortality. ResultsThe absolute number of patients whose allograft failed and started dialysis increased from 3,197 in 1990 to 5,821 in 2019. Compared to 1990-1994, the rate of waitlisting for a second transplant increased with each subsequent 5-year period, peaking between 2005-2009 before decreasing again subsequently. The rate of re-transplantation following allograft failure decreased by 9%, 14%, 18%, 7%, and 11% in the sequential 5-year eras; and the mortality rate was 25% lower in 2015-2019 (HR=0.75, 95% CI, 0.72-0.77) compared to 1990-1994. Women had a reduced rate of waitlisting (HR 0.93, 95% CI 0.91-0.95) and lower rate of re-transplantation (HR 0.93, 95% CI 0.91, 0.95) compared to men. Compared to White patients, African-American and Hispanic patients had significantly lower rates of waitlisting, re-transplantation, and mortality. LimitationsRetrospective data that lacks granular clinical information. ConclusionsDuring the past three decades, among patients whose first kidney allograft failed and subsequently initiated dialysis, the rates of waitlisting for re-transplantation increased while the rates of re-transplantation and mortality decreased. Race-, ethnicity-, and sex-based disparities in waitlisting and re-transplantation were observed and warrant further investigation.

Anti-PD-1 immunotherapy for the treatment of metastatic urothelial carcinoma in a kidney transplant recipient: a case report

BackgroundImmune checkpoint inhibitor (ICI) therapy has been widely investigated in urothelial carcinoma; however, the utility of ICI therapy in the treatment of organ transplant recipients with metastatic urothelial carcinoma (mUC) is unclear. We herein report the first case of a first-line anti-programmed cell death-1 (anti-PD-1) monotherapy for a kidney transplant patient with mUC.Case presentationA 71-year-old woman who received a kidney transplant in 2003 was diagnosed with urothelial carcinoma in 2018. After operation of the tumor, the patient developed local recurrence at the site of the right kidney and bladder and multiple distant metastases in May 2020. Considering the intolerance of chemotherapy and high tumor mutation burden, we administered the anti-PD-1 agent tislelizumab (200 mg every three weeks). Partial response was achieved after two cycles of therapy and sustained until 18th cycles. There were no signs of kidney graft rejection. The immunotherapy was temporarily stopped after the 18th course because of a suspicious immune-related pneumonitis and was continued in December 2021.ConclusionsThis case demonstrates the feasibility of safely achieving stable cancer control in a kidney transplant patient with mUC without encountering graft rejection by using single-agent anti-PD-1 treatment.

Sequential Vaccination Against Streptococcus pneumoniae Appears as Immunologically Safe in Clinically Stable Kidney Transplant Recipients

Sequential Vaccination Against Streptococcus pneumoniae Appears as Immunologically Safe in Clinically Stable Kidney Transplant Recipients

Neighborhood Socioeconomic Deprivation is Associated with Worse Outcomes in Pediatric Kidney Transplant Recipients.

Social determinants of health shape a child's transplant course. We describe the association between neighborhood socioeconomic deprivation, transplant characteristics, and graft survival in US pediatric kidney transplant recipients. US recipients <18 years of age at listing transplanted January 1st, 2010, to May 31st, 2022 (N=9,178) were included from the Scientific Registry of Transplant Recipients. Recipients were stratified into three groups according to Material Community Deprivation Index score, with greater score representing higher neighborhood socioeconomic deprivation. Outcomes were modeled using multivariable logistic regression and Cox proportional hazards models. Twenty-four percent (N=110) of recipients from neighborhoods of high socioeconomic deprivation identified as being of Black race, versus 12% (N=383) of recipients from neighborhoods of low socioeconomic deprivation. Neighborhoods of high socioeconomic deprivation had a much greater proportion of recipients identifying as being of Hispanic ethnicity (67%, N=311), versus neighborhoods of low socioeconomic deprivation (17%, N=562). The hazard of graft loss was 55% higher (aHR 1.55, 95% CI: 1.24, 1.94) for recipients from neighborhoods of high versus recipients from low socioeconomic deprivation neighborhoods when adjusted for base covariates, race and ethnicity, and insurance status, with 59% lower odds (aOR 0.41, 95% CI: 0.30, 0.56) of living donor transplantation and, although not statistically significant, 8% lower odds (aOR 0.92, 95% CI: 0.72, 1.19) of preemptive transplantation. The hazard of graft loss was 41% higher (aHR 1.41, 95% CI: 1.25, 1.60) for recipients from neighborhoods of intermediate versus recipients from low socioeconomic deprivation neighborhoods when adjusted for base covariates, race and ethnicity, and insurance status, with 27% lower odds (aOR 0.73, 95% CI: 0.66, 0.81) of living donor transplantation and 11% lower odds (aOR 0.89, 95% CI: 0.80, 0.99) of preemptive transplantation. Children from neighborhoods of high socioeconomic deprivation have worse graft survival and lower utilization of preemptive and living donor transplantation. These findings demonstrate inequities in pediatric kidney transplantation that warrant further intervention.

Use of Direct Anticoagulants in Kidney Transplant Recipients: Review of the Current Evidence and Emerging Perspectives.

Thromboembolic events and atrial fibrillation are common among kidney transplant recipients (KTRs), and these conditions typically require anticoagulation. Traditionally, vitamin K antagonists were used for management, but the use of direct oral anticoagulants (DOACs) has increased in KTRs. In the general population, DOACs are recommended over warfarin, but the applicability of these recommendations to KTRs is unclear because of risk-benefit concerns. There is some hesitancy to use DOACs in KTRs because of their dependence on renal clearance for elimination, potential drug-drug interactions, and limited data. To date, studies of DOACs in KTRs have demonstrated that they are efficient in thromboembolic events, major bleeding is rare, and drug-drug interactions appear rare. However, no guidance yet exists about the use of DOACs, reversal of DOAC action, and the pre- and post-kidney transplant management of DOACs in KTRs, and the evidence base is scarce. Thus, decisions on DOAC use in KTRs are based on expert opinion and the resources and experiences of individual transplant centers. This review summarizes 10 published studies on the use of DOACs in 741 KTRs, evaluating the side effects, efficacy, drug-drug interactions, and perioperative management compared with those of 1320 KTRs using vitamin K antagonists. Although current data are limited, DOACs appear to be relatively safe and effective in KTRs, with some studies suggesting lower bleeding rates and better kidney function than with vitamin K antagonists. However, more research with larger patient groups is needed to draw definitive conclusions.

Determination of Bone Fracture Risk in Kidney Transplant Recipients With FRAX Score

Background:It is thought that the Fracture Risk Assessment Tool(FRAX) score of the World Health Organization determines a 10-year fracture risk.The study aimed to investigate the major osteoporotic fracture(MOF) and hip fracture(HF) values determined with the FRAX score and practicality of the FRAX score in kidney transplant recipients(KTRs).Methods:The study was conducted with 44 female and 59 male KTRs and 100 healty control group.Bone mineral density(BMD) was measured by dual-energy X-ray absorptiometry.FRAX scores were calculated from baseline information (age, height, weight, BMD femur neck T score,previous fracture history, glucocorticoid use, smoking status, alcohol consumption,and presence of rheumatoid arthritis).Results:In KTRs, FRAX score MOF, and FRAX score HF were found to be significantly elevated, while BMD femur T score was determined to be significantly low. No significant relationship was found between FRAX score MOF and HF and kidney function tests and bone parameters. In the ROC analysis performed based on the determination of the FRAX score the cutoff point was determined as≥3.4 for MOF and≥0.4 for HF.Conclusion:In KTRs, increased FRAX score MOF and HF compared to healthy individuals were determined.FRAX score MOF≥3.4 and HF≥0.4 values indicate high-risk patients for increased fracture risk.The high accuracy rates determined suggest that the use of the FRAX score in KTRs is a valuable method for determining fracture risk.