Transplant Patients Research Articles

Cytomegalovirus infection in transplant patients according to pre-transplant risk in a Hospital in Northeastern Mexico

Abstract Background Cytomegalovirus (CMV) is an important cause of morbidity and mortality in patients who receive a hematopoietic stem cell transplant (HSCT). It is possible to stratify the risk of developing the disease due to this agent according to the serological status of the HSCT donor and recipient. In post-transplant patients, significant T lymphocyte dysfunction occurs, so reactivation of CMV is common, which is why it should be monitored after HSCT. Our objective is to determine the association of CMV infection in post-transplant patients according to pre-transplant risk status. Methods Patients who received HSCT from January 2019 to June 2023 were included, they were classified according to their pre-transplant risk status and CMV infection was diagnosed by performing a viral load on day 30. Results 70 patients with hemato-oncological diseases who received an HSCT were included, a median age of 9 years (0-16) was found, predominance of the male sex (60%), the most frequent type of transplant was haploidentical (82.9 %). Of these, 20 (28.5%) had CMV infection, with pre-transplant risk status mostly high risk (85%), of the low-risk patients (25.7%) 10% had the infection and the very high risk (4.3%) only 5% were reported infected. The period during which the infection occurred most frequently was in the early post-pregnancy stage (66.6%) and the majority received treatment with valganciclovir (95%). Of the patients infected with CMV, 15 (75%) were asymptomatic, and 5 (25%) had associated symptoms, with 2 (10%) presenting with urinary symptoms (dysuria, frequency, suprapubic pain, tenesmus), and 2 (10%) with fever, and 1 hematochezia (5%). Regarding clinical outcomes, 17 patients (85%) presented resolution of the disease, 1 (5%) presented therapeutic failure and 1 (5%) died due to multiple organ failure. Conclusion Due to the high prevalence of CMV infection, it is important to maintain a high index of suspicion of this pathology in this population, with the aim of achieving early diagnosis and timely initiation of treatment.

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients

Abstract Background Valganciclovir (VGCV) prophylaxis against cytomegalovirus (CMV) infection and disease has provided an important advance in the management of pediatric solid organ transplantation (SOT) recipients over the past two decades. However, there remain significant questions regarding its relative safety and efficacy, optimal dosing strategies, and toxicities including neutropenia and lymphopenia. We performed a multi-center retrospective study of children post SOT who were to receive at least 3 months of valganciclovir. The primary outcomes were CMV DNAemia while receiving prophylaxis (breakthrough) and post-prophylaxis CMV DNAemia within the first year. Methods The study population included patients ≤ 20 years of age at the time of their first transplant between January 2016 and December 2019 from 8 US centers in PIDTRAN Network. Data for each patient was extracted from the electronic medical record and entered into a REDcap database hosted by St. Jude Children’s Research Hospital. Variables analyzed included demographics, donor/recipient CMV serostatus, immunosuppression, trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis use, rejection, other viral or bacterial infections and one-year survival. Statistics were performed using STATA software for univariate and multivariate models; p-value< 0.05 was considered statistically significant. Results 749 pediatric SOT patients were enrolled over the 3-year study period. Breakthrough DNAemia occurred in 85 (11.4%) patients and post-prophylaxis CMV DNAemia was documented in an additional 46 (6.9%) patients. CMV disease occurred in only 30 patients (4%). In univariate analysis, there were no differences in age, sex, race/ethnicity, or immunosuppression comparing those who experienced breakthrough or post-prophylaxis CMV DNAemia compared to those without CMV DNAemia, but there were differences based on transplanted organ (p< 0.001, liver and lung > heart > kidney) and CMV risk status (high and intermediate) (p<0.001). Neutropenia (p<0.001) and lymphopenia (p=0.003) as well as VGCV discontinuation or dose reduction for perceived toxicity (p<0.001) were associated with breakthrough CMV infection. Bacteremia (p=0.001), EBV viremia (p=0.02), and adenovirus viremia (p=0.002) were also documented more in those with breakthrough compared to those who never had CMV DNAemia. In an adjusted Cox regression hazard model using all significant univariate variables, transplanted organ, CMV risk status, toxicity related VGCV modification (p=0.005), and bacteremia (p=0.01) were independently associated with breakthrough CMV infection. Breakthrough CMV was also associated with rejection (p=0.01) in a separate logistic multivariable model. Both liver (p<0.001) and heart transplant (p<0.001) patients had a greater risk of rejection over the first year of transplantation, but only liver transplant patients had a greater risk of rejection with breakthrough CMV infection (p=0.004). Post prophylaxis CMV DNAemia was associated with mortality at 1 year in the univariate analysis in the full cohort (p=0.001). Conclusion Rates of CMV disease when using valganciclovir prophylaxis were low in this large, multicenter cohort of pediatric SOT recipients. However, breakthrough CMV infection continues to be a problem in intermediate- and high-risk CMV patients and is associated with significant morbidity and rejection, particularly in the liver transplant population. Alternative approaches to prevent breakthrough and post-prophylaxis CMV and with a better safety profile should be studied in pediatric SOT patients.

Maribavir use in pediatric immunocompromised hosts: A case series to talk about real-world experience

Abstract Background Cytomegalovirus (CMV) is a common infection affecting pediatric immunocompromised hosts. The treatment of CMV in solid organ (SOT) or hematopoietic stem cell transplant (HSCT) patients is challenged by the toxicities associated with antiviral therapies (myelosuppression with valganciclovir, ganciclovir and cidofovir; nephrotoxicity with foscarnet and cidofovir) and the prevalence of resistant/refractory CMV. Maribavir, a novel benzimidazole, competitively inhibits CMV UL97 protein kinase to inhibit DNA synthesis and block nuclear exit of viral particles from CMV-infected cells. It is FDA approved for use in patients at least 12 years of age and weighing at least 35 kg. The use of maribavir in pediatric patients is of interest due to its availability as an oral dosage formulation and improved side effect profile. To date, there are no pediatric case series or studies describing the use of maribavir for CMV treatment. Methods This study is a retrospective case series compiling the findings the first pediatric patients at Children’s National Hospital, DC that received maribavir. We included children who received maribavir from 01/2017 – 10/2023. Patients were included if they were on maribavir monotherapy, or combination therapy with additional anti-CMV agent(s). The medical records were reviewed for indication of medication use, viral response to therapy and side effects. Side-effects review specifically evaluated for increased LFTs, increased serum creatinine, and decreased absolute neutrophil count or factors that may contribute to early discontinuation of maribavir. Results (table) Maribavir was used in three male patients with varied conditions – including solid organ transplant (SOT), hematopoietic stem cell transplant (HSCT) and Severe Combined Immunodeficiency (SCID) s/p HSCT. Two cases had signs of CMV disease, and one had CMV viremia. All cases included documented CMV resistance (n=2) or refractory CMV (n=1) and had previously been receiving at least one antiviral with CMV activity for at least 14 days and had increasing CMV DNA-emia in the blood. None of the patients had side effects such as nephrotoxicity, liver toxicity or myelosuppression that aggravated after starting maribavir. Dosing of 400mg BID (range 12mg/kg/day to 55mg/kg/day) was used. Once started, maribavir was continued until CMV quantitative levels were undetectable for two weeks. Clearance of CMV and was achieved in all the patients on maribavir or combination of maribavir with other drugs (n=1). Duration of maribavir treatment ranged from 4.2 to 6.2 weeks. Conclusion This is the first case series describing use of maribavir in a pediatric population. In this small cohort maribavir is effective and well tolerated. Further studies are needed to better CMV care in children with immunocompromised conditions.

Use of T2Bacteria Panel in Pediatric Hematopoietic Stem Cell Transplant Patients: A Single Center Experience

Abstract Background Bloodstream infection is a common complication following hematopoietic cell transplant (HCT), occurring in 10-40% of patients (1,2). Rapid identification of causative bacteria is imperative to provide proper empiric therapy and ensure optimal patient outcomes. The T2Bacteria Panel detects five bacterial pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli) using T2 magnetic resonance (T2MR, T2Biosystems, Lexington MA, USA) directly from blood specimens. Previous studies have reported per-patient sensitivity, specificity, and negative predictive value (NPV) of 84-90%, 85.9-90%, and 99.7%, respectively, as well as 100% positive agreement and 98.4% negative agreement when compared to blood culture (3-5). To date, there have been no studies on the use of this test in pediatric HCT recipients. Methods We reviewed all pediatric HCT patients at St. Jude Children’s Research Hospital who had a T2Bacteria Panel performed for fever and suspected infection between January 2019 and September 2022. A total of 706 T2Bacteria Panel results and concurrent blood culture results from 251 unique patients were analyzed to determine assay performance for detection of the 5 targeted pathogens. Results T2Bacteria PCR and blood culture showed concordant results in 97% of cases. Overall, our study revealed 65% positive percent agreement with blood culture and 95% negative percent agreement for bacteremia caused by any of the target pathogens. PPV, NPV, sensitivity and specificity for each organism detected by the panel, and the panel overall, are presented in Table 1. Positive predictive value ranged from 28-73%. Negative predictive value was high for all organisms (98-100%). Sensitivity was highest for Pseudomonas aeruginosa (88%), and lowest for Escherichia coli (44%). Specificity was high for all organisms (97-99%). Conclusion In pediatric HSCT patients, the T2Bacteria Panel was most useful for rapidly ruling out the presence of target pathogens, with high negative percent agreement, NPV, and specificity. Positive percent agreement was lower than noted in previous studies. Positive predictive value and sensitivity varied per pathogen.

Study of related factors to vascular complications after pediatric liver transplantation

Objective: To explore the related factors of vascular complications after liver transplantation in children. Methods: This is a retrospective case-series research. The clinical data of 89 pediatric liver transplant patients admitted to the Organ Transplantation Center, the Affiliated Hospital of Qingdao University from January 2016 to March 2024 were collected retrospectively. This study included 44 males and 45 females,aged from 4 months to 17 years. The ratio of graft to recipient weight was 0.6% to 7.7%. The primary diseases included 48 cases of biliary atresia and 41 cases of non-biliary atresia. The t-test, Wilcoxon rank sum test, χ2 test, and Fisher's exact probability method were used for data analysis. Multivariate Logistic regression was used to analyze the related factors of vascular complications. Results: All 89 children with liver transplantation completed surgery successfully. There were 8 cases of arterial complications after surgery, including 6 cases of hepatic artery thrombosis and 2 cases of hepatic artery stenosis. There were 16 cases of portal vein complications after surgery, including 9 cases of portal vein stenosis and 7 cases of portal vein thrombosis. The results of univariate analysis showed that the age of the recipient ≤1 year was the relevant factor for hepatic arterial complications(χ2=4.772,P=0.029). The age of the recipient ≤1 year, the age of the donor, the hepatic phase, and the time of cold ischemia were the relevant factors for the occurrence of portal vein complications(χ2=7.270,Z=388.500,Z=838.000, Z=594.500;all P<0.05). The results of multivariate analysis showed that age(≤1 year vs. >1 year) and duration of cold ischemia(every additional 1 hour) were independent related factors for portal vein complications after liver transplantation in children(both P<0.05). Conclusion: Children aged ≤1 year and with prolonged cold ischemia are more likely to develop portal vein complications after liver transplantation.

Veno-arterial extracorporeal membrane oxygenation as bridge for fluid resuscitation in a patient with acute respiratory failure and circulatory shock two years post lung transplantation.

The use of extracorporeal membrane oxygenation (ECMO) continues to evolve and is recognized as an important adjunct as a bridge to recovery or a bridge to transplant. We wanted to share our experience of using veno-arterial (VA) ECMO as an adjunct to lung recovery and an aide for fluid resuscitation. We present the case of a 77-year-old man with a history of previous single lung transplant who had acute respiratory decompensation and cardiovascular collapse secondary to CMV pneumonia and septic shock. He was cannulated for VA ECMO, treated for CMV pneumonia and resuscitated with 5L of albumin 5% and antibiotics, within 12 hours of cannulation. He required twodays of VA ECMO and was ultimately decannulated and discharged to a rehabilitation facility on hospital day 73. This case emphasizes the challenging clinical scenario of fluid resuscitation in a lung transplant patient. With adequate patient selection, a multidisciplinary team and the use of VA ECMO, success can be achieved.

Risk Factors of Cytomegalovirus Retinitis Occurrence After Allogeneic Hematopoietic Stem Cell Transplantation

ABSTRACT Purpose To explore the potential risk factors for the occurrence of human cytomegalovirus (HCMV) retinitis (CMVR) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. Methods This is a retrospective, nested case-control study conducted in hematological patients with CMVR who underwent allo-HSCT. Patients diagnosed with CMVR after allo-HSCT were included as the case group, and those without CMVR were matched by a ratio of 1:2 and were recruited as controls. We selected 19 pre- and post-transplant indicators for univariate analysis between the cases and controls, and then Logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) for exploration of risk factors of the CMVR occurrence. Results A total of 1308 allo-HSCT patients from January 1, 2020 to July 31, 2023 were analyzed, and 27 patients were diagnosed CMVR with a median onset time of 222 days after transplantation. In univariate analysis, donors of stem cells source, HLA-match types (including matched sibling donor, haploidentical donor, and unrelated donor), post-transplant Epstein-Barr virus (EBV) viremia, platelet implantation time, and serostatus of CMV-IgG were more easily to develop CMVR than controls (p < 0.001, p = 0.003, p < 0.001, p = 0.032, p = 0.038, respectively). Multivariate logistic regression analysis showed that stem cells source (OR 7.823, 95% CI 1.759-34.800), HLA-match types (OR 7.452, 95% CI 1.099-50.542), and post-transplant EBV infection (OR 7.510, 95% CI 1.903-29.640) were positively associated with the onset of CMVR. Conclusion Stem cells derived from bone marrow and peripheral blood, HLA-match types, and post-transplant EBV viremia are important risk predictors of CMVR in allo-HSCT patients. These results suggest that clinicians should pay more attention to these indicators when formulating preventive measures pre- and post-transplant.

Current Practices and Recent Advances in Perioperative Pain Management for Liver Transplantation Living Donors and Recipients.

Analgesia in liver transplantation patients has been traditionally considered a secondary priority where perioperative management principally focused on survival rates in these critically ill patients. With recent advancements in both surgical and medical management, posttransplant survival rates have steadily improved. Outcome measurements are no longer limited to short-term mortality rates and hospital length of stay but are also measured by patient-centered outcomes, such as pain control and quality of life. As living donor liver transplantation has increased access to transplantation, it has also added a different patient population to manage in the perioperative period. For healthy patients undergoing living donor hepatectomies, it is important to reduce the impact of the surgery with proper perioperative pain management. We performed a literature search for articles related to perioperative pain management for liver transplantation living donors and recipients to identify current practices and recent advances. Neuraxial techniques, peripheral nerve blocks, and enteral and parenteral medications were all found to be feasible analgesia modalities for patients undergoing either liver transplant or donor hepatectomy. Patients may also benefit from nonpharmacological interventions and preoperative counseling. No particular perioperative analgesic modality was deemed superior to any other. For liver transplant living donors and recipients, perioperative pain management should emphasize the application of sustainable patient-centered pain control protocols.

Drug-drug interactions between letermovir and tacrolimus in Japanese renal transplant recipients simulated using a physiologically based pharmacokinetic model.

Letermovir (LET) is a novel antiviral agent recently approved for cytomegalovirus (CMV) prophylaxis of renal transplant patients in Japan. However, its interactions with tacrolimus (TAC), an important immunosuppressant, remain ambiguous, warranting careful evaluation considering the unique genetic and physiological characteristics of Japanese patients. Therefore, in this study, we aimed to investigate the drug-drug interactions between LET and extended-release TAC (ER-TAC) in Japanese renal transplant patients via physiologically based pharmacokinetic (PBPK) modeling. We developed PBPK models for LET and TAC, including a new model for ER-TAC, using the Simcyp simulator. We also created a virtual Japanese post-transplant population by incorporating physiological parameters specific to Japanese patients, including CYP3A5 genotypes. Our model accurately predicted the pharmacokinetics of both immediate-release and ER-TAC co-administered with LET. In the Japanese population, LET significantly increased ER-TAC exposure, with the effect varying by CYP3A5 genotype. For CYP3A5*1 carrier, the area under the curve ratio ranged from 2.33 to 2.53, while for CYP3A5*3/*3 carriers, it ranged from 2.82 to 2.86. The maximum concentration ratio was approximately 1.50 across all groups. Our findings suggest reducing the ER-TAC dose by approximately 57-60% for CYP3A5*1 carrier and 65% for CYP3A5*3/*3 carriers when co-administered with LET for Japanese renal transplant patients. Moreover, the developed model incorporating population-specific factors, such as hematocrit values and CYP3A5 genotype frequencies, is a valuable tool to evaluate complex drug interactions and guide the dosing strategies for LET and TAC in Japanese patients. Overall, this study expands the application of PBPK modeling in transplant pharmacology, contributing to the development of effective immunosuppressive strategies for Japanese renal transplant patients.

Summary of Best Evidence for Perioperative Management Practices in Hair Transplantation Patients : Facial Skeleton.

To integrate and summarize the best evidence on perioperative management practices for hair transplantation patients, providing an evidence-based reference for clinical. An exhaustive literature search was conducted to identify the best evidence for managing patients undergoing hair transplantation during the perioperative period. The databases searched included Up To Date, BMJ Best Practice, UK National Institute for Health and Care Excellence, National Guideline Clearing House, Scottish Intercollegiate Guidelines Network, Guidelines International Network, Cochrane Library, JBI Database of Systematic Reviews and Implementation Reports, PubMed, Web of Science, European Dermatology Forum, China National Knowledge Infrastructure, Wanfang Data, Medlive Guideline Network, and Sinomed. The search spanned publications from February 2013 to February 2024, focusing on clinical decisions, evidence summaries, guidelines, and expert consensus. We finally identified 22 articles with high-quality results (consisting of 9 clinical decisions, 6 guidelines, 7 expert consensuses), providing 41 pieces of evidence across seven categories: assessment of transplantation conditions, transplant planning and preoperative preparation, anesthetic preparations, surgical methods and operation skills, postoperative wound management, medication-related guidance, optimization of nursing and treatment strategies. Special emphasis has been placed on the sections covering anesthesia preparation, surgical methods, and operational techniques, with detailed explanations provided. The summarized best evidence on perioperative management practices for hair transplantation patients can serve as evidence-based guidelines for clinical. It is recommended that clinical staff adopt evidence-based recommendations to improve and optimize patient outcomes and promote postoperative recovery. As these evidences came from different countries, factors such as the clinical environment should be evaluated before application. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Associations between Kidney Disease Progression and Metabolomic Profiling in Stable Kidney Transplant Recipients-A 3 Year Follow-Up Prospective Study.

Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results: The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m2 vs. 55.8 mL/min/1.73 m2, p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found (F (1,70) = 5.15, p = 0.026), with an R2 of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = -0.250 and p = 0.04, citric acid with r = -0.296 and p = 0.014, formic acid with r = -0.349 and p = 0.004, and glycine with r = -0.306 and p = 0.01). Conclusions: some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites.

Management of blood lipids in post-kidney transplant patients: a systematic review and network meta-analysis.

The primary objective of this systematic review was to provide an overview of the efficacy and safety of various lipid-lowering therapies in patients post-kidney transplant (PKT), given the limited existing literature. Considering the restricted number of available studies, this work aimed to summarize the existing evidence regarding the effectiveness of different lipid-lowering treatments in PKT patients. The effects of various lipid-lowering therapeutic regimens on lipid levels were compared, and their safety was assessed, with the heterogeneity of treatment protocols acknowledged. Randomized controlled trials investigating different treatment regimens (DTRs) for regulating lipid levels in PKT patients were systematically retrieved from PubMed, Cochrane Library, and Embase, from inception to March 2024. Literature quality was assessed employing the Cochrane risk of bias assessment tool. Data analysis and graphical representation were performed employing RevMan5.3 and Stata 20.0. The surface under the cumulative ranking area (SUCRA) compared the effects of DTRs on lipid profiles, incidence of adverse events, and all-cause mortality in PKT patients. Fifteen studies were included, comprising 5,768PKT patients and involving 9 treatment regimens. The results revealed that, for changes in high-density lipoprotein cholesterol (HDL-C), the SUCRA rankings from highest to lowest among PKT patients receiving DTRs were statins + ezetimibe (70%), placebo (61.5%), fibrates (57.2%), statins (44.1%), and fish oil (17.3%). Regarding changes in low-DL-C (LDL-C), the SUCRA rankings from highest to lowest among PKT patients receiving DTRs were statins (68.2%), statins + ezetimibe (67.5%), fish oil (53.4%), fibrates (34.5%), and placebo (26.5%). For the change in total cholesterol (TC) levels, a network meta-analysis (NMA) revealed that among PKT patients receiving DTRs, the SUCRA rankings from highest to lowest for TC change were statins + ezetimibe (97.6%), proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors) (74.3%), fish oil (64.3%), statins (61.6%), fibrates (47.2%), placebo (31.6%), calcineurin phosphatase inhibitors (11.9%), and immunosuppressants (11.4%). Regarding the change in triglyceride (TG) levels, a NMA showed that among PKT patients receiving DTRs, the SUCRA rankings from highest to lowest for TG change were fibrates (99.9%), statins (68.9%), PCSK9 inhibitors (66.6%), statins + ezetimibe (55.1%), placebo (49.2%), fish oil (45.0%), immunosuppressants (7.8%), and calcineurin phosphatase inhibitors (7.6%). For the occurrence of kidney transplant failure, a NMA revealed that among PKT patients receiving DTRs, the SUCRA rankings from highest to lowest for reducing the incidence of kidney transplant failure were PCSK9 inhibitors (69.0%), calcineurin phosphatase inhibitors (63.0%), statins (61.5%), placebo (55.1%), steroids (51.8%), immunosuppressants (27.1%), and fibrates (22.5%). Regarding all-cause mortality, a NMA showed that among PKT patients receiving DTRs, the SUCRA rankings from highest to lowest for reducing all-cause mortality were PCSK9 inhibitors (90.5%), statins (55.8%), and placebo (3.7%). In reducing lipid levels in PKT patients, combination therapy with statins and ezetimibe demonstrated notable advantages and higher effectiveness. PCSK9 inhibitors exhibited greater advantages in reducing adverse events and mortality rates in PKT patients, with higher safety.

Frequency of human leukocyte antigen compatibility and graft rejection in kidney transplant patients from living donors

Frequency of human leukocyte antigen compatibility and graft rejection in kidney transplant patients from living donors

Immunosuppressive medication adherence and affecting factors in solid organ transplantation patients: a mixed-methods study

Objectives: Transplantation is a form of treatment that requires long-term pharmacotherapy. After transplantation, patients may have difficulty adapting to medication use for various reasons, and this may result in rejection. The aim of this study is to determine participants’ medication compliance and the factors affecting it. Methods: The research was conducted with a sequential explanatory mixed method. In the study, quantitative data were collected using the Turkish Immunosuppressive Medication Adherence Scale, and qualitative data were collected using the In-Depth Individual Interview Guide. Quantitative data were analyzed using statistical methods, and qualitative data were examined according to Braun and Clarke's thematic analysis framework. Results: In this study, 62.3% of the participants were male, 37.0% were 50 years old and over, 71.3% lived with their spouse, 54.0% had primary and secondary school education, and 42.0% could not work due to their current health condition. From a clinical perspective, it was determined that 78% of the transplants were kidney transplants, and 41.3% were more than 4 years after transplantation. 74.3% of the transplants were from living donors. The mean score of the immunosuppressive medication compliance scale was determined to be 40.91±4.09. In the qualitative data analysis of the study, factors affecting medication adherence were examined and the themes of "individual factors", "complexity of the regimen" and "social support resources" were obtained. The sub-themes of the individual factors theme are reluctance, hopelessness and addiction; Sub-themes of the complexity of the regimen theme are drug side effects and polypharmacy; The sub-themes of the social support resources theme are loneliness and family pressure. Conclusions: The factors influencing medication adherence among organ transplant recipients have been investigated, revealing that adherence levels vary significantly depending on various factors. These findings underscore the importance of tailored care strategies and individualized support approaches.

9391 Clinical Accuracy Of Continuous Glucose Monitoring In Post-kidney Transplant Patients With Type 2 Diabetes

Abstract Disclosure: Q. Aziz: None. K. Batra: None. S. Fatima: None. J. Splinter: None. A.L. Champion: None. A.M. Kumar: None. K.E. Izuora: Research Investigator; Self; Novo Nordisk. Background: Continuous glucose monitoring (CGM) devices provide real time blood glucose data to guide therapy in patients with diabetes mellitus. Diabetic nephropathy is a major complication of diabetes which can eventually lead to End Stage Renal Disease (ESRD). Kidney transplant is a treatment option for ESRD and patients who undergo kidney transplant are exposed to anti-rejection therapy, including high-dose steroids, resulting in significant fluctuations in blood glucose. Having a reliable system for monitoring blood glucose continuously, such as a CGM, can provide valuable information to guide optimal diabetes management. Objective This study aims to compare the clinical accuracy of the CGM data with the Point of Care Testing (POCT) glucose values as a reference among post kidney transplant patients with Type 2 diabetes mellitus (T2DM). Methodology This study was conducted at an academic medical center from September 2023 to January 2024, enrolling subjects ≥ 18 years, diagnosed with T2DM , admitted for kidney transplant. Following informed consent, a blinded CGM (Freestyle Libre Pro®) was applied. We collected all POCT and serum glucose values and downloaded corresponding CGM glucose data. Using matched pairs between CGM and POCT glucose values, bias and absolute relative differences (ARD) were calculated. Based on the ARD, the Clarke error grid (CEG) analysis was conducted to quantify the clinical accuracy of CGM and POCT by assigning glucose data points into 5 zones A, B, C, D, and E. Summary statistics for numeric variables included mean and standard deviation, whereas categorical variables were described as counts and proportions. All analyses were performed using SAS, 9.4 version. Results: A total of 22 subjects were analyzed after excluding one patient due to CGM malfunction. Subjects were 58±9.69 years old, and 82% were males. The mean body mass index was 30±6.41 kg/m2 and mean HbA1c was 6.7 ± 1.07%, at baseline. The mean duration of diabetes and ESRD were 19±10.6 years and 3±2.27 years respectively. Average CGM wear time was 76±24.5 hours. The CEG comparing CGM values with POCT values showed 83.79% values in zone A, 15.29% in zone B (combined =99.08%) with the Mean Absolute Relative Difference (MARD) of 13.24%. The CEG comparing CGM values with serum glucose showed 83.1% values in zone A, 16.9% in zone B (combined =100%) with the MARD of 13.10%. Conclusion: Our results indicate that CGM values are comparable to the POCT and serum glucose values in post kidney transplant patients with T2DM receiving high dose steroids. Therefore, use of CGMs should be considered as a useful tool, providing timely information to guide prompt interventions and improve outcomes in this patient population. Presentation: 6/3/2024

6984 New Onset Diabetes After Transplant: Need for Strict Glucose Monitoring

Abstract Disclosure: T. Chaudhary: None. O. Syed: None. M. Nawaz: None. R. Kaur: None. Introduction: Immunosuppressant use comes at a cost of challenging side effects, which are being discovered more as its use increases. One such example is our case of new-onset diabetes after transplant (NODAT).Patient presentation: A 36-year-old male with a past medical history of end-stage renal disease status post renal transplant (6/2023), hypertension, and hyperlipidemia who presented to the hospital in 10/2023 with fever, chills, and diarrhea. His vitals at that time were as follows: temperature 36.1C, blood pressure 148/84 mmHg, pulse 87 bpm, and a respiratory rate of 22. Lab work was significant for blood glucose 1144, anion gap 22, bicarbonate 13, potassium 7.3, Sodium 135, lipase 427, pH 7.3, urine ketones 80, HbA1C 11.5 %. CT scan of the abdomen revealed loss of peripancreatic fat and inflammatory changes surrounding the pancreas. His medication review included Tacrolimus 12 mg daily, Mycophenolate 500 mg BID, Valtrex 500mg daily, and fluconazole 200mg every other day. He was treated with 2 liters of normal saline bolus and started on maintenance fluid, and insulin drip as per DKA protocol. Calcium gluconate and an albuterol nebulizer were given for hyperkalemia. Tacrolimus and prednisone were held. Endocrinology and Nephrology were consulted. The patient was thought to have diabetes due to steroid use which were discontinued and the patient was discharged on subcutaneous insulin regimen and lower dose of tacrolimus. Despite discontinuation of steroids, patients continued to have raised glucose readings confirming the causative agent as tacrolimus. Conclusion: The current guidelines for post-kidney transplant patients recommend checking fasting blood glucose weekly for the first four weeks, then biweekly for two months, and then monthly thereafter. HbA1C should be checked every 3 months and if it is &amp;gt;6% then home glucose monitoring should be done as well. Although the frequency of these check-ups decreases, it is imperative for physicians to remember that patients can still develop NODAT months post-transplant. It is also essential to reinforce the importance of these glucose checks for the patient as missed diagnosis can lead to dangerous complications such as DKA. Presentation: 6/2/2024

Association between Respiratory Virus Infection and Development of De Novo Donor-Specific Antibody in Lung Transplant Recipients.

Chronic lung allograft dysfunction (CLAD) is the most common cause of long-term lung allograft failure. Several factors, including respiratory virus infection (RVI), have been associated with CLAD development, but the underlying mechanisms of these associations are not well understood. We hypothesize that RVI in lung transplant recipients elicits the development of donor-specific antibodies (DSAs), thus providing a mechanistic link between RVI and CLAD development. To test this hypothesis, we retrospectively evaluated for the presence of HLA antibodies in a cohort of lung transplant recipients with symptomatic RVI within the first four months post-transplant using sera at two time points (at/directly after the transplant and following RVI) and time-matched controls without RVI (post-transplant). We found a trend toward the development of de novo DSAs in those with symptomatic RVI versus controls [6/21 (29%) vs. 1/21 (5%), respectively, p = 0.09]. No cases or controls had DSA at baseline. We also found increased rates of CLAD and death among those who developed class II DSA versus those who did not (CLAD: 5/7 (71.4%) vs. 19/34 (54.3%), death: 5/7 (71.4%) vs. 17/35 (48.6%)). Prospective studies evaluating the temporal development of DSA after RVI in lung transplant patients and the subsequent outcomes are warranted.

Tumor characteristics in immunosuppressed and renal dysfunction populations

PurposeRenal transplantation and end-stage renal disease are increasingly common. Renal dysfunction and immunosuppression are two risk factors in the development of renal cell carcinoma. Carcinomas in these patients are thought to be more indolent, however data are limited and mixed. Our objective was to describe the histology of resected tumors from the transplant and renal dysfunction population and compare them to a control population. Materials and MethodsThis was a single-center retrospective cohort study of all patients who had a nephrectomy for a renal mass from 2009 to 2019. All transplant status and end-stage renal disease diagnoses were identified by diagnostic or procedural coding and confirmed by chart review. Our primary endpoint was the pathology for each patient's tumor. Tumors were classified into aggressive or nonaggressive categories based on their histology and grade. ResultsWe identified 1,150 radical and partial nephrectomies, of which 1,057 met inclusion criteria. Of these, 68 patients (6.4%) had renal dysfunction or a kidney transplant on immunosuppression at time of nephrectomy. After pathologic review, 270 (25%) tumors were classified as aggressive, and 673 (64%) tumors were pT1a or pT1b. On multivariable logistic regression controlling for age and gender, renal dysfunction was not associated with having an aggressive tumor (OR 1.24, 95%CI 0.72–2.15; P = 0.44). ConclusionsWe did not observe a relationship between renal dysfunction status and aggressive pathology. These data suggest that renal dysfunction and transplant patients are at similar risk for aggressive pathology as the general population and should be managed according to the same clinical guidelines.

B-222 Receptor-donor CYP3A5 and CYP3A4 genotype testing in liver transplant patients and its influence in tacrolimus blood levels: a retrospective study

Abstract Background Optimal immunosupression is crucial for transplant success. In orthohepatic transplants, blood target levels of tacrolimus, when coadministred with corticoids and mycophenolic acid, are between 6 and 10 ng/mL during the first three months post-transplant. Notwithstanding, achieving tacrolimus concentrations into this range may be tough because of factors such as liver function status, age, sex, drug-drug interactions, etc. In this way, pharmacogenetic testing of CYP3A5 and CYP3A4 genes have demonstrated to be useful in tacrolimus dosing optimization. Nonetheless, there is no evidence enough for pharmacogenetic based adjusting in liver transplant, specially if receptor and graft’s genotypes differ in these loci. The aim of the present study is to find out how the receptor and donor genotypes in CYP3A5 and CYP3A4 genes affect tacrolimus pharmacokinetics. Methods Genotypic profiling of 108 receptor-donor's pairs biopsies gathered from patients who were underwent hepatic transplant from 2012 to 2019 were carried out using Taqman® OpenArray™ PGx Express 120 panel (ThermoFisher™). We focused on CYP3A5*3, *6 and *7; and CYP3A4*1B, *3 and *22 alleles. Next to pharmacogenetic testing, each patient was classified as very poor, poor, intermediate, rapid or ultrarapid metabolizer according to their own genotype, graft’s genotype or both of them. Patient’s initial dose, at seven days after treatment start and after discharge of tacrolimus and their trough concentrations (C0) were collected from their electronic health records. Tacrolimus levels were measured by affinity chrome-mediated immunoassay. C0 was normalized by weight-adjusted dosage (C/D ratio); then, median C/D ratios between different metabolic profiles were compared through Kruskal-Wallis test. Results When patients were classified based on donor’s genotype isolated or combined with receptor’s genotype, lower C/D ratios were found as metabolizer ability increases (p=0.045 for donors and p=0.027 for combined genotypes, respectively). No statistically differences were found for C/D ratios at seven days and discharge, though that differences were almost significant for donor’s genotypes (p=0.06 in both cases). Conclusions These results show that previous information about both patient’s and specially donor’s CYP genes genotype may improve initial immunosupression and avoid tacrolimus induced toxicity. Pharmacogenetics has been currently proposed as a guide for tacrolimus treatment of some solid organ transplants as kidney transplanted patients. Better understanding of how receptor and donor’s CYP genotype affects its pharmacokinetics, along with liver’s damage markers and other genetic polymorphisms will allow clinicians, in the era of personalized medicine, to improve immunosupressive management.

Expanding horizons: lung transplantation for non-IPF interstitial lung diseases

ObjectiveInterstitial lung diseases (ILDs) are diverse pulmonary disorders marked by diffuse lung inflammation and fibrosis. The variability in characteristics and treatment approaches complicates diagnosis and management. In advanced cases requiring transplantation, determining indications and selecting suitable candidates presents additional challenges.MethodsOf all patients with non-IPF ILD between December 2016 to December 2022 were analyzed retrospectively. Patients were categorized into two groups: transplanted patients and deceased patients on the waiting list. Clinical data and survival outcomes were compared between groups.ResultsOf the 43 patients, 20 underwent lung transplantation while 23 died awaiting transplantation. Waiting list mortality was 53.4%, with median waiting times similar between groups (3 months for transplant patients and 6 months for those on the waiting list). There were no significant differences between groups in age, gender, height, BMI, 6-minute walk test (6MWT), or forced vital capacity (FVC). The prevalence of pulmonary hypertension (PH) was 76.7% in right heart catheterizations, similar in both groups. One single and 19 bilateral lung transplants were performed. Overall, 13 of the 20 patients survived to discharge from the hospital. One-year mortality was 7/20 (35%). The median follow-up was 34 months, with a 1-year conditional survival of 90.9% at 3 years and 70.7% at 5 years.ConclusionsThis study underscores the importance of further research into non-IPF ILDs. Lung transplantation remains a viable option that can significantly enhance both the quality and longevity of life for patients with advanced ILD.