High-risk Kidney Research Articles

A comparative study on outcomes of ABO-incompatible kidney transplants between robot-assisted vs. open surgery-propensity score-matched analysis: a retrospective cohort study.

Robot-assisted kidney transplantation (RAKT) is increasingly being adopted worldwide. Despite this growing interest, there remains a notable gap in the literature, especially concerning its effectiveness in immunologically high-risk patients compared to conventional open kidney transplantation (OKT). This study investigates the viability and success of RAKT in comparison with OKT, particularly for recipients with ABO incompatibility (ABOi). This retrospective, single-center study included 239 living-donor transplants between October 2020 and February 2023, with 210 patients undergoing ABOi-OKT and 29 undergoing ABOi-RAKT. A composite of biopsy-proven acute rejection (BPAR), graft failure, and the development of de novo donor-specific antibodies was analyzed through univariate and multivariate models. Propensity score matching (PSM) was utilized to ensure a balanced comparison between the two groups. Following PSM, a total of 131 cases in the OKT group and 26 cases in the RAKT group were analyzed. After PSM, the mean recipient age was 48.56 years for OKT and 47.96 years for RAKT. Both groups had comparable one-year (RAKT: 92.4%, OKT: 93.1%) and two-year BPAR-free survival rates (RAKT: 92.4%, OKT: 91.9%). Mean estimated glomerular filtration rate values were similar at 12 months post-transplant (RAKT: 62.15ml/min/1.73m², OKT: 64.53ml/min/1.73m²). Operative times were significantly longer for RAKT (291.42 vs. 150.81min, p < 0.001), while cold ischemic time was also longer for RAKT (119.77 vs. 47.22min, p < 0.001). Hospital stays were shorter for RAKT (median 6 vs. 8 days, p < 0.001). There was no significant difference in the composite outcome of BPAR, graft failure, and de novo donor-specific antibodies between the two groups (HR 0.858, 95% CI: 0.180-4.096, p = 0.848). RAKT is a safe and effective alternative to OKT in ABOi patients, demonstrating similar perioperative outcomes, graft survival rates, and renal function. The application of ropensity score matching analysis strengthens the reliability of these findings, confirming RAKT's viability for high-risk kidney transplant recipients. The clinical trial associated with this study was registered on 2024-02-24 with the Clinical Trial Number NCT06287008|| https://www. gov/ ).

Characterization of Cytomegalovirus (CMV) Viremia and Disease in CMV High-Risk Kidney Transplant Recipients: A Single-Center Experience

Characterization of Cytomegalovirus (CMV) Viremia and Disease in CMV High-Risk Kidney Transplant Recipients: A Single-Center Experience

Antibody-mediated rejection diagnosed in early protocol biopsies in high immunological risk kidney transplant recipients.

Renal transplant recipients with donor-specific anti-HLA antibodies are at an increased risk of antibody-mediated rejection (AMR). Early protocolized renal biopsies may serve as a strategy to improve diagnosis in this patient population. We evaluated 155 highly sensitized renal transplant recipients with cPRA class I+II>90% pre-transplant from 2015 to 2022. Patients with protocol biopsies within the first two weeks post-transplant were included. A total of 122 patients were included in the study. Of these, 13 (10.6%) were diagnosed with very early antibody-mediated rejection (veABMR) within the first two weeks post-transplant. This corresponds to 52% (13/25 patients) of all ABMR cases reported during the follow-up of this population. The graft survival rates at one and three years were significantly lower in patients with veABMR (p<0.001) compared to patients without rejection in the early protocol biopsy. In terms of severity, the veABMR cohort exhibited a hazard ratio (HR) of 10.33 (95% CI 3.23-33.06; p<0.001) for graft failure. The presence of donor-specific antibodies (DSA) class II on the day of transplantation and a higher percentage of eplet mismatch (EpMM), particularly EpMM DQA1, correlated with the development of veABMR. Early protocol biopsies play a pivotal role in the early detection of veABMR in high-risk immunological patients. Patients with veABMR face significant risks of graft loss, despite early treatment of rejection.

220.3: Outcomes of high immunological risk kidney transplantation in an Asian tertiary academic transplant centre.

220.3: Outcomes of high immunological risk kidney transplantation in an Asian tertiary academic transplant centre.

From Plan to Pivot: How Model-Informed Drug Development Shaped the Dose Strategy of the Zibotentan/Dapagliflozin ZENITH Trials.

Getting the dose right is a key challenge in drug development; model-informed drug development (MIDD) provides powerful tools to shape dose strategies and inform decision making. In this tutorial, the case study of the ZENITH trials showcases how a set of clinical pharmacology and MIDD approaches informed an impactful dose strategy. The endothelin A receptor antagonist zibotentan, combined with the sodium-glucose co-transporter-2 inhibitor dapagliflozin, has yielded a robust and significant albuminuria reduction in the Phase IIb trial ZENITH-CKD and is being investigated for reduction of kidney function decline in a high-risk chronic kidney disease population in the Phase III trial ZENITH High Proteinuria. Endothelin antagonist treatment has, until now, been limited by the class effect fluid retention. ZENITH-CKD investigated a wide range of zibotentan doses based on pharmacokinetics in renal impairment, competitor-data exposure-response modeling, and clinical trial simulations. Recruitment delays reduced interim analysis data availability; here, supportive dose-response modeling recovered decision-making confidence. At trial completion, the low-dose arm enabled Phase III dose selection between Phase IIb doses. Dose-response modeling of efficacy and Kaplan-Meier analyses of tolerability identified a kidney-function-based low-dose strategy of 0.25 or 0.75 mg zibotentan (with 10 mg dapagliflozin) to balance benefit/risk in ZENITH High Proteinuria. The applied clinical pharmacology and MIDD principles enabled successful Phase IIb dose finding, rationalized and built confidence in the innovative Phase III dosing strategy and identified a potential therapeutic window for zibotentan/dapagliflozin, providing the opportunity for a significant improvement in the treatment of chronic kidney disease with high proteinuria.

Cytomegalovirus Post-Prophylaxis Surveillance in High-Risk Kidney and Liver Recipients Prevents CMV End-Organ Disease and Ganciclovir-Resistance.

Evaluate cytomegalovirus (CMV) post-prophylaxis surveillance in high-risk (D+/R-) kidney and liver transplant recipients. Adult D+/R- patients were included if transplanted between 6/1/15 and 11/30/22 and divided into a pre-CMV-stewardship-era (6/1/15-5/31/18), CMV-stewardship-era (6/1/18-6/30/20), and a surveillance-era (7/1/2020-11/30/2022) then followed through 12 months. The primary objective was to evaluate CMV-related outcomes. The secondary objective was to assess graft and patient survival by era. There were 328 patients in the study period; 133 in the pre-stewardship-era, 103 in the stewardship-era, and 92 in the surveillance-era. Replication rates in the surveillance-era were significantly higher, as anticipated due to increased sampling (pre 38.4%, stewardship 33.0%, surveillance 52.2%, p=0.02). Time from transplant to first replication was similar (pre 214.0±79.0 days, stewardship 231.1±65.5, surveillance 234.9±61.4, p=0.29). CMV viral load (VL) at first detection, maximum-VL, and incidence of VL > 100 000 IU/mL were numerically lower in the surveillance era, although not statistically significant. CMV end-organ disease (p < 0.0001) and ganciclovir-resistance (p=0.002) were significantly lower in the surveillance era than in both previous eras. Rejection was not different between eras (p=0.4). Graft (p=0.0007) and patient survival (p=0.008) were significantly improved in the surveillance era. Post-prophylaxis surveillance significantly reduced CMV end-organ disease and resistance. Despite observing increased replication rates in the surveillance era, rejection was not significantly different and there was no graft loss or patient mortality at 12 months.

Cell-mediated Immunity to Guide Primary Prophylaxis for CMV Infection in Organ Transplant Recipients: A Multicenter Single-arm Prospective Study.

There are few interventional studies using CMV cell-mediated immunity (CMI) to guide antiviral prophylaxis. We assessed the Quantiferon-CMV (QTF-CMV) assay to guide CMV prophylaxis duration in high-risk organ transplant recipients. A single-arm, multicenter, prospective interventional study including high-risk kidney, pancreas, liver, and heart transplant recipients who were either donor CMV-seropositive, recipient-seronegative (D+/R-) or recipient-seropositive with antithymocyte globulin (R+/ATG) induction. CMI testing was performed using the QTF-CMV assay at months 3, 4, 5, and 6 posttransplant. Prophylaxis was discontinued for a positive CMI but continued for a negative result up to a maximum of 6 mo. The primary endpoint was CMV viremia ≥1000 IU/mL up to 1 y posttransplant. One hundred eight patients were included, comprising kidney (n = 89), kidney-pancreas (n = 7), liver (n = 10), and heart (n = 2) transplants. Eighty-nine patients (82.4%) completed the study protocol (n = 39 D+/R- and n = 50 R+/ATG). In the D+/R- group, only 1 of 39 patients (2.6%) had a positive QTF-CMV result. In the R+/ATG group, 33 of 50 patients (66%) had a positive QTF-CMV result before 6 mo, allowing for early discontinuation of prophylaxis (28 at month 3, 4 at month 4, and 1 at month 5). During the follow-up, CMV viremia ≥1000 IU/mL occurred in only 4 of 33 patients (12.1%) who discontinued prophylaxis early compared with 6 of 17 patients (35.3%) with negative QTF-CMV results and continued prophylaxis (hazard ratio 0.31; 95% confidence interval, 0.09-1.09; P = 0.07). No R+ patient developed CMV disease. QTF-CMV-guided prophylaxis appears useful in R+ patients who may benefit from a tailored duration of prophylaxis. This strategy does not appear to be useful in D+/R- patients.

Deceased donor kidney function and branched chain amino acid metabolism during ex vivo normothermic perfusion

Current kidney perfusion protocols are not optimized for addressing the ex vivo physiological and metabolic needs of the kidney. Ex vivo normothermic perfusion may be utilized to distinguish high-risk kidneys to determine suitability for transplantation. Here, we assessed the association of tissue metabolic changes with changes in a kidney injury biomarker and functional parameters in eight deceased donor kidneys deemed unsuitable for transplantation during a 12- hour ex vivo normothermic perfusion. The kidneys were grouped into good and poor performers based on blood flow and urine output. The mean age of the deceased kidney donors was 43 years with an average cold ischemia time of 37 hours. Urine output and creatinine clearance progressively increased and peaked at six hours post-perfusion among good performers. Poor performers had 71 ng/ml greater (95% confidence interval 1.5, 140) urinary neutrophil gelatinase-associated lipocalin at six hours compared to good performers corresponding to peak functional differences. Organ performance was distinguished by tissue metabolic differences in branched chain amino acid metabolism and that their tissue levels negatively correlated with urine output among all kidneys at six hours. Tissue lipid profiling showed poor performers were highlighted by the accumulation of membrane structure components including glycerolipids and sphingolipids at early perfusion time points. Thus, we showed that six hours is needed for kidney function recovery during ex vivo normothermic perfusion and that branched chain amino acid metabolism may be a major determinant of organ function and resilience.

An overview of the CANVAS Program and CREDENCE trial: The primary outcomes and key clinical implications for those managing patients with type 2 diabetes.

To provide an overview of the primary outcomes and key clinical implications of the CANVAS Program and CREDENCE trial, which were event-driven, double-blind randomized controlled trials that established the efficacy and safety of canagliflozin in those with type 2 diabetes (T2D) and high cardiovascular risk (CV) or albuminuric chronic kidney disease (CKD). The CANVAS programme (CANVAS and CANVAS-R trials) randomized 10 142 people with T2D and high CV risk to canagliflozin or placebo and followed them for a median of 126 weeks. The primary efficacy outcome was met, with canagliflozin treatment associated with a 14% reduction in major adverse CV events (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75 to 0.97; p < 0.001) as compared to placebo. The CREDENCE trial randomized 4401 individuals with T2D and albuminuric CKD to canagliflozin or placebo and followed them for 109 weeks. The CREDENCE trial also met its primary endpoint; canagliflozin treatment was associated with a 30% reduction in the composite of kidney failure, sustained doubling of serum creatinine level, or death from kidney or CV causes (HR 0.70, 95% CI 0.59 to 0.82; p < 0.001). Substantial reductions in hospitalization for heart failure (CANVAS: HR 0.67, 95% CI 0.52 to 0.87; CREDENCE: HR 0.61, 95% CI 0.47 to 0.80) and other key CV and kidney outcomes were also identified. Relative clinical benefits were consistent across subgroups defined by baseline age, sex, kidney function and history of CV disease but absolute benefits were greatest in those at highest baseline risk. Total serious adverse events were less common with canagliflozin treatment. Concerns about amputation and fracture risk observed in the CANVAS Program were not seen in CREDENCE and appear to have been spurious chance findings. Canagliflozin reduced important CV, kidney and mortality outcomes in those with T2D and high CV risk or CKD across diverse patient groups, with a good safety profile. Taken together with the other sodium-glucose cotransporter-2 inhibitor CV and renal outcomes trials, these landmark findings have changed the treatment landscape for patients worldwide.

#3052 mTOR inhibitors in kidney transplant recipients with high immunological risk: practical insights from clinical experience

Abstract Background and Aims The use of mTOR inhibitors (mTORi) is not usually considered in high immunological risk kidney transplant recipients (KTR) for a perceived increased risk of rejection. However, in most of the studies that examined the combination of mTORi with calcineurin inhibitors (CNI), hypersensitized patients have been excluded from enrollment. The aim of the present study is to analyze our clinical experience with the use of mTORi in association with calcineurin inhibitors (CNI) in this subset of patients. Method Analysis of 212 consecutive kidney transplant recipients with a baseline calculated panel reactive antibody (cPRA) ≥50% who received a graft from June 2013 to December 2019. Immunosuppression was based on tacrolimus, steroids and, alternatively, mycophenolic acid (MPA; n = 96) or mTORi (either sirolimus or everolimus, target trough levels 3-8 ng/ml, n = 116) depending on the active Institution's protocol at the time of transplantation. The outcomes chosen included rejection-free, graft and patient survival and were analyzed by means of Cox-regression analysis. Results Demographic and immunological characteristics were similar between groups, apart from the higher number of living donors in the MPA group (42.7% vs 14.7%%, P &amp;lt; 0.001). Baseline cPRA was 92.5 [76-98]% for the MPA and 94 [77.25-98]% for the mTORi group, respectively (P = 0.882). Induction therapy with lymphocyte-depleting agents was employed in the majority of patients (91.7% in the MPA group and 88.8% in the mTORi group, P = 0.898). Median follow-up time was 2.6 [1.45-4.05] years. Biopsy-proven rejection (either cellular or humoral) occurred in 33.3% of the MPA and in 19.8% of the mTORi group, respectively. Cox-regression analysis of rejection-free survival revealed better rejection-free survival with mTORi versus MPA (HR [95% CI], 0.54 [0.32-0.98], P = 0.028). The only other baseline factor associated with rejection was previous transplantation (HR [95% CI] 1.96 [1.07-3.60], P = 0.030). When entered into a bivariable Cox-regression analysis, both mTORi and previous transplantation maintained a statistical significant association with rejection (mTORi versus MPA HR [95% CI] 0.53 [0.31-0.91], P = 0.023, and previous transplantation HR [95% CI] 2.01 [1.09-3.69], P = 0.024). No differences between mTORi and MPA were noted for graft (HR [95% CI] 0.90 [0.40-2.02], P = 0.807) and patient survival (HR [95% CI] 1.23 [0.60-2.50, P = 0.606). Median creatinine 1 year after transplantation was 1.45 [1.11-1.98]mg/dl for the MPA group and 1.51 [1.09-2.06]mg/dl for the mTORi group (P = 0.917). Conclusion This retrospective study suggests that hypersensitized KTRs can receive safely a maintenance immunosuppression based on a combination of CNI with mTORi, without an increased risk of rejection.

Real-life use of letermovir prophylaxis for cytomegalovirus in heart transplant recipients.

Cytomegalovirus (CMV) remains the predominant opportunistic infection following solid organ transplantation (SOT). While valganciclovir is the drug of choice for CMV prophylaxis, its utility can be compromised due to the risk of cytopenia. Letermovir, a novel agent approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients and high-risk kidney transplant recipients, exhibits reduced toxicity. This study aims to present the practical application of letermovir as both primary and secondary prophylaxis against CMV in heart transplant recipients (HTR). In this observational, retrospective, single-center study, we included all consecutive adult HTRs from June 2020 to January 2022 who were administered letermovir for CMV prophylaxis. We documented instances of CMV breakthrough infections, side effects related to letermovir, changes in neutropenia following the switch from valganciclovir to letermovir, and any drug interactions with the immunosuppressive regimen. The study comprised 10 patients: two received primary prophylaxis with letermovir due to a high risk of CMV infection (donor-positive, recipient-negative serostatus), and eight received it as secondary prophylaxis following a CMV infection. The median duration of letermovir administration was 8 months (range 3-12 months). No CMV breakthrough infections were reported while on prophylaxis. However, three patients experienced CMV breakthrough infections after discontinuing letermovir prophylaxis (30%). No significant side effects were observed, although one patient reported digestive intolerance. Among the nine patients on tacrolimus, six needed reduced doses after switching to letermovir. This real-life study appears to support the effectiveness of letermovir prophylaxis in HTR. Nonetheless, the risk of CMV infection post-treatment cessation is notable. Further drug monitoring and research on the efficacy of letermovir for CMV prophylaxis in SOT patients is warranted.

Letermovir safety and efficacy for cytomegalovirus prophylaxis in adult Japanese kidney transplant recipients: a multicenter, open-label, noncomparative Phase 3 study

BackgroundLetermovir is approved for cytomegalovirus (CMV) prophylaxis in adult allogeneic hematopoietic cell transplantation recipients worldwide and is also approved in the United States for CMV prophylaxis in adult high-risk (D+/R−) kidney transplant recipients (KTRs). The safety and efficacy of letermovir for CMV prophylaxis in adult Japanese KTRs are reported here.MethodsIn this Phase 3, single-arm, open-label study, adult Japanese KTRs with CMV serostatuses D+/R−, D+/R+, and D−/R+ received letermovir 480 mg daily orally within 7 days post-transplant through Week 28. Participants were followed through Week 52. The primary objective was to evaluate letermovir safety and tolerability. Efficacy was a secondary objective, measured by CMV disease, CMV disease or infection requiring intervention, and quantifiable CMV DNAemia. All CMV disease cases were confirmed by an independent adjudication committee.ResultsAmong 22 participants (12 were D+/R−) who received letermovir prophylaxis, 20 (90.9%) experienced ≥ 1 AE through Week 28. Most AEs were mild to moderate in severity; no deaths were reported. During the prophylaxis period through Week 28, one transient case of quantifiable CMV DNAemia was detected, but no CMV disease or infection requiring intervention was reported. Through Week 52, four D+/R− participants met the endpoint of CMV disease or infection requiring intervention, of whom two had committee-confirmed CMV syndrome; all recovered with CMV therapy. A total of 5 participants had quantifiable CMV DNAemia through Week 52.ConclusionLetermovir was generally well tolerated, and the data support its use for the prevention of CMV disease/infection in adult Japanese KTRs.Trial registrationClinicalTrials.gov NCT04129398.

Imlifidase in kidney transplantation.

Kidney transplantation, the gold-standard therapeutic approach for patients with end-stage kidney disease, offers improvement in patient survival and quality of life. However, broad sensitization against human leukocyte antigens often resulting in a positive crossmatch against the patient's living donor or the majority of potential deceased donors in the allocation system represents a major obstacle due to a high risk for antibody-mediated rejection, delayed graft function and allograft loss. Kidney-paired donation and desensitization protocols have been established to overcome this obstacle, with limited success. Imlifidase, a novel immunoglobulin G (IgG)-degrading enzyme derived from Streptococcus pyogenes and recombinantly produced in Escherichia coli, is a promising agent for recipients with a positive crossmatch against their organ donor with high specificity towards IgG, rapid action and high efficacy in early pre-clinical and clinical studies. However, the rebound of IgG after a few days can lead to antibody-mediated rejection, making the administration of potent immunosuppressive regimens in the early post-transplant phase necessary. There is currently no comparative study evaluating the efficiency of imlifidase therapy compared with conventional desensitization protocols along with the lack of randomized control trials, indicating the clear need for future large-scale clinical studies in this field. Besides providing a practical framework for the clinical use of the agent, our aim in this article is to evaluate the underlying mechanism of action, efficiency and safety of imlifidase therapy in immunologically high-risk kidney transplant recipients.

Red blood cells as oxygen carrier during normothermic machine perfusion of kidney grafts: Friend or foe?

Renal ex vivo normothermic machine perfusion (NMP) is under development as an assessment tool for high-risk kidney grafts and as a means of achieving more physiologically accurate organ preservation. On-going hemolysis has been reported during NMP, as this technique relies on red blood cells for oxygen delivery. In this study, we confirm the occurrence of progressive hemolysis during 6-hour kidney NMP. NMP-associated erythrostasis in the glomeruli and in peri-glomerular vascular networks points to an interaction between the red blood cells and the graft. Continuous hemolysis resulted in prooxidative changes in the perfusate, which could be quenched by addition of fresh frozen plasma. In a cell-based system, this hemolysis induced redox stress and exhibited toxic effects at high concentrations. These findings highlight the need for a more refined oxygen carrier in the context of renal NMP.

Outcomes of immunological high risk kidney transplantation

Outcomes of immunological high risk kidney transplantation

Single-dose antithymocyte globulin in standard immunological risk kidney transplant recipients: efficacy and kinetics of peripheral blood CD3+ T lymphocyte modulation.

Polyclonal anti-T cell antibodies (ATG or thymoglobulin®) are used as induction therapy in kidney transplant recipients. This study evaluates the safety, efficacy, and CD3+T lymphocyte modulation of two ATG regimens. The trial included two cohorts of kidney transplant recipients that were followed for one year. The study group, including standard immunological risk recipients, received one 3mg/kg dose of ATG. The comparator group, including standard and high immunological risk kidney transplant recipients, received a fractionated dose regimen (up to four 1.5mg/kg doses). Patient and graft outcomes and the kinetics of CD3+T lymphocyte modulation in the peripheral blood were evaluated. One hundred kidney transplant recipients were included in each group. The one-year incidence of treated acute rejection, and patient and graft survival did not differ between groups. Bacterial infections were significantly more frequent in fractionated-dose group patients (66%versus 5%; P = 0.0001). At one-year follow-up, there was no difference in the incidence of cytomegalovirus infection (P = 0.152) or malignancies (P = 0.312). CD3+T lymphocyte immunomodulation in the single-dose group was more effective in the first two days after transplantation. After the third post-transplant day, CD3+T lymphocyte modulation was more efficient in the fractionated dose group. Both regimens resulted in low rejection rates and equivalent survival. The single and reduced dose regimen protects from the occurrence of bacterial infections. CD3+T lymphocyte modulation occurred with different kinetics, although it did not result in distinct outcomes.

Prediction of High-Risk Donors for Kidney Discard and Nonrecovery Using Structured Donor Characteristics and Unstructured Donor Narratives

Despite the unmet need, many deceased-donor kidneys are discarded or not recovered. Inefficient allocation and prolonged ischemia time are contributing factors, and early detection of high-risk donors may reduce organ loss. To evaluate the feasibility of machine learning (ML) and natural language processing (NLP) classification of donors with kidneys that are used vs not used for organ transplant. This retrospective cohort study used donor information (structured donor characteristics and unstructured donor narratives) from the United Network for Organ Sharing (UNOS). All donor offers to a single transplant center between January 2015 and December 2020 were used to train and validate ML models to predict donors who had at least 1 kidney transplanted (at our center or another center). The donor data from 2021 were used to test each model. Donor information was provided by UNOS to the transplant centers with potential transplant candidates. Each center evaluated the donor and decided within an allotted time whether to accept the kidney for organ transplant. Outcome metrics of the test cohort included area under the receiver operating characteristic curve (AUROC), F1 score, accuracy, precision, and recall of each ML classifier. Feature importance and Shapley additive explanation (SHAP) summaries were assessed for model explainability. The training/validation cohort included 9555 donors (median [IQR] age, 50 [36-58] years; 5571 male [58.3%]), and the test cohort included 2481 donors (median [IQR] age, 52 [40-59] years; 1496 male [60.3%]). Only 20% to 30% of potential donors had at least 1 kidney transplanted. The ML model with a single variable (Kidney Donor Profile Index) showed an AUROC of 0.69, F1 score of 0.42, and accuracy of 0.64. Multivariable ML models based on basic a priori structured donor data showed similar metrics (logistic regression: AUROC = 0.70; F1 score = 0.42; accuracy = 0.62; random forest classifier: AUROC = 0.69; F1 score = 0.42; accuracy = 0.64). The classic NLP model (bag-of-words model) showed its best metrics (AUROC = 0.60; F1 score = 0.35; accuracy = 0.59) by the logistic regression classifier. The advanced Bidirectional Encoder Representations From Transformers model showed comparable metrics (AUROC = 0.62; F1 score = 0.39; accuracy = 0.69) only after appending basic donor information. Feature importance and SHAP detected the variables (and words) that affected the models most. Results of this cohort study suggest that models using ML can be applied to predict donors with high-risk kidneys not used for organ transplant, but the models still need further elaboration. The use of unstructured data is likely to expand the possibilities; further exploration of new approaches will be necessary to develop models with better predictive metrics.

Assessment of Disparities in Access to Valganciclovir Cytomegalovirus Prophylaxis in High-Risk African American Kidney Transplant Patients

Assessment of Disparities in Access to Valganciclovir Cytomegalovirus Prophylaxis in High-Risk African American Kidney Transplant Patients

Real-World Experience With CMV inSIGHT T Cell Immunity Testing in High-Risk Kidney and Pancreas Transplant Recipients.

Cytomegalovirus (CMV)-specific cell-mediated immunity is important for control of CMV after transplant. Assays exist to measure this, but their place in therapy is unclear, particularly in CMV high-risk recipients, without pretransplant exposure. The objective of this study was to evaluate predictive potential of a positive assay to determine freedom from DNAemia and describe subsequent 3-month CMV outcomes. Adult CMV high-risk kidney and/or pancreas transplant recipients were included if a CMV inSIGHT T Cell Immunity Panel (TCIP, Eurofins Viracor) was ordered and resulted between 1 August, 2019 and 30 July, 2022. Seventy-six patients were included in our study; 49 tested during prophylaxis and 27 during treatment. Most TCIP assays obtained in the prophylaxis cohort were negative (n = 46, 93.9%). Rate of post-TCIP CMV infection was 10.2%. In those tested during treatment, 33.3% were positive and rate of post-TCIP CMV recurrence was 22.2%. The positive predictive value of the assay to successfully predict immunity was 66.7% during both prophylaxis and treatment. There were 4 cases of TCIP predictive failure with progressive CMV replication. At time of replication, 2 patients had concomitant clinical confounders thought to influence immune control of viral replication. All patients had intensification of immunosuppression prior to recurrent replication, but after TCIP was collected. The data obtained from the TCIP are not static, immune control of CMV in latency can change and must be evaluated in clinical context. Timing of TCIP after transplant is significant, and patient-specific factors remain important to assess the likelihood of CMV in each unique patient-specific scenario. A CMV stewardship program can aid in application and interpretation of results.

Profilaksis vs. Terapi Preemtif Penyakit Cytomegalovirus (CMV) pada Pasien Transplantasi Ginjal Risiko Tinggi: Suatu Laporan Kasus Berbasis Bukti

Kidney transplant recipients require the use of immunosuppressive agents to prevent multiple organ rejection. Administration of immunosuppressive agents triggers an increased risk of impaired immunity and microbial infections, one of which is cytomegalovirus (CMV). Prevention of cytomegalovirus infection can be given as a prophylaxis or preemptive therapy. However, the efficacy of choosing prophylaxis or preemptive therapy is still under debate, thus we conducted this study to identify current approach in preventing CMV disease in clinical practice. A literature search was carried out using the PubMed, Cochrane Library, Embase and Scopus databases with the keywords “high risk kidney transplant”, “prophylaxis”, “preemptive” and “CMV infection disease”. Inclusion criteria were only studies in adult kidney transplant patients as a population. , prophylaxis as intervention, preemptive therapy as comparison, and cytomegalovirus infection as outcome. The exclusion criteria of this study were the study articles that were not in Bahasa Indonesia or English, case reports and studies with subjects &lt;18 years old. Critical review using Oxford Center for Evidence Based Medicine (CEBM) Critical Appraisal Tools for Prognostic Study And Systematic Review. The total number of articles identified based on the keywords used is 115 articles. Eliminating duplication with EndNote resulted in 92 articles. Furthermore, exclusion was carried out based on title and abstract so that 29 articles were filtered for which the full text was available. Of these, 23 articles did not have appropriate research questions, 3 studies did not have appropriate patient populations, and 3 articles with types that did not meet the inclusion criteria of this study. As a result, there were 4 articles that can be used in this report. Based on those four articles, it can be concluded that prophylaxis is more effective in preventing CMV disease but had more side effects, when compared to preemptive therapy. However, there was no difference in long term outcome between kidney transplant patients with CMV prophylactic or preemptive therapy.