Kidney Recipients Research Articles

Donor Time to Death and Kidney Transplant Outcomes in the Setting of a 3-Hour Minimum Wait Policy.

Lengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time. To assess whether time to death (TTD) from withdrawal of life-sustaining treatment (WLST) is associated with kidney transplant outcomes. This population-based cohort study used data from the prospectively maintained UK Transplant Registry from all 23 UK kidney transplant centers from January 1, 2013, to December 31, 2021; follow-up was until the date of data extraction (October 2023). Participants comprised 7183 adult recipients of DCD kidney-alone transplants. Duration of TTD, defined as time from WLST to donor mechanical asystole. Primary outcome was 12-month estimated glomerular filtration rate (eGFR; for the main eGFR model, variables with significant right skew [histogram visual assessment] were analyzed on the log2 scale), with secondary outcomes of delayed graft function and graft survival (censored at death or 5 years). This study included 7183 kidney transplant recipients (median age, 56 years [IQR, 47-64 years]; 4666 men [65.0%]). Median donor age was 55 years (IQR, 44-63 years). Median TTD was 15 minutes (range, 0-407 minutes), with 885 kidneys transplanted from donors with TTD over 1 hour and 303 kidneys transplanted from donors with TTD over 2 hours. Donor TTD was not associated with recipient 12-month eGFR on adjusted linear regression (change per doubling of TTD, -0.25; 95% CI, -0.68 to 0.19; P = .27), nor with delayed graft function (adjusted odds ratio, 1.01; 95% CI, 0.97-1.06; P = .65) or graft survival (adjusted hazard ratio, 1.00; 95% CI, 0.95-1.07; P = .92). These findings were confirmed with restricted cubic spline models (assessing nonlinear associations) and tests of interaction (including normothermic regional perfusion). In contrast, donor asystolic time, cold ischemic time, and reperfusion time were independently associated with outcomes. Compared with a theoretical 1-hour maximum wait time, the UK policy (minimum 3-hour wait time) has been associated with 885 extra DCD transplants compared with 6298 transplants (14.1% increase). In this cohort study of DCD kidney recipients, donor TTD was not associated with posttransplant outcomes, in contrast to subsequent ischemic times. Altering international transplant practice to mandate minimum 3-hour donor wait times could substantially increase numbers of kidney transplants performed without prejudicing outcomes.

Rise of a CD27- IgD- CD11c+ B cells population in kidney recipients achieving long-term graft stability under immunosuppression.

The use of immunosuppressive treatment is required to prevent rejection events, even a long time after kidney transplantation despite rare recipients achieving long-term graft stability without the need for immunosuppressive treatment, called operationally tolerant patients (TOLs). We comprehensively investigate the immune system of long-term IS recipients (LTTs) and TOLs to highlight their shared and unique immune features. Blood immune cell phenotyping was performed by spectral cytometry. Samples from 34 individuals were analyzed, including 6 LTTs, 8 TOLs, 10 stable patients at 1 year posttransplantation (STAs), and 10 healthy volunteers. B cells differed between LTTs and TOLs with a decreased total B-cell frequency and the acquisition of a memory phenotype in LTTs whereas a naive phenotype is maintained in TOLs. The frequencies of IgD-CD27- B cells and CD11c+ memory B cells are increased in LTTs, with an exhausted phenotype, evoked by a significant decrease in CD25 expression. These CD11c+ B cells display an exhausted phenotype similar to those found in several chronic immune diseases in which they have been shown to participate in their pathophysiology, suggesting active chronic inflammation in LTTs. Altogether, these data indicate that precautions should be taken to minimize IS use.

Suspicious of Acute Kidney Graft Rejection: Tacrolimus Pharmacokinetics Under Methylprednisolone Therapy.

Acute rejection remains one of the main complications in the first months after transplantation and may influence long-term outcomes. Tacrolimus has proven its usefulness in solid organ transplants and its monitoring through the application of pharmacokinetic concepts to optimize individual drug therapy. This research proposes to evaluate the tacrolimus pharmacokinetic parameters in patients suspected of acute kidney graft rejection under methylprednisolone pulse therapy. Eleven adult tacrolimus-treated renal recipients were selected from a prospective, single-arm, single-center cohort study, with suspicion of acute rejection although in use of methylprednisolone pulses therapy. They were followed up for three months posttransplantation, being tacrolimus trough serum concentrations determined using a chemiluminescent magnetic immunoassay, and pharmacokinetic parameters were estimated by using a nonlinear mixed-effects model implemented by Monolix 2020R1. A tacrolimus trough serum concentration range of 8 to 12 ng.mL-1 was considered therapeutic. Six patients showed acute cellular rejection, and two of them in addition had an antibody- mediated rejection. Tacrolimus trough serum concentration was below the reference range in eight patients. Most patients showed a high tacrolimus concentration intrapatient and pharmacokinetic parameters variability. The obtained pharmacokinetics parameters helped in understanding the kidney recipient patients' tacrolimus behavior, assisting in the improvement of individual drug therapy and reducing the risk of acute rejection episodes.

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.

Clinician Prediction of Early Readmission Among Kidney and Liver Transplant Recipients.

Introduction: Patients are at risk of hospital readmission after kidney and liver transplantation due to the complexity of posttransplant care. Currently, clinical practice relies on providers' prediction since there is a lack of specific strategies. However, the accuracy of clinicians' ability to predict readmissions using clinical judgment alone is unknown. Research Question: What is the accuracy of clinicians' ability to predict readmissions after transplantation using clinical judgment alone? Design: In 2019, clinical providers at a large, urban transplant center were electronically surveyed. Primary surgeons, nephrologists, transplant pharmacists, hepatologists, and nurses were asked, within 24 h of any kidney or liver transplant recipient discharge, to predict whether a patient would be readmitted within 30 days, and the suspected causes of readmission. Prediction accuracy was assessed by sensitivity, specificity, positive and negative predictive value, and F-score. Kappa scores were calculated to assess agreement between transplant surgeons and other providers. Results: Overall, N = 34 unique providers were surveyed about 148 kidney and 63 liver transplant recipients, and 27.0% of kidney recipients and 25.4% of liver recipients were readmitted within 30 days. The positive predictive values were low among clinical providers, ranging from 0.25 to 0.55. Agreements between providers were weak, but higher among kidney transplant providers (range: 0.42-0.44) than for liver transplant providers (range: -0.02-0.26). Conclusion: Clinical judgment alone to predict readmission among transplant recipients may not be sufficient and a combination of clinicians' predictions, multitiered discharge surveillance strategies and data-based predictive models may better identify high-risk patients and guide interventions to reduce readmission.

Tremor after solid organ transplantation: Results from the TransplantLines Biobank and Cohort Study.

Tremor is a frequent complaint of solid organ transplant recipients. We report on the largest population investigated with clinical neurophysiological methods. Our aim is to objectively establish the tremor prevalence and syndrome in the largest population of solid organ transplant recipients. Tremor was measured in heart, kidney, liver, and lung recipients, using accelerometers during rest, postural, and weight-loaded conditions. The 95th percentile of healthy kidney donors' tremor amplitude was used as the cutoff to determine the presence of tremor in transplant recipients. Tremor frequency, frequency variability, and effect of loading were used to investigate enhanced physiological tremor as the likely tremor syndrome. Impact on activities of daily life was assessed, and correlations with tacrolimus blood levels were investigated. Tremor was present in 52% of 246 transplant recipients, typically in postural positions. Mean tremor frequency was 6.1 (±2.0) Hz; mean tremor variability was 2.6 (±1.8) Hz. A frequency decrease upon loading was found in 83% of patients with tremor. Sixty-five percent of patients met formal clinical neurophysiological criteria for enhanced physiological tremor. Tremor-related impairment was present in 55% and correlated with tremor amplitude (ρ = 0.23, p ≤ 0.001). In a binominal regression analysis, tacrolimus blood levels were independently associated with tremor prevalence (p = 0.009). More than half of solid organ transplant recipients experience a tremor that best fits the syndrome of enhanced physiological tremor. This is the first objective study on tremor that has established a better understanding of the neurophysiological mechanisms of tremor in a large population of solid organ transplant recipients.

Archetypal Analysis of Kidney Allograft Biopsies Using Next-generation Sequencing Technology.

In kidney transplantation, molecular diagnostics may be a valuable approach to improve the precision of the diagnosis. Using next-generation sequencing (NGS), we aimed to identify clinically relevant archetypes. We conducted an Illumina bulk RNA sequencing on 770 kidney biopsies (540 kidney recipients) collected between 2006 and 2021 from 11 European centers. Differentially expressed genes were determined for 11 Banff lesions. An ElasticNet model was used for feature selection, and 4 machine learning classifiers were trained to predict the probability of presence of the lesions. NGS-based classifiers were used in an unsupervised archetypal analysis to different archetypes. The association of the archetypes with allograft survival was assessed using the iBox risk prediction score. The ElasticNet feature selection reduced the number of the genes from a range of 859-10 830 to a range of 52-867 genes. NGS-based classifiers demonstrated robust performances (precision-recall area under the curves 0.708-0.980) in predicting the Banff lesions. Archetypal analysis revealed 8 distinct phenotypes, each characterized by distinct clinical, immunological, and histological features. Although the archetypes confirmed the well-defined Banff rejection phenotypes for T cell-mediated rejection and antibody-mediated rejection, equivocal histologic antibody-mediated rejection, and borderline diagnoses were reclassified into different archetypes based on their molecular signatures. The 8 NGS-based archetypes displayed distinct allograft survival profiles with incremental graft loss rates between archetypes, ranging from 90% to 56% rates 7 y after evaluation (P < 0.0001). Using molecular phenotyping, 8 archetypes were identified. These NGS-based archetypes might improve disease characterization, reclassify ambiguous Banff diagnoses, and enable patient-specific risk stratification.

Promising Results of Kidney Transplantation From Donors Following Euthanasia During 10-Year Follow-Up: A Nationwide Cohort Study.

The outcome of kidneys transplanted following organ donation after euthanasia (ODE) remains unclear. This study analyzed all kidney transplantations in the Netherlands from January 2012 to December 2021, comparing the outcomes following ODE, donation after circulatory death (DCD-III), and donation after brain death (DBD). 9,208 kidney transplantations were performed: 148 ODE, 2118 DCD-III, and 1845 DBD. Initial graft function was compared between these categories. Immediate graft function, delayed graft function and primary non-function in ODE kidney recipients were 76%, 22%, and 2%, respectively, 47%, 50% and 3% in DCD-III kidney recipients and 73%, 25%, and 2% in DBD kidney recipients (overall p-value: p < 0.001). The number of kidneys transplanted over a median follow-up period of 4.0 years (IQR 2.0-6.6), was 1810, including 72 ODE, 958 DCD-III and 780 DBD kidneys. In this period, 213 grafts (11.8%) failed [7 grafts (9.7%) from ODE donors, 93 grafts (9.7%) from DCD-III donors, and 113 grafts (14.5%) from DBD donors]. Kidneys transplanted after euthanasia have a good immediate graft function, a comparable longitudinal 10years eGFR, and similar graft failure hazard to kidneys from DCD-III and DBD. Kidney transplantation following ODE is a valuable and safe contribution to the donor pool.

Safety of Kidney Transplantation from Donors with HIV

BackgroundKidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls.MethodsIn an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection.ResultsWe enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment.ConclusionsIn this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.)

Area-Level Social Deprivation and Cytomegalovirus Seropositivity at the Time of Solid Organ Transplant

Cytomegalovirus (CMV) is associated with significant morbidity and mortality in solid organ transplant (SOT) recipients. The risk factors for CMV seropositivity in SOT recipients, including area-level social deprivation in the US, have not been fully characterized. To (1) evaluate CMV seroprevalence, (2) assess the recipient characteristics associated with CMV seropositivity, and (3) assess the association of area-level social deprivation index (SDI) scores with pretransplant CMV serostatus. This retrospective cross-sectional analysis of the Scientific Registry of Transplant Recipients database included all adult (aged ≥18 years) SOT recipients from January 1, 2008, to May 31, 2022. Data were analyzed from April 10 to October 25, 2023. Recipient characteristics and area-level SDI. Multivariable generalized linear models were used to evaluate the association between (1) patient characteristics and CMV and (2) social deprivation (measured by SDI scores, which were assessed in quintiles, from lowest to highest) and CMV seropositivity. In addition, differences based on patient demographics and the transplanted organ(s) were evaluated. Among the 389 288 SOT recipients included in the analysis, mean (SD) age was 53.3 (13.0) years; 63.0% were male, 21.4% were Black, 15.2% were Hispanic White, 56.2% were non-Hispanic White, and 62.7% were CMV seropositive. The mean (SD) age was higher among CMV seropositive (54.0 [12.7] years) compared with CMV seronegative (52.0 [13.5] years) patients. Seropositivity for CMV was higher among women (69.9%) than men (58.5%) and among Black (74.8%) and Hispanic White (80.2%) patients compared with non-Hispanic White patients (50.4%). Seropositivity for CMV was highest among kidney (64.5%), liver (63.6%), and kidney and liver (66.2%) recipients. Greater SDI scores were associated with greater CMV seropositivity, ranging from 51.7% for the least deprived to 75.5% for the most deprived quintiles (P < .001), independent of age, sex, or race. In this cross-sectional study, an association between SDI and CMV seropositivity was observed among SOT recipients, independent of age, sex, or race and ethnicity. To optimize posttransplant outcomes in CMV seropositive recipients, efforts targeting prevention of CMV reactivation need to be prioritized in these higher-risk populations.

Effect of cholecalciferol supplementation on PTH and increasing the glomerular filtration rate in kidney transplant patients at King Faisal Specialist Hospital and Research Center

The association between oral cholecalciferol and GFR has been identified in various renal transplant populations around the globe. This study aimed to evaluate the effect of oral cholecalciferol supplementation on the GFR and serum PTH levels, with other parameters in the Saudi kidney transplant population. A retrospective observational study was conducted on a cohort of 174 kidney recipients who underwent transplantation and had serum 25-Hydroxy VD level tests performed (2018-2022) at King Faisal Specialist Hospital and Research Center in Jeddah, KSA. Generalized and linear mixed effects regression models were conducted. The percentage of GFR &gt;60 (25.86% vs 78.16%, P&lt;.0001) and VD insufficiency (&lt; 30 ng/mL) (36.21% vs 6.90%, P&lt;.0001) were significantly different between pre-&amp; post-transplant periods, respectively. After adjustment, significant changes were found in post-transplant GFR, hemoglobin levels, serum creatinine levels, blood urea nitrogen levels, hematocrit levels, PTH levels, and VD 25-Hydroxy from the baseline. Calciferol 1000/2000 IU and 50,000 IU (P&lt;.0001) were significantly more effective in increasing the odds of having GFR &gt;60 as compared to other supplements (P=0.75). VD supplementations may be particularly beneficial in improving kidney function in kidney transplant patients, as this contributes to normalizing GFR levels and creatinine levels and reducing PTH levels.

Pretransplantation assessment of BK virus seropositivity in kidney donors and recipients

Background: BK virus (BKV) is a member of the polyomavirus family. The determination of anti-BKV immunoglobulin G (IgG) antibody levels in kidney donors and recipients has been reported as a possible predictor of the risk of BK nephropathy. Allograft dysfunction is a significant risk factor. The main objective of this study was to address the high prevalence of renal failure due to BKV nephropathy in kidney transplant recipients. This investigation aims to determine whether donors and recipients of renal transplants had BKV IgG antibodies before transplantation. Methods: Blood samples were collected from 46 kidney transplant recipients and their corresponding 46 donors. An enzyme-linked immunosorbent assay was used to qualitatively analyze human BKV IgG. Results: Ninety-two participants, 46 kidney transplant donors, and 46 kidney transplant recipients, were analyzed. Pretransplantation anti-BKV antibody levels were higher in kidney transplant donors (73%) than in recipients (63%). Donors and recipients included in the study were grouped into seropositive and seronegative recipients, with the highest proportion of seropositive recipient-donor groups (48%) and the lowest percentages in the seronegative donor and seronegative recipient groups. Fifty-one percent of the participants were male and 49% were female. The age distribution of most subjects was &gt;50 years old. Conclusion: BKV can cause kidney transplant rejection. Routine screening of transplant recipients and donors for BKV IgG seropositivity is recommended before renal transplantation. This can improve transplant outcomes and prevent rejection.

Reexamining Transplant Outcomes in Acute Kidney Injury Kidneys Through Machine Learning.

Despite many people awaiting kidney transplant, kidney allografts from acute kidney injury (AKI) donors continue to be underutilized. We aimed to cluster kidney transplant recipients of AKI kidney allografts using an unsupervised machine learning (ML) approach. Using Organ Procurement and Transplantation Network-United Network for Organ Sharing (OPTN/UNOS) data, a consensus clustering cohort analysis was performed in 12356 deceased donor kidney transplant recipients between 2015 and 2019 in whom donors had a terminal serum creatinine ≥1.5mg/dL. Significant cluster characteristics were determined, and outcomes were compared. The median donor terminal creatinine was 2.2 (interquartile range [IQR] 1.7-3.3) mg/dL. Cluster analysis was performed on 12356 AKI kidney recipients, and three clinically distinct clusters were identified. Young, sensitized kidney re-transplant patients characterized Cluster 1. Cluster 2 was characterized by first-time kidney transplant patients with hypertensive and diabetic kidney diseases. Older diabetic recipients characterized Cluster 3. Clusters 1 and 2 donors were young and met standard kidney donor profile index (KDPI) criteria; Cluster 3 donors were older, more likely to have hypertension or diabetes, and meet high KDPI criteria. Cluster 1 had a higher risk of acute rejection, 3-year patient death, and graft failure. Cluster 3 had a higher risk of death-censored graft failure, patient death, and graft failure at 1 and 3 years. Cluster 2 had the best patient-, graft-, and death-censored graft survival at 1 and 3 years. Compared to non-AKI kidney recipients, the AKI clusters showed a higher incidence of delayed graft function (DGF, AKI: 43.2%, 41.7%, 45.3% vs. non-AKI: 25.5%); however, there were comparable long-term outcomes specific to death-censored graft survival (AKI: 93.6%, 93.4%, 90.4% vs. non-AKI: 92.3%), patient survival (AKI: 89.1%, 93.2%, 84.2% vs. non-AKI: 91.2%), and overall graft survival (AKI: 84.7%, 88.2%, 79.0% vs. non-AKI: 86.0%). In this unsupervised ML approach study, AKI recipient clusters demonstrated differing, but good clinical outcomes, suggesting opportunities for transplant centers to incrementally increase kidney utilization from AKI donors.

Delayed Graft Function Equally Worsens Early Outcomes in Kidney Recipients from Donation after Circulatory Death vs. Brain Death Donors

Delayed Graft Function Equally Worsens Early Outcomes in Kidney Recipients from Donation after Circulatory Death vs. Brain Death Donors

Risk of Post-transplantation Hepatocellular Carcinoma, Cirrhosis, and Liver Failure in Kidney Recipients with Hepatitis C Infection

Risk of Post-transplantation Hepatocellular Carcinoma, Cirrhosis, and Liver Failure in Kidney Recipients with Hepatitis C Infection

The burden of COVID-19 mortality among solid organ transplant recipients in the United States

Solid organ transplant recipients (SOTRs) have heightened risk of adverse COVID-19 outcomes due to immunosuppression and medical comorbidity. We quantified the burden of COVID-19 mortality in US SOTRs. A sample of deaths documented in the US solid organ transplant registry from June 2020 through December 2022 were linked to the National Death Index to identify COVID-19 deaths and weighted to represent all SOTR deaths during the study period. Among 505,757 SOTRs, 57,575 deaths occurred and based on the linkage, 12,396 (21.5%) were due to COVID-19. COVID-19 mortality was higher in males (mortality rate ratio [MRR]: 1.13), SOTRs aged 65 and older (MRR: 1.50 in ages 65–74 vs. ages 55–64), and non-Hispanic Black and Hispanic SOTRs (MRRs: 1.55 and 1.79 vs. non-Hispanic White SOTRs). Kidney and lung recipients had the highest COVID-19 mortality, followed by heart, then liver recipients. COVID-19 mortality also varied over time and across US states. Overall, SOTRs had 7-fold increased risk of COVID-19 death compared to the US general population. SOTRs comprised 0.13% of the US population but accounted for 1.46% of all US COVID-19 deaths. SOTRs experience greatly elevated COVID-19 mortality. Clinicians should continue to prioritize COVID-19 prevention and treatment in this high-risk population.

Association of Donor Vascular Endothelial Growth Factor Gene Polymorphism With Acute Renal Allograft Rejection.

Recipient's VEGF-A polymorphisms have been reported to be associated with the risk of acute allograft rejection. However, an association of the donor's VEGF-A gene polymorphism with rejection remained unelucidated till now. In this study, VEGF-A gene SNPs at nine loci were analyzed in 160 kidney donors and recipients with rejection (rejectors, n=80) and without rejection (non-rejectors, n=80). Blood VEGF-A mRNA, plasma VEGF level, and intragraft VEGF expression were also analyzed by RT-PCR, ELISA, and immunohistochemistry, respectively. On comparing between the donor and rejectors, the polymorphic genotypes of VEGF -634 C>G [GG genotype, p<0.0001; OR (95% CI) = 17.74 (5.16-60.96)]; VEGF -1154 G>A [AG genotype, p<0.0001, OR (95% CI)=16.07 (3.68-70.15)]; VEGF +936 C>T [CT genotype, p<0.0001, OR (95% CI)=178.64 (23.28-1370.9), and TT genotype, p<0.0001; OR (95% CI)=3149 (278.91-35553)]; VEGF -1455 T>C [CC genotype, p value=0.0464, OR (95% CI) = 3.13 (1.07-9.10)]; VEGF -2578 C>A [CA genotype, p=0.0426, OR (95% CI)=4.62 (1.03-20.59), and AA genotype, p value<0.0001, OR (95% CI) = 21.89 (4.94-97.04)]; VEGF -2549 18bp Insertion/Deletion [ID genotype, p value<0.0001, OR (95% CI)=27.27 (3.61-205.73) and DD genotype, p value<0.0001, OR (95% CI)=25.18 (3.30-191.89) were significantly associated with acute rejection risk. On comparing rejectors versus non-rejectors, GA genotype of VEGF -1190 G>A and TC genotype of VEGF -1455 T>C were associated with the risk of rejection. On comparing donor VEGF between rejectors and non-rejectors, CG genotype of VEGF -634 C>G, AG of VEGF -1154 G>A; GA of VEGF -1190 G>A were associated with rejection. The blood VEGF-A mRNA and plasma VEGF levels were higher in the rejectors group compared to non-rejectors. Besides the recipient's VEGF SNPS, the donor's VEGF SNPs are also associated with the risk of acute rejection and may be closely monitored in evaluation to determine the risk of rejection.

Posttransplant Lymphoproliferative Disorder in Pediatric Solid-Organ Transplant Recipients: A 7-Year Single-Center Analysis.

Posttransplant lymphoproliferative disorder is a consequential complication following solid-organ transplant, particularly associated with the Epstein-Barr virus. We studied a single center's cases of pediatric posttransplant lymphoproliferative disorder for a 7-year period and focused on incidence rates, anatomic sites involved, and correlation with clinical outcomes. We explored clinical features and treatment outcomes in patients with pediatric posttransplant lymphoproliferative disorder, with emphasis on patient survival and associated clinical ramifications. This was a retrospective analysis of medical records from pediatric solid-organ transplant recipients (liver or kidney) at Baskent University Ankara Hospital Organ Transplantation Center between January 1, 2017, and January 1, 2024, approved by the Institutional Review Board (KA24/63). We identified cases based on pathology-confirmed persistent lymphadenopathy or tumorous lesions. Patient categorization distinguished between malignant and benign groups. Early posttransplant lymphoproliferative disorder was defined within the initial year after transplant. Epstein?Barr virus association was determined through in situ hybridization, and patient characteristics were reviewed comprehensively. In 7 years, 10 pediatric patients (9 liver transplants, 1 kidney transplant) were diagnosed with posttransplant lymphoproliferative disorder, with an incidence of 8.7% for pediatric liver transplants. Mean age at diagnosis was 46.4 months, and mean time from transplant to diagnosis was 21.2 months. The most common complaints at diagnosis included fever, lymphadenopathy, hepatosplenomegaly, dyspnea, and diarrhea. Treatment modalities included rituximab, immunosuppression reduction, intravenous immunoglobulin therapy, and chemotherapy (NHL Berlin-Frankfurt-Münster 90 protocols). All patients achieved remission (mean follow-up, 22.9 mo). Early diagnosis of posttransplant lymphoproliferative disorder is important, and rituximab with immunosuppression reduction is effective to achieve complete remission, particularly in early polymorphic cases. Despite challenges, all patients achieved remission, signaling improved outcomes in pediatric posttransplant lymphoproliferative disorder. Active monitoring of Epstein?Barr virus infection may further reduce posttransplant lymphoproliferative disorder complications in pediatric solid-organ transplant; hence, early diagnosis is crucial.

Urinary Metabolite Constellation Also Detects Very Early Post-transplant Rejection in Living Donor Kidney Recipients

Urinary Metabolite Constellation Also Detects Very Early Post-transplant Rejection in Living Donor Kidney Recipients

Torque Teno Virus Loads as a Marker of Immunosuppression in Pediatric Kidney Transplant Recipients.

Long-term renal function and survival after kidney transplantation rely on appropriate immunosuppressive treatment to prevent the risk of rejection. New biomarkers are needed to accurately assess the degree of immunosuppression in renal transplant recipients in order to avoid organ rejection and the development of opportunistic infections. Highly prevalent in humans, torque teno virus (TTV), which belongs to the family Anelloviridae, is a small, nonenveloped, single-stranded DNA virus which has not been linked with any specific human illness, but which constitutes a major component of the human virome. Host antiviral responses allow TTV levels to be controlled; however, viral persistence remains, explaining the high prevalence in human populations, including healthy individuals. Important confounders of TTV load include time since transplantation, age, gender, obesity, and smoking status. TTV-based guidance of immunosuppressive drug dosing could help with risk stratification, reducing the risk of infection, graft rejection and oncologic disease on an individual level, enabling long-term patient and graft survival. Original studies were accessed by a systematic search from electronic databases including PubMed, ScienceDirect and Wiley Online Library. The presented data mainly derive from adult transplant recipients showing an association between TTV plasma levels and the immune status of the host: High-TTV load and high immunosuppression are associated with a risk of infection, and low-TTV load and low immunosuppression indicate a risk of rejection. However, there is minimal information on pediatric transplant recipients with further research required in this cohort. To date, it has been demonstrated that longer posttransplant times are significantly associated with lower TTV levels in children with renal transplant. Meanwhile, an association between lower TTV loads and increased risk of graft reject during the first year of transplantation was also reported. More recently, Eibensteiner etal. revealed a robust, independent association between TTV plasma load and the onset of Cytomegalovirus and BK virus infections. Data from randomized controlled trials are still missing, even in adults, but a multicenter randomized controlled trial for TTV-guided immunosuppression in adult kidney recipients (TTVguideIT) began in 2022. There is, therefore, great promise for TTV levels to be used as a biomarker that could potentially improve both graft and patient survival in transplantation.