Estimated Renal Metabolomics at Reperfusion Predicts One-Year Kidney Graft Function

Renal transplantation is the gold-standard procedure for end-stage renal disease patients, improving quality of life and life expectancy. Despite continuous advancement in the management of post-transplant complications, progress is still needed to increase the graft lifespan. Early identification of patients at risk of rapid graft failure is critical to optimize their management and slow the progression of the disease. In 42 kidney grafts undergoing protocol biopsies at reperfusion, we estimated the renal metabolome from RNAseq data. The estimated metabolites’ abundance was further used to predict the renal function within the first year of transplantation through a random forest machine learning algorithm. Using repeated K-fold cross-validation we first built and then tuned our model on a training dataset. The optimal model accurately predicted the one-year eGFR, with an out-of-bag root mean square root error (RMSE) that was 11.8 ± 7.2 mL/min/1.73 m2. The performance was similar in the test dataset, with a RMSE of 12.2 ± 3.2 mL/min/1.73 m2. This model outperformed classic statistical models. Reperfusion renal metabolome may be used to predict renal function one year after allograft kidney recipients.

Bacterial and Fungal Co-infections with SARS-CoV-2 in Solid Organ Recipients, A Retrospective Study

Background SARS-CoV-2, a novel corona virus, has caused clusters of fatal pneumonia worldwide. Immune compromised patients are among the high risk groups with poor prognosis of the disease. The presence of bacterial or fungal co-infections with SARS-CoV-2 is associated with increased mortality. Methods The electronic data of the liver and kidney recipients, hospitalized in COVID-19 intensive care unit in an 8-month period in 2020 were retrospectively assessed. The documented bacterial or fungal infections alongside with outcome and risk factors were recorded and analyzed by binary logistic regression model and multivariate analyses. Results Sixty-Six liver and kidney recipients were included this study. Twenty one percent of the patients had at least one episode of co-infection during their COVID-19 course. Bacterial and fungal co-infections contributed to a significantly higher mortality. Urine and sputum were the most common sites of pathogen isolation (45.45 % and 36.36%; respectively). The majority of infections were caused by vancomycin- resistant Enterococci (30%). Escherichia coli stood in the next position with 23.3%. Prior hospitalization and high does corticosteroid use were associated with co-infections (p=0<0.001 and p=0.02; respectively.)Conclusions Bacterial and fungal co-infections with COVID-19 are more prevalent in solid organ recipients compared to the general population. Prior hospitalizations and use of broad-spectrum antimicrobial agents lead to emergence of multi-drug resistant pathogens in this susceptible patient population. Early detection and treatment of co-infections as well as antibiotic stewardship is recommended in solid organ recipients.

HEPATITIS E VIRUS MONITORING RESULTS AND ITS LABORATORY SCREENING ALGORITHM

Background. Individual cases of viral hepatitis E are recorded in the Republic of Belarus annually indicating the need for the pathogen monitoring at both the population and reservoir levels. Objective. To consolidate the monitoring data on hepatitis E virus over the period of 2018 - 2021, as well as to work out an effective algorithm for its laboratory screening. Material and methods. As part of the study, 345 samples were analyzed, including 227 human biological samples, 37 samples of biological materials of domestic pigs, 22 samples of food and 59 samples of waste water. Results. According to the results of serum diagnostics, in the group of kidney recipients (n = 29), the detection rate of IgM and IgG to hepatitis E virus was 6.9% [0.85%; 23.03%] and 17.2% [7.13%; 35, 02%] respectively; in the group of patients with pregnancy pathology (n = 44) - 6.8% [1.68%; 18.89%] and 11.4% [4.5%; 24.43%] respectively. In patients with acute hepatitis of unknown etiology (n = 26), antiviral IgM was not detected, while the frequency of antiviral IgG detection reached 7.7% [1.02%; 25.26]. In control group (blood donors, n = 53) IgM and IgG were detected in 1.9% [0.6%; 10.88%] and 5.7% [1.35%; 15.97] of those examined respectively. Hepatitis E virus RNA was detected in 8 human biological samples (3.8%) from kidney recipients. The identified hepatitis E viruses were represented by genotype GIII and belonged to a previously unidentified subgenotype (GIIIa - GIIIi). In the studied samples of biological material from pigs, as well as in samples of food and waste water, hepatitis E virus RNA was not detected. Conclusions. An algorithm for hepatitis E virus laboratory screening has been developed and tested. Its section concerning the diagnosis of viral hepatitis E is set out in the Instructions for use "Algorithm for laboratory diagnosis of viral hepatitis E" (No. 148-1220 from January 28, 2021).

Understanding Patients’ and Living Donors’ Kidney Paired Donation Educational Experiences and Recommendations for Improvement

Introduction Educating potential kidney patients and living donors about the risks and benefits of kidney paired donation to ensure they make informed decisions is complex. This study aimed to increase understanding of patients’ and donors’ decision-making about donation, the educational content they received, and their recommendations for educational improvements. Method We conducted a mixed methods study, including semistructured interviews and quantitative surveys, with 43 participants (25 living donors; 18 kidney recipients). Findings Participants reported that the benefits of paired donation motivated them to participate (ie, helping multiple people, receiving a transplant sooner, flexible timing of donation). Although deciding to participate in paired donation was a systematic, logical, and carefully considered process for some. For most, it was a quickly made, often emotion-based decision. Paired donation educational content on different topics varied, with recipients reporting receiving less information than donors about donor protections and processes to ameliorate the challenges faced, such as broken swaps and chains, and delays in matching. Those who faced challenges requested more information about donor protections and support during and after paired donation. Although many acknowledged their transplant coordinators’ helpfulness, participants also recommended being more proactive in learning about kidney paired donation and speaking to former donors and recipients beforehand. Discussion Standardized, health literate educational content addressing the gaps and variability in education received may help increase paired donation informed decision-making.

The Psychosocial Adjustment of Kidney Recipients in Canada's Kidney Paired Donation Program

Introduction: Kidney paired donation programs have been implemented globally. The involvement of at least 2 donors in these programs might exacerbate recipients’ debt of gratitude and guilt, worries about the donor's health, and worries about graft failure documented by previous studies. However, there is an absence of research on the psychosocial implications of kidney paired donation. This study aimed to provide an in-depth examination of recipients’ experience of kidney paired donation, with a focus on psychosocial adjustment. Methods/Approach: Individual interviews were conducted with 8 recipients who received a transplant through Canada's Kidney Paired Donation program. Data was analyzed using Interpretative Phenomenological Analysis. Findings: Four themes emerged: (a) an emotionally charged relationship with the known donor, (b) optimal distance regulation in the relationship with the anonymous donor, (c) kidney paired donation as a series of ups and downs, and (d) multilayered gratitude. Discussion: Findings are considered in relation to extant literature. Issues relevant to the transplant community's clinical and research efforts to provide kidney recipients responsive care are discussed.

Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients

Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely CYP3A4, CYP3A5, MDR1 and POR genes, has been evaluated in diverse populations. However, the impact of these polymorphisms on drug disposition is not well established in Latin American populations. Using TaqMan® probes, we determined the allelic frequency of seven variants in CYP3A4, CYP3A5, MDR1 and POR in 139 Chilean renal transplant recipients, of which 89 were treated with CsA and 50 with TAC. We tested associations between variants and trough and/or 2-hour concentrations, normalized by dose (C0/D and C2/D) at specific time points post-transplant. We found that CYP3A5*3/*3 carriers required lower doses of TAC. In TAC treated patients, most CYP3A5*3/*3 carriers presented higher C0/D and a high proportion of patients with C0 levels outside the therapeutic range relative to other genotypes. These results reinforce the value of considering CYP3A5 genotypes alongside therapeutic drug monitoring for TAC treated Chilean kidney recipients.

Evaluation of the effectiveness of prophylactic strategies for cytomegalovirus infection in pediatric kidney recipients

Cytomegalovirus (CMV) infection is the most severe viral infection in renal transplant recipients, which can occur in the post-transplant period in both adult and pediatric recipients. Developing and applying an effective prevention and treatment strategy for pediatric renal graft recipients is a priority. Objective: to compare the effectiveness of the protocols used for the prevention of CMV infection in pediatric kidney transplant recipients.Materials and methods. The study enrolled 118 patients who underwent primary kidney transplantation at Shumakov National Medical Research Center of Transplantology and Artificial Organs. Based on retrospective analysis, all recipients were divided into two groups, depending on the prophylactic strategy after kidney transplantation. The followup period for pediatric kidney recipients ranged from 108 to 1803 (623.5 ± 379.5) days. CMV infection activity was monitored by polymerase chain reaction.Results. The frequency of CMV infection activation episodes at 3 and 6 months was independent of the prophylaxis strategy used. The recurrence rate of CMV infection one year after surgery was significantly lower (p = 0.037) with Strategy 2. No cases of CMV syndrome or CMV disease, graft dysfunction, or chronic rejection associated with CMV infection were reported. Increasing the dose of antiviral drugs in Strategy 1 did not increase the risk of cytotoxicity and nephrotoxicity, which are reversible (creatinine levels were not significantly different in the study groups at 3, 6, 12 months, p = 0.542, p = 0.287, p = 0.535, respectively). The incidence of kidney graft rejection did not increase in patients with lower doses of immunosuppressants in Strategy 2.Conclusion. Both prophylactic strategies are effective in pediatric kidney recipients. However, the choice of a strategy depends on the individual characteristics of the patient and requires a personalized approach.