Renal Transplant Patients Research Articles

Aptitude of Uropathogenic Escherichia coli in Renal Transplant Recipients: A Comprehensive Review on Characteristic Features, and Production of Extended Spectrum β-Lactamase.

Urinary tract infection is the most common infection in almost half of the renal transplant patients. The development of UTI in these patients may progress to bacteremia, acute T cell-mediated rejection, impaired allograft function, or allograft loss, along with the increased risk of hospitalization and death. Among various pathogens implicated, Uropathogenic E. coli (UPEC), especially sequence type 131 (ST131), is the most virulent and multidrug-resistant pathogen. High antimicrobial resistance to most β-lactam antibiotics, mediated by extended spectrum β-lactamases (ESBLs) produced by UPEC, is a challenge in the clinical management of UTIs in kidney transplant recipients. Indeed, multidrug resistance to β-lactam antibiotics is a direct consequence of ESBL production. Resistance to other antibiotics such as aminoglycosides, fluoroquinolones, and trimethoprim-sulphamethoxazole has also been reported in ESBLs-producing UPEC, which reduces the therapeutic options, rising healthcare-associated costs and subsequently leads to renal failure or even graft loss. In this review, we aimed to discuss the post-transplant risk factors of UTI, UPEC virulence factors (VF), and the related factors including quorum sensing, and stress resistance genes. Furthermore, we searched for the current treatment strategies and some of the alternate approaches proposed as therapeutic options that may affirm the treatment of ESBL-producing UPEC.

Repurposing HLA genotype data of renal transplant patients to prevent severe drug hypersensitivity reactions.

Introduction: Specific alleles in human leukocyte antigens (HLAs) are associated with an increased risk of developing drug hypersensitivity reactions induced by abacavir, allopurinol, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, or flucloxacillin. Transplant patients are genotyped for HLA as a routine practice to match a potential donor to a recipient. This study aims to investigate the feasibility and potential impact of repurposing these HLA genotype data from kidney transplant patients to prevent drug hypersensitivity reactions. Methods: A cohort of 1347 kidney transplant recipients has been genotyped in the Leiden University Medical Center (LUMC) using next-generation sequencing (NGS). The risk alleles HLA-A*31:01, HLA-B*15:02, HLA-B*15:11, HLA-B*57:01, and HLA-B*58:01 were retrieved from the NGS data. Medical history, medication use, and allergic reactions were obtained from the patient's medical records. Carrier frequencies found were compared to a LUMC blood donor population. Results: A total of 13.1% of transplant cohort patients carried at least one of the five HLA risk alleles and therefore had an increased risk of drug-induced hypersensitivity for specific drugs. HLA-A*31:01, HLA-B*15:02, HLA-B*57:01, and HLA-B*58:01 were found in carrier frequencies of 4.61%, 1.19%, 4.46%, and 3.35% respectively. No HLA-B*15:11 carrier was found. In total nine HLA-B*57:01 carriers received flucloxacillin and seven HLA-B*58:01 carriers within our cohort received allopurinol. Discussion: Our study shows that repurposing HLA genotype data from transplantation patients for the assignment of HLA risk alleles associated with drug hypersensitivity is feasible. The use of these data by physicians while prescribing drugs or by the pharmacist when dispensing drugs holds the potential to prevent drug hypersensitivity reactions. The utility of this method was highlighted by 13.1% of the transplant cohort patients carrying an actionable HLA allele.

Machine Learning Models for Predicting Personalized Tacrolimus Stable Dosages in Pediatric Renal Transplant Patients

Tacrolimus, characterized by a narrow therapeutic index, significant toxicity, adverse effects, and interindividual variability, necessitates frequent therapeutic drug monitoring and dose adjustments in renal transplant recipients. This study aimed to compare machine learning (ML) models utilizing pharmacokinetic data to predict tacrolimus blood concentration. This prediction underpins crucial dose adjustments, emphasizing patient safety. The investigation focuses on a pediatric cohort. A subset served as the derivation cohort, creating the dose-prediction algorithm, while the remaining data formed the validation cohort. The study employed various ML models, including artificial neural network, RandomForestRegressor, LGBMRegressor, XGBRegressor, AdaBoostRegressor, BaggingRegressor, ExtraTreesRegressor, KNeighborsRegressor, and support vector regression, and their performances were compared. Although all models yielded favorable fit outcomes, the ExtraTreesRegressor (ETR) exhibited superior performance. It achieved measures of −0.161 for MPE, 0.995 for AFE, 1.063 for AAFE, and 0.8 for R2, indicating accurate predictions and meeting regulatory standards. The findings underscore ML’s predictive potential, despite the limited number of samples available. To address this issue, resampling was utilized, offering a viable solution within medical datasets for developing this pioneering study to predict tacrolimus trough concentration in pediatric transplant recipients.

The Use of Diffusion Tensor Imaging in the Identification of Acute Rejection and Chronic Allograft Nephropathy After Renal Transplantation.

Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). Prospective. Seventy-seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well-functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). 1.5 T/T2-weighted imaging and DTI. The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. One-way analysis of variance; correlation analysis; independent-sample t-test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P-value <0.05. The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 μmol/L vs. 82.3 ± 20.9 μmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. 2 TECHNICAL EFFICACY: Stage 2.

The effect of tacrolimus conversion from immediate- to extended-release formulation on renal function in renal transplant patients: a meta-analysis.

Objective: Tacrolimus formulation affects the outcomes of a renal transplant, while the effect of its immediate- to extended-release conversion remains controversial. This meta-analysis aimed to compare the renal function before and after tacrolimus immediate- to extended-release conversion in renal transplant patients. Methods: PubMed, Cochrane, Embase, CNKI, CQVIP, and Wanfang databases were searched for articles regarding the effect of tacrolimus conversion from immediate- to extended-release formulation on renal function in renal transplant patients. The data on serum creatinine (Scr) or the estimated glomerular filtration rate (eGFR) before and after conversion were extracted and analyzed. Results: Ten studies with 743 renal transplant patients were included. Scr was reduced after conversion versus before conversion [mean difference (MD) (95% confidence interval (CI)): -8.00 (-14.33; -1.66) μmol/L, p = 0.01]. However, eGFR only showed an increased trend after conversion versus before conversion (MD (95% CI): 2.21 (-1.62, 6.03)mL/min/1.73m2, p = 0.26) but without statistical significance. Furthermore, in patients with a follow-up duration ≥48 weeks, Scr was decreased after conversion versus before conversion (p = 0.005), but eGFR remained unchanged (p = 0.68). However, in patients with a follow-up duration <48weeks, both Scr (p = 0.36) and eGFR (p = 0.24) were not different before conversion versus after conversion. Moreover, publication bias risk was low, and robustness assessed by sensitivity analysis was generally good. Conclusion: This meta-analysis favors studies indicating that the conversion of tacrolimus from an immediate-release to an extended-release formulation could improve the kidney function to some extent in renal transplant patients, and this advancement may be related to the administration period.

Histiocytic sarcoma in renal transplant patients: a literature review

BackgroundHistiocytic sarcoma (HS) is defined as neoplasm resembling morphological and immunophenotypic characteristics of mature histiocytes. It is a rare form of lymphoid neoplasms. Despite advances in treatment and diagnosis of histiocytic sarcoma, majority of cases had poor prognosis due to progressive nature of the disease. In the following article, all reported cases of histiocytic sarcoma in renal transplant patients are reviewed.MethodsIn our literature review, all relevant reports were collected electronically by entering the necessary keywords. A Boolean approach using Medical Subject Heading (MeSH) keywords was implemented. After establishing the inclusion/exclusion criteria, article titles and abstracts were evaluated by Systematic Reviews and Meta-Analyses (PRISMA) standards for 2020. All cases of histiocytic sarcoma in renal transplant patients were included.ResultBased on our inclusion and exclusion criteria 4 case reports were yielded in this review. Two were males and 2 were females with the mean age of 42.25 years. Fever was the most common symptom. Although tumor originated from the native kidney on one patient, the site of the primary tumor was thorax, oropharynx, and transplanted kidney in the rest. Metastasis was detected in all cases. Prednisone was used for all cases. EBV was positive in 2 cases and negative in one of them. Histology was diagnostic and similar in all cases. Immunohistochemistry was done for 3 cases. Although chemotherapy was done for 3 patients, all 4 cases ended in mortality.ConclusionDespite the fact that neoplasms are post renal transplant complications, histiocytic sarcoma is a scarce and fatal entity in such patients. Histological and immunohistochemistry tests are the corner stone in diagnosis of histiocytic sarcoma.

An unexpected cause of refractory thrombocytopenia in post renal transplant patient

Post renal transplant patient often present with cytopenias including thrombocytopenia, this could be multifactorial including the immunosuppressive drugs, viral infections. Patient need immediate supportive treatment. The underlying etiology needs to be identified and treated. One of the less suspected cause is opportunistic infection like disseminated histoplasmosis. Progressive disseminated histoplasmosis is an uncommon opportunistic infection, largely affecting immunocompromised individuals, among organ transplant patients most commonly occur in post kidney transplant and patients on calcinurin inhibitor. The initial manifestation are fever, weight loss, hepatosplenomegaly, thrombocytopenia to an acute, rapidly fatal course causing resp. failure, shock, coagulopathy and multiorgan failure. Diagnosis can we made by histoplasma antigen assay or demonstration of histoplasma among tissue and bone marrow biopsy. Treatment include Intravenous amphotericin B with Long term itraconazole. We present an interesting case of disseminated histoplasmosis in post renal transplant patient presented with rashes, bleeding manifestation and severe thrombocytopenia, interestingly thrombocytopenia

Immunology of THymectomy And childhood CArdiac transplant (ITHACA): protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children

IntroductionPaediatric heart transplant patients are disproportionately affected by Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) compared with other childhood solid organ recipients. The drivers for this disparity remain poorly understood....

Follow-Up of 29 Years of Renal Transplant - A Case Report

Introduction: With the increasing longevity of renal transplant patients, the long-term morbidities of these patients have also increased. Thus, a multidisciplinary team is needed to follow-up on these cases and adequately detect and manage the complications. Furthermore, pregnancy rates have increased in this set of patients. Case Report: In this report, we discuss briefly the posttransplant period of a female patient who had spontaneous conception with two live births and had complications such as recurrent tuberculosis, skin cancers, and chronic diarrhea. However, the patient is leading an active life even after 29 years posttransplant. Conclusion: Pregnancy is less reported in renal transplant patients, but it needs a multidisciplinary approach to the management. Furthermore, early detection and management of posttransplant complications are of utmost importance and needs extreme vigilance and care.

Outcomes of and indications for renal transplantation in patients with von Hippel Lindau disease

Introduction and objectiveVon Hippel-Lindau (VHL) is a hereditary cancer syndrome characterized by bilateral, multifocal renal masses. The cumulative impact of extirpative surgery can depreciate renal function and render patients anephric. In the larger end-stage renal disease population, renal transplant offers both excellent quality of life and functional renal replacement. This case control study aims to examine and compare oncologic and functional outcomes of patients who have undergone renal transplant as renal replacement therapy (RRT) to those who remain anephric. MethodsPatient charts were retrospectively reviewed of patients with germline testing confirmed VHL between 1980 and 2022 for transplant, all prior surgical history (within and outside the NCI), renal function and graft outcomes. Overall survival (OS) was determined from years after radical nephrectomy, and graft time was defined as years of graft function from initial transplant until failure or patient death. Graft survival was determined as time between transplant(s) to last follow up. Kaplan-Meier analysis was conducted to compare graft times of anephric VHL patients to those with transplanted kidneys. ResultsA total of 23 VHLD patients were identified as either anephric or candidates for transplant. Out of this cohort, 11 total VHLD received 12 total kidney grafts. Median wait time from nephrectomy to transplant was 22.6 months (IQR: 1.02–40.25 months). Median age at transplant was 32 years (IQR: 23–54 years). OS at 5 and 10 years of anephric patients who did not receive a transplant was 33% and 16.7%, respectively. OS rates of the transplant cohort at 10, 15, and 20 years were 91%, 78%, and 58% years, respectively. Median graft time was 161 months (IQR: 56–214 months). Graft survival at 10, 15, and 20 years was 69.8%, 69.8%, and 26.2%, respectively. ConclusionsWe demonstrate that transplant recipients have decreased mortality with no difference in cancer recurrence compared to those who do not receive renal transplant for RRT. This data can aid in informing providers of the optimal window for early RRT planning in VHL, while also improving patient counseling.

Disseminated histoplasmosis with refractory thrombocytopenia in a renal transplant patient.

Disseminated histoplasmosis with refractory thrombocytopenia in a renal transplant patient.

Oral 11 - Long-term outcomes of renal transplantation in patients with end-stage renal disease (ESRD) due to nephrolithiasis

Oral 11 - Long-term outcomes of renal transplantation in patients with end-stage renal disease (ESRD) due to nephrolithiasis

Anesthetic management for renal transplant in patients with grade III diastolic dysfunction: case reports

BackgroundLeft ventricular diastolic dysfunction is frequently noticed in patients with multiple co-morbidities. Echocardiography is used to determine the presence of diastolic dysfunction and to grade its severity. In left ventricular diastolic dysfunction, the ventricular diastolic distensibility, filling, or relaxation is abnormal; however, the left ventricular ejection fraction may be normal or decreased.Case presentationWe present anesthetic management of two patients with diastolic dysfunction grade III for renal transplant. During declamping in renal transplant, high central venous pressures are required for adequate perfusion of the transplanted kidney. In the operation theater standard monitors including NIBP, SpO2 and five lead ECG were attached. An arterial line (radial) and central line (right internal jugular) were established for IBP and CVP monitoring. Infusions of furosemide and dopamine were started. Nitrogycerine and milrinone infusions were prepared but were not required intraoperatively. Both the patients were extubated at the end of surgery.ConclusionsIncreased incidence of major adverse cardiovascular events has been reported in surgical patients having grade III diastolic dysfunction. Hemodynamic instability and fluid overload in this set of patients are known to generate pulmonary edema.

Ultrasound-guided microwave ablation for tertiary hyperparathyroidism in patients with renal transplantation

Objective To explore the safety and efficacy of ultrasound-guided microwave ablation (MWA) for tertiary hyperparathyroidism (THPT) in patients with renal transplantation (RT). Methods In total, fifteen patients with THPT after renal transplantation who underwent MWA were enrolled in the study. The pre- and post-MWA intact parathyroid hormone (iPTH), serum calcium, phosphorus, creatinine, urea nitrogen and estimated glomerular filtration rate (eGFR) values were compared. Results A total of 38 parathyroid hyperplastic nodules in 15 RT patients were treated with ultrasound-guided MWA. The mean (median, range) size of the hyperplastic parathyroid nodules was 11.5 mm (11 mm, 5–25 mm), and the average (median, range) ablation time was 163.5s (121 s, 44–406 s). The average levels of serum iPTH and calcium at 1 d, 7 d, 1 month, 3 months, 6 months, 1 year post-MWA and at the end of follow-up were significantly lower than those pre-MWA (all p < 0.05). Compared with the pre-MWA value (0.76 mmol/L), the serum phosphorus levels at 1 d post-MWA (0.63 mmol/L) were significantly decreased, and those at 7 d, 1 month, 3 months, 6 months, 1 year post-MWA and at the end of follow-up were significantly increased, but all were within the normal range. There was no significant difference in serum creatinine and eGFR pre-MWA and post-MWA. No major MWA-related complications occurred. Conclusion Ultrasound-guided MWA shows potential as a viable treatment for THPT in RT patients. However, further studies are required to confirm its safety and effectiveness in larger cohorts of longer duration.

Cervical Cytology Findings in Renal Transplant Patients and Comparison of These Findings with Normal Population

Long-term immunosuppressive therapy increases the likelihood of renal transplant patients developing cervical cancer. We aimed to analyze the results of cervical cytology in renal transplant patients, compare these findings to those of the normal population, and determine the risk factors linked to the development of squamous intraepithelial lesions. Our analysis involved a retrospective study of hospital records from January 2000 to April 2018, encompassing 140 female renal transplant patients. A control group of 280 women with normal health status was selected and matched based on age and the cervical cytology procedure. The cervical cytology findings of the patients were re-evaluated using the Bethesda 2014 criteria. Of the total of 420 patients, 37 patients had epithelial cell abnormalities; including 32 (86.5%) patients in the renal transplant group and 5 (13.5%) control group (p ≤ 0.001). Sixty-two patients had infections; including 44 (71%) patients in the renal transplant group and 18 (29%) control group (p ≤ 0.001). We revealed that the development of squamous intraepithelial lesions was associated with factors such as having an immunologic disease as the primary renal disease, undergoing re-transplantation, and the presence of acute rejection (p ≤ 0.05). Cervical cytology screening plays a crucial role in detecting preinvasive lesions. The incidence of epithelial cell abnormalities is significantly higher in renal transplant patients compared to the normal population. Regular cervical cytology follow-up is vital for the early detection and prevention of cervical cancer progression in transplant recipients.

Poster 3 - Perioperative and long-term outcomes of renal transplantation in patients with cystic fibrosis

Poster 3 - Perioperative and long-term outcomes of renal transplantation in patients with cystic fibrosis

Early-term results of coronary artery bypass grafting in renal transplant patients

Early-term results of coronary artery bypass grafting in renal transplant patients

Poster 4 - Association between ureteric stents and urinary tract infections in renal transplant patients

Poster 4 - Association between ureteric stents and urinary tract infections in renal transplant patients

Fine-Needle Aspiration Biopsy Findings of the Thyroid Gland in Renal Transplant Patients.

For patients with end-stage renal disease, thyroid diseases are common due to altered hormone excretion and transport, and for renal transplant recipients this is due to immunosuppressive drugs. We investigated the prevalence of thyroid disorders, including thyroid cancer, by fine-needle aspiration biopsy in kidney transplant candidates and recipients and estimated the outcomes. For 305 thyroid fine-needle aspiration biopsies performed from January 2000 to December 2020 in patients with end-stage renal disease, we recorded patient demographics, thyroid ultrasonography, and biopsy findings. Of biopsy results from 305 patients, 272 (89.2%) were benign, 24 (7.9%) showed atypia of undetermined significance/follicular lesion of undetermined significance, 2 (0.7%) had suspicion for malignancy, and 7 (2.3%)were malignant.Thyroid surgery was performed for 13 patients with benign results, 6 with atypia of undetermined significance/follicular lesion of undetermined significance, 2 with suspicion for malignancy, and 7 with malignancy. In 13 patients with benign cytology, the histopathology finding was also benign in lobectomy specimens. In 6 patients with atypia of undetermined significance/follicular lesion of undetermined significance, the final diagnosis was papillary thyroid carcinoma in 3 patients, adenomatous hyperplasia in 2 patients, and Hurthle cell adenoma in 1 patient. For all 9 patients for whom fineneedle aspiration biopsy was suspicious for malignancy or malignant, histopathologic examination showed papillary thyroid carcinoma in total thyroidectomy materials. Among 12 papillary thyroid carcinoma patients, 4 underwent renal transplant after thyroidectomy, and survival for these 4 patients was 116.25 ± 29.30 months after transplant without tumor recurrence or distant metastases. Thyroid diseases are more frequent in patients with end-stage renal disease or renal transplant versus the normal population and also affect morbidity and mortality at higher rates in these patients. Fine-needle aspiration biopsy is a useful diagnostic modality in evaluation and treatment of thyroid nodules in both kidney transplant candidates and recipients.

Prevalence and Modifiable Factors for Holistic Non-Adherence in Renal Transplant Patients: A Cross-Sectional Study.

In renal transplant recipients, compliance with medical therapy is vital. Non-adherence is considered a risk factor for worst outcomes in kidney recipients, with attributed outcomes of 64% for graft loss and 80% for late acute rejection. Most literature defines adherence as self-based immunosuppression compliance but does not consider other relevant factors such as consult and procedure compliance. Therefore, this study aims to describe adherence prevalence in kidney transplant recipients and the factors related to non-adherence. This cross-sectional study included 1030 renal transplant patients followed by Colombiana de Trasplantes between January 2019 and July 2021. Sociodemographic and clinical variables were obtained based on clinical records. The mental-health group diagnosed holistic adherence in a semi-structured interview. The diagnosis considered medication intake failure, frequency and number of failures to medical controls or other procedures, suspicious non-adherence behaviors, and serum levels of immunosuppressants. A bivariate followed a descriptive analysis, and a forward logistic regression was performed for non-adherence. Patients had a median of 47 years, and 58.1% were male. Non-adherence was presented in 30.7% of patients. The non-adherence patients were younger, with a higher prevalence of males, single, divided transplant care, had a longer time after transplantation, psychopathological diagnosis, and more reinforcement education by only nursing. Older age and multidisciplinary reinforcement education were protective factors. On the other hand, poor social support, psychopathology diagnosis, and longer time after transplant presented as non-adherence risk factors. Holistic non-adherence was diagnosed in approximately one-third of renal transplant recipients. Its definition included more than just medication non-compliance and could identify more non-adherent patients. Notably, there is a need to consider the related factors in the health follow-up and encourage future research in modifiable factor interventions aiming to increase adherence and achieve better outcomes for renal transplant patients.