Renal Transplant Patients Research Articles

V-210.6: Observational study of factors affecting Tacrolimus trough level in renal transplant patients.

V-210.6: Observational study of factors affecting Tacrolimus trough level in renal transplant patients.

P.039: A Nation wide survey analysis on current state of immunosuppression in renal transplant patients

P.039: A Nation wide survey analysis on current state of immunosuppression in renal transplant patients

P.330: Rapid reduction of mycophenolate mofetil and calcineurin inhibitor dose for treating BK polyomavirus virus infection in renal transplant patients.

P.330: Rapid reduction of mycophenolate mofetil and calcineurin inhibitor dose for treating BK polyomavirus virus infection in renal transplant patients.

320.6: Effect of target-controlled infusion versus general inhalational anesthesia on hemodynamic parameters and post-operative outcomes among renal transplant patients: a single-center, open-label, randomized controlled trial.

320.6: Effect of target-controlled infusion versus general inhalational anesthesia on hemodynamic parameters and post-operative outcomes among renal transplant patients: a single-center, open-label, randomized controlled trial.

265.5: T regulatory cell phenotypes in renal transplant patients with long surviving graft, increased Th2-like Treg and reduced Th1- and Th17-like Treg.

265.5: T regulatory cell phenotypes in renal transplant patients with long surviving graft, increased Th2-like Treg and reduced Th1- and Th17-like Treg.

P.277: The relationship between rebound thymic hyperplasia and the risk of rejection in renal transplantation patients.

P.277: The relationship between rebound thymic hyperplasia and the risk of rejection in renal transplantation patients.

The effect of itching on sleep quality and comfort in patients with hemodialysis and renal transplantation: A multi-center cross-sectional study

BackgroundThe aim of this study was to determine the effect of itching on sleep quality and comfort in hemodialysis (HD) and renal transplant (Tx) patients with itching. MethodsThis descriptive, correlational seeking and cross-sectional study was conducted in four hospitals affiliated with a private health group in Istanbul between April and June 2021. The sample of the study consisted of 42 patients receiving HD treatment and 49 patients with renal transplantation. Data were collected using the Patient Information Form, 5-D Itch Scale, Richards-Campbell Sleep Questionnaire and General Comfort Questionnaire. ResultsThere was a significant difference between the HD and renal transplantation groups in the Direction (p = 0.01) and Disability dimension (p = 0.002) of the 5- D Itch scale in favor of the renal transplant group. The mean sleep quality and comfort scores of the groups were similar and moderate. Itching negatively affects sleep quality in patients receiving HD treatment, and 22 % of the change in sleep quality is explained by disability of itching (R2 = 0.22; p = 0.002). Itching negatively affects comfort in both groups. Itching explains 27 % of the change in comfort level in the HD group (R2 = 0.27; p = 0.002) and 25 % of the change in comfort level in the renal transplantation group (R2 = 0.25; p = 0.001). ConclusionsAccording the study results during the hemodialysis treatment process, itching is more intense in terms of distribution and disability and affects the quality of sleep of patients. Itching has a significant impact on patients' perception of comfort. Patients experience itching both during HD treatment and after renal transplantation, which significantly impairs their comfort. Therefore, itching should be carefully monitored during renal replacement therapy and its effects on patients should be evaluated.

P.075: Challenges in tacrolimus dosing in mutant CYP3A5*3/3* renal transplant patients leading to over immunosuppression and persistent post-transplant covid viremia.

P.075: Challenges in tacrolimus dosing in mutant CYP3A5*3/3* renal transplant patients leading to over immunosuppression and persistent post-transplant covid viremia.

221.5: Advancing renal transplant patient care: Unveiling eplet mismatch thresholds for precise risk assessment and prognosis.

221.5: Advancing renal transplant patient care: Unveiling eplet mismatch thresholds for precise risk assessment and prognosis.

Distribution of CYP3A4 and CYP3A5 Polymorphisms and Genotype Combination Implicated in Tacrolimus Metabolism.

Human cytochrome P450 (CYP), particularly CYP3A4 and CYP3A5 is mainly responsible for the metabolism of several drugs including tacrolimus. Significant interracial/interethnic variation in the expression and function of CYP3A5 and CYP3A4 is caused by Single Nucleotide Polymorphisms (SNPs) of genes encoding these proteins. The present study investigated the genetic polymorphisms CYP3A4*1B, CYP3A4*22, and CYP3A5*3 in the Tunisian population. We included in this study, Tunisian healthy subjects and renal transplant recipients receiving tacrolimus. CYP3A4 and CYP3A5 genotyping were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to the genotypic combination of the three CYP polymorphisms, we have identified for the first time four metabolizers statuses: slow metabolizers (SM), intermediate metabolizers (IM), high metabolizers (HM), and extensive metabolizers (EM). A total of 101 renal transplant patients and 102 healthy subjects were included. Our results showed that the predominant alleles in the Tunisian population are a wild type of CYP3A4*1B (0.87), likewise CYP3A4*22 (0.975) and CYP3A5*3 (0.82). The genotype frequencies of CYP3A4*1B, CYP3A4*22, and CYP3A5*3 were found to be 3.9%, 0.0%, and 69.5%, respectively. Also, we found a significant linkage disequilibrium between CYP3A4*1B and CYP3A5*3. We approved that the IM is the predominant phenotype in our population with 124 patients followed by and EM with 41 patients, HM in 29 patients and SM in 9 patients. These results showed that Tunisians are most similar to Caucasians. The genetic background of these enzymes CYP3A4*1B, CYP3A4*22, and CYP3A5*3 in this study are important in the prescription of personalized medicine.

Complications associated with kidney transplantation, causes of graft failure and mortality following kidney transplantation in patients with systemic lupus erythematosus: a meta-analysis

IntroductionDespite improvement in the management of systemic lupus erythematosus (SLE) during the past two decades, 10–22% of patients with lupus nephritis (LN) will progress to end-stage renal disease (ESRD). Kidney transplantation is among the possible treatment for patients with SLE progressing to ESRD. However, the issue with kidney transplantation in patients with SLE is controversial. In this analysis, we aimed to compare the complications associated with kidney transplantation, causes of graft failure and causes of mortality following kidney transplantation in patients with SLE with ESRD.MethodsThe sources of data included http://www.ClinicalTrials.gov, EMBASE, MEDLINE, Google Scholar, Web of Science and the Cochrane database. Revman software version 5.4 was used for the data analysis whereby risk ratio (RR) with 95% confidence intervals (CI) were used to represent data following analysis. In addition, the Q statistic test and the I2 statistic test were used to assess heterogeneity. A random effect statistical model was used and a subgroup outcome with a P-value less than 0.05 was considered statistically significant.ResultsA total number of 149,330 participants enrolled between the years 1968 and 2018 were included in this analysis with 7534 participants with SLE.Results of this analysis showed that mortality (RR 1.07, 95% CI 0.89–1.29; P = 0.45), graft failure (RR 1.22, 95% CI 0.99–1.55; P = 0.07) and delayed graft function (RR 1.01, 95% CI 0.44–2.34; P = 0.98) were not significantly higher in renal transplant patients with SLE versus a control group. When the causes of graft failure were analysed in renal transplant patients with SLE versus without SLE, acute graft rejection (RR 1.20, 95% CI 0.98–1.47; P = 0.07), chronic graft rejection (RR 0.76, 95% CI 0.57–1.03; P = 0.08), graft thrombosis (RR 1.47, 95% CI 0.83–2.63; P = 0.19), recurrence of disease (RR 3.08, 95% CI 1.00–9.47; P = 0.05) and chronic allograft nephropathy (RR 1.08, 95% CI 0.60–1.95; P = 0.80) were also not significantly higher in patients with SLE. On the basis of the analysis, mortality from any cardiac cause (RR 0.82, 95% CI 0.67–1.01; P = 0.06), sepsis (RR 1.19, 95% CI 0.93–1.53; P = 0.17), malignancy (RR 0.79, 95% CI 0.51–1.24; P = 0.31) and cerebrovascular attack (RR 0.76, 95% CI 0.44–1.30; P = 0.31) were not significantly different in kidney transplantation patients with versus without SLE.ConclusionsComplications associated with kidney transplantation including mortality, graft failure and delayed graft function were not significantly higher in patients with SLE when compared with a control group. The causes of graft failure and mortality after kidney transplantation were also comparable in both groups. Therefore, kidney transplantation represents a promising treatment in patients with SLE with ESRD.

P27. Renal transplant patients at increased odds off many perioperative adverse events following lumbar laminotomy/discectomy

P27. Renal transplant patients at increased odds off many perioperative adverse events following lumbar laminotomy/discectomy

Model-informed dose optimization of mycophenolic acid in pediatric kidney transplant patients

PurposeWe aimed to develop and evaluate a population PK model of mycophenolic acid (MPA) in pediatric kidney transplant patients to aid MPA dose optimization.MethodsData were collected from pediatric kidney transplant recipients from a Dutch academic hospital (Radboudumc, the Netherlands). Pharmacokinetic model-building and model-validation analyses were performed using NONMEM. Subsequently, we externally evaluated the final model using data from another academic hospital. The final model was used to develop an optimized dosing regimen.ResultsThirty pediatric patients were included of whom 266 measured MPA plasma concentrations, including 20 full pharmacokinetic (PK) curves and 24 limited sampling curves, were available. A two-compartment model with a transition compartment for Erlang-type absorption best described the data. The final population PK parameter estimates were Ktr (1.48 h−1; 95% CI, 1.15–1.84), CL/F (16.0 L h−1; 95% CI, 10.3–20.4), Vc/F (24.9 L; 95% CI, 93.0–6.71E25), Vp/F (1590 L; 95% CI, 651–2994), and Q/F (36.2 L h−1; 95% CI, 9.63–74.7). The performance of the PK model in the external population was adequate. An optimized initial dose scheme based on bodyweight was developed. With the licensed initial dose, 35% of patients were predicted to achieve the target AUC, compared to 42% using the optimized scheme.ConclusionWe have successfully developed a pharmacokinetic model for MPA in pediatric renal transplant patients. The optimized dosing regimen is expected to result in better target attainment early in treatment. It can be used in combination with model-informed follow-up dosing to further individualize the dose when PK samples become available.

Synergistic Effect of Cytochrome P450 Family 3 Subfamily A Member 5 (CYP3A5) Genetic Variants in Tacrolimus Dose Determination in Indian Renal Transplant Patients

Synergistic Effect of Cytochrome P450 Family 3 Subfamily A Member 5 (<i>CYP3A5)</i> Genetic Variants in Tacrolimus Dose Determination in Indian Renal Transplant Patients

Diagnosis and Treatment of Skin Lesions in Renal Transplant Recipients: A Retrospective Review.

Immunosuppressive therapy is essential for to prevent graft rejection in renal transplant patients; however, it is associated with elevating the risk of several pathologies in these patients particularly infectious and neoplastic conditions. In this study, we explore the diagnosis and treatment of skin lesions in renal transplant patients. A retrospective chart review of 12 renal transplant recipients referred to plastic and reconstructive surgery with skin lesions from 2000 to 2020 was performed. The mean age of the 12 patients was 49.6 years. Time to plastic surgery after renal transplantation ranged between 1 and 16 years. Nine cases of basal cell carcinoma, 2 cases of squamous cell carcinoma, and 1 case of skin and soft tissue infection of the lower extremity and cutaneous extranodal NK/T-cell lymphoma, nasal type was observed. Flaps, skin grafts, and artificial dermis grafts constitute the main reconstructive methods. There were no postoperative infections or wound dehiscence. Cutaneous infections and skin malignancy account for most of the skin lesions developing after renal transplantation. Posttransplant lymphoproliferative disorder warrants equal attention and should not be disregarded. Early diagnosis and treatment significantly improve prognosis as patients with longer duration of transplant were found to have more aggressive tumors. Plastic and reconstructive surgery offers a safe therapeutic method of treatment in these cases.

Cancer Screening in Renal Transplant Recipients: Real-World Data.

Multiple international guidelines have endorsed cancer screening in renal transplant patients. This study aimed to describe a series of patients with post-transplant cancer and to report physicians' adherence to cancer screening guidelines. This is a retrospective study of cancer patients who had a history of renal transplant. Charts of patients who were treated at our institution between 2012 and 2023 were reviewed, patients' clinical data were collected. Thirty-nine patients were identified. The most common types of cancer were lymphoma (n = 9, 23%), squamous cell carcinoma (SCC) of the skin (n = 8, 20.5%), and breast (n = 6, 15.4%). The median age at diagnosis was 56.5 years (range: 16.9 - 70.2), family history of malignancy was depicted in 18 (46.2%) cases. Chart review and patients' questionnaire revealed that increased risk of malignancy was discussed in seven (18%) out of 39 recipients (P < 0.001) at time of transplant, and only three (7.7%, P < 0.001) patients were on post-transplant age-matched cancer screening. The increased risk of malignancy is a serious post-transplant complication. Lymphoma and non-melanoma skin cancer were the most common cancers. Most patients were not offered routine cancer screening; it is important to raise awareness among nephrologists and caregivers regarding the risk of post-transplant malignancy.

Family Environment, Social Support, and Health-Related Quality of Life in Adolescents Following Kidney Transplant.

Kidney transplantation is the treatment of choice for pediatric end-stage renal disease. Transplant recipients often have better neurocognitive, academic, and health-related outcomes. While there is some evidence that health-related quality of life (HRQOL) improves following kidney transplant, other studies have found adolescent transplant recipients report lower overall HRQOL than healthy peers. Current research has focused on individual-level factors affecting adjustment to organ transplant, warranting examination of HRQOL from a systems perspective. Family environment and social support contribute to a system of proximal relationships that are crucial in adolescents' development, making them important factors to study in relation to HRQOL post-transplant. The current study utilized archival data of adolescent renal transplant patients who completed surveys about their family environment, social support, and HRQOL during routine transplant clinic visits. Family cohesion, as well as social support from parents, classmates, and people in school, were positively correlated with HRQOL. Social support from people in school uniquely predicted variance in HRQOL, beyond the contribution of overall family environment after controlling for demographic factors. Relative to comparable adolescent samples, transplant recipients reported more optimal overall family environment, greater social support from teachers, and lower social support from close friends. Psychosocial interventions for adolescent kidney transplant recipients may be enhanced by collaborating with school professionals and further bolstering strengths in the family environment. Kidney transplant recipients may benefit from long-term intervention, as decreased HRQOL appears to persist years post-transplant.

Regulatory B Cells Expressing Granzyme B from Tolerant Renal Transplant Patients: Highly Differentiated B Cells with a Unique Pathway with a Specific Regulatory Profile and Strong Interactions with Immune System Cells.

The aim of our study was to determine whether granzyme B-expressing regulatory B cells (GZMB+ B cells) are enriched in the blood of transplant patients with renal graft tolerance. To achieve this goal, we analysed two single-cell RNA sequencing (scRNAseq) datasets: (1) peripheral blood mononuclear cells (PBMCs), including GZMB+ B cells from renal transplant patients, i.e., patients with stable graft function on conventional immunosuppressive treatment (STA, n = 3), drug-free tolerant patients (TOL, n = 3), and patients with antibody-mediated rejection (ABMR, n = 3), and (2) ex-vivo-induced GZMB+ B cells from these groups. In the patient PBMCs, we first showed that natural GZMB+ B cells were enriched in genes specific to Natural Killer (NK) cells (such as NKG7 and KLRD1) and regulatory B cells (such as GZMB, IL10, and CCL4). We performed a pseudotemporal trajectory analysis of natural GZMB+ B cells and showed that they were highly differentiated B cells with a trajectory that is very different from that of conventional memory B cells and linked to the transcription factor KLF13. By specifically analysing GZMB+ natural B cells in TOLs, we found that these cells had a very specific transcriptomic profile associated with a reduction in the expression of HLA molecules, apoptosis, and the inflammatory response (in general) in the blood and that this signature was conserved after ex vivo induction, with the induction of genes associated with migration processes, such as CCR7, CCL3, or CCL4. An analysis of receptor/ligand interactions between these GZMB+/- natural B cells and all of the immune cells present in PBMCs also demonstrated that GZMB+ B cells were the B cells that carried the most ligands and had the most interactions with other immune cells, particularly in tolerant patients. Finally, we showed that these GZMB+ B cells were able to infiltrate the graft under inflammatory conditions, thus suggesting that they can act in locations where immune events occur.

The Cost-effectiveness of Valganciclovir Prophylaxis Versus Preemptive Therapy in CMV R+ Kidney Transplant Recipients Over the First Year Posttransplantation.

In kidney transplant recipients with positive serology (R+) for the cytomegalovirus (CMV), 2 strategies are used to prevent infection, whose respective advantages over the other are still debated. This study aimed to evaluate the cost-effectiveness and cost utility of antiviral prophylaxis against CMV versus preemptive therapy, considering CMV infection-free survival over the first year posttransplantation as the main clinical outcome. Clinical, laboratory, and economic data were collected from 186 kidney transplant patients CMV (R+) included in the cohort study (85 patients who benefited from CMV prophylaxis and 101 from preemptive therapy). Costs were calculated from the hospital perspective and quality-adjusted life years (QALYs) using the EQ5D form. Using nonparametric bootstrapping, the incremental cost-effectiveness ratio (ICER) and cost utility were estimated (euros) for each case of infection avoided and each QALY gained for 1 y, respectively. Prophylaxis significantly decreased the risk of CMV infection over the first year posttransplantation (hazard ratio 0.22, 95% confidence interval = 0.12-0.37, P < 0.01). Compared with preemptive therapy, prophylaxis saved financial resources (€1155 per patient) and was more effective (0.42 infection avoided per patient), resulting in an ICER = €2769 per infection avoided. Prophylaxis resulted in a net gain of 0.046 in QALYs per patient and dominated over preemptive therapy with €1422 cost-saving for 1 QALY gained. This study shows that CMV prophylaxis, although considered as a more expensive strategy, is more cost-effective than preemptive therapy for the prevention of CMV infections in renal transplant patients. Prophylaxis had a positive effect on quality of life at reasonable costs and resulted in net savings for the hospital.

Impact of Renin-Angiotensin System Blockade on Mortality and Allograft Loss among Renal Transplant Recipients: A Systematic Review and Meta-Analysis.

The blockade of the renin-angiotensin system (RAS) has a beneficial effect on reducing the levels of proteinuria and blood pressure in patients with chronic kidney disease (CKD) and reduces the risk of developing end-stage kidney disease in CKD patients. Nonetheless, a debate persists regarding the impact of RAS inhibitors on outcomes such as mortality and graft survival in renal transplant patients. To assess the effect of RAS inhibitors on graft recipients in the past decade, we conducted a systematic review and meta-analysis. We searched Embase, PubMed, and the Cochrane Central Register of Clinical Trials from January 1, 2012, to August 1, 2022. We included 14 articles, comprising 5 randomized controlled trials (RCTs) and 9 cohort studies, including 45,377 patients. These studies compared patient or graft survival between an RAS inhibitor treatment arm and a control arm. The meta-analysis revealed that RAS blockade was significantly associated with lower mortality in cohort studies (risk ratio [RR] = 0.66, 95% confidence interval [CI]: 0.55-0.79), reduced allograft loss in cohort studies (RR = 0.62, 95% CI: 0.54-0.71), and significant changes in systolic blood pressure in RCTs. Subgroup analysis of the groups of interest (interventions involving RAS blockade, follow-up period of ≥5 years) showed consistently reduced mortality (RR = 0.67, 95% CI: 0.56-0.81) and reduced allograft loss (RR = 0.61, 95% CI: 0.54-0.70). Our results demonstrated that the application of RAS blockade among renal transplant recipients was associated with lower mortality and allograft loss in cohort studies but not in RCTs. More powered clinical trials are needed to evaluate the effects of RAS blockade in renal transplant recipients.