Improving prediction of tacrolimus concentration using a combination of population pharmacokinetic modeling and machine learning in chinese renal transplant recipients.

Aims: The population pharmacokinetic (PPK) model-based machine learning (ML) approach offers a novel perspective on individual concentration prediction. This study aimed to establish a PPK-based ML model for predicting tacrolimus (TAC) concentrations in Chinese renal transplant recipients. Methods: Conventional TAC monitoring data from 127 Chinese renal transplant patients were divided into training (80%) and testing (20%) datasets. A PPK model was developed using the training group data. ML models were then established based on individual pharmacokinetic data derived from the PPK basic model. The prediction performances of the PPK-based ML model and Bayesian forecasting approach were compared using data from the test group. Results: The final PPK model, incorporating hematocrit and CYP3A5 genotypes as covariates, was successfully established. Individual predictions of TAC using the PPK basic model, postoperative date, CYP3A5 genotype, and hematocrit showed improved rankings in ML model construction. XGBoost, based on the TAC PPK, exhibited the best prediction performance. Conclusion: The PPK-based machine learning approach emerges as a superior option for predicting TAC concentrations in Chinese renal transplant recipients.

Clinical Features and Prognostic Predictors in Patients with Renal Transplant Complicated by SARS-CoV-2 Infection, a Retrospective Single-Center Study.

Background: This study examines the clinical outcomes and prognostic factors of COVID-19 in renal transplant recipients. Given their immunosuppressed status, these patients are at higher risk of severe complications from COVID-19. The study aims to provide healthcare professionals with critical insights for diagnosing and managing this vulnerable population. Patients and methods: This retrospective cohort study included adult renal transplant recipients diagnosed with COVID-19. Data on demographics, medical history, laboratory results, and patient outcomes were analyzed to identify clinical characteristics and prognostic factors. Results: This study included 115 renal transplant recipients with COVID-19, predominantly male, with a mortality rate of 10.4% (12 deaths). The overall vaccination rate was 20%. Univariate analysis showed significant differences between survivors and non-survivors in initial serum creatinine levels, and percentages of neutrophils, monocytes, and lymphocytes, along with CRP levels on day 3. Additionally, CRP levels, hemoglobin, and platelet counts on day 7 also differed significantly. Multivariate analysis identified CRP levels on days 3 and 7, day 7 hemoglobin and platelet counts, and concurrent bacterial infections as independent risk factors for mortality. Conclusion: Elevated CRP levels, renal impairment, and bacterial co-infections play a significant role in the outcomes of COVID-19 in kidney transplant recipients. This study highlights the importance of monitoring these factors for early identification and management of high-risk patients.

Comprehensive Review of Urinary Tract Infections in Renal Transplant Recipients: Clinical Insights and Management Strategies.

Urinary tract infections (UTIs) pose a significant challenge in the care of renal transplant recipients. This comprehensive review explores this population's multifaceted landscape of UTIs, emphasizing the importance of early diagnosis and tailored management strategies. Renal transplant recipients face an elevated risk of UTIs due to immunosuppression, altered urinary tract anatomy, and complex comorbidities. Complications of UTIs can lead to graft dysfunction and systemic illness, underscoring the need for effective management. The emergence of multidrug-resistant uropathogens adds complexity to treatment, highlighting the importance of targeted antibiotic therapy. Antibiotics are the most commonly prescribed drugs for UTIs, with nitrofurantoin, fosfomycin, amoxicillin, and amoxicillin-clavulanate potassium being some of the commonly used antibiotics. However, the emergence of multidrug-resistant uropathogens has led to the exploration of alternative treatments, such as bacteriophage therapy, as a potential alternative against multidrug-resistant uropathogenic bacteria. Analgesics such as phenazopyridine can be prescribed to relieve discomfort associated with UTIs. Estrogen therapy has also been suggested as a potential treatment option for UTIs, particularly in postmenopausal women. Trimethoprim-sulfamethoxazole or trimethoprim is recommended as first-line therapy for uncomplicated UTIs. The choice of drug and therapy for UTIs depends on the severity of the infection, the causative organism, and the presence of antibiotic resistance. Preventive measures encompass pre-transplant evaluation, perioperative strategies, post-transplant follow-up, and vaccination. A multidisciplinary approach involving transplant specialists, infectious disease experts, pharmacists, and patient engagement is vital for successful care. The future of UTI management lies in ongoing research, exploring personalized medicine, novel therapies, and innovative prevention strategies. By implementing these strategies and advancing research, healthcare providers can improve graft and patient survival, enhancing the quality of care for renal transplant recipients.

Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies.

PURPOSE: This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of tacrolimus. METHODS: Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase were systematically searched from inception to August 2022. The outcomes were weight-adjusted daily dose and dose-adjusted trough concentration (C0/Dose). RESULTS: The study included 2931 renal transplant recipients from 18 publications. Weight-adjusted daily dose of CYP3A4*1/*1 carriers was 0.04 (WMD = 0.04, 95% CI: 0.02 to 0.06), 0.03 (WMD = 0.03, 95% CI: 0.02 to 0.05), 0.02 (WMD = 0.02, 95% CI: 0.01 to 0.03), or 0.02 mg/kg/day (WMD = 0.02, 95% CI: 0.00 to 0.04) higher than CYP3A4*22 carriers in Caucasians at 1 month, 3 months, 6 months, or 12 months post-transplantation. Conversely, C0/Dose was lower for CYP3A4*1/*1 carriers at 3 days (SMD = -0.35, 95% CI: -0.65 to -0.06), 1 month (SMD = -0.67, 95% CI: -1.16 to -0.18), 3 months (SMD = -0.60, 95% CI: -0.89 to -0.31), 6 months (SMD = -0.76, 95% CI: -1.49 to -0.04), or 12 months post-transplantation (SMD = -0.69, 95% CI: -1.37 to 0.00). Furthermore, C0/Dose of POR*1/*1 carriers was 22.64 (WMD = 22.64, 95% CI: 2.54 to 42.74) or 19.41 (ng/ml)/(mg/kg/day) (WMD = 19.41, 95% CI: 9.58 to 29.24) higher than POR*28 carriers in CYP3A5 expressers at 3 days or 7 days post-transplantation, and higher in Asians at 6 months post-transplantation (SMD = 0.96, 95% CI: 0.50 to 1.43). CONCLUSIONS: CYP3A4*22 variant in Caucasians restrains the metabolism of tacrolimus, while POR*28 variant in CYP3A5 expressers enhances the metabolism of tacrolimus for renal transplant recipients. However, further well-designed prospective studies are necessary to substantiate these conclusions given some limitations.

Neutrophil: Lymphocyte and Platelet: Lymphocyte ratios measured before transplantation and their correlation with new-onset diabetes post-transplantation in renal transplant recipients.

PURPOSE: Our goal was to evaluate the neutrophil:lymphocyte (NLR) and platelet:lymphocyte (PLR) ratios measured before transplantation and their correlation with new-onset diabetes after transplantation (NODAT) in renal transplant recipients. PATIENTS AND METHODS: We conducted our study in 324 adult patients consecutively admitted to Military Hospital 103, Ha Noi, Viet Nam, who received kidney allografts from living donors. These patients were followed-up during the first 2 years post-transplantation for NODAT. We examined the association between NLR and PLR measured prior to transplantation in patients with NODAT: NLR and PLR were calculated based on the results of the complete blood count. The criteria for diagnosis of a fully symptomatic NODAT case were based on the guidelines established by the American Diabetes Association and included fasting venous blood glucose and glycosylated hemoglobin A1c (HbA1c) levels, with or without an oral glucose tolerance test. RESULTS: The overall rate of NODAT during the two years after kidney transplantation was 13.6%. We found mean values of age and body mass index (BMI), and median values of NLR, PLR, high sensitivity C-reactive protein (hs-CRP) levels, and the arteriosclerosis ratio in the NODAT group to be significantly higher than those of the non-NODAT group (all p < 0.05). Furthermore, an adjusted multivariate regression analysis showed that age (area under the curve [AUC] = 0.727, p < 0.001), BMI (AUC = 0.846, p < 0.001), serum hs-CRP levels (AUC = 0.884, p < 0.001), NLR (AUC = 0.888; p < 0.001), and PLR (AUC = 0.818; p < 0.001) had predictive value for NODAT. CONCLUSION: NLR and PLR measured before transplantation were good predictors for NODAT in the first 2 years post-renal transplantation.

Risk factors for SARS-CoV-2 pneumonia among renal transplant recipients in Beijing Omicron wave.

The novel coronavirus disease-19 had become an unprecedented global health emergency, quickly expanding worldwide. Omicron (B.1.1.529), as a novel variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was initially identified in South Africa and Botswana. Renal transplant recipients (RTRs) are a special group and are more vulnerable to viral pneumonia. Thus, this study aimed to assess the incidence and risk factors of SARS-CoV-2 pneumonia that occurred in RTRs with Omicron infection. This single-center case-control study enrolled the RTRs who were diagnosed with SARS-CoV-2 infection by the SARS-CoV-2 nucleic acid test, which were divided into two groups according to the imaging features of SARS-CoV-2 pneumonia. The parameters were collected by questionnaires and analyzed using Statistical Product and Service Solutions. A total of 313 RTRs completed the questionnaires, and 131 were enrolled in this study with a mean age of 42.66 years. The incidence of SARS-CoV-2 pneumonia among the enrolled participants was 76.3%. The first symptoms included fever (89.3%), cough (93.1%), and expectoration (81.7%). From the comparison, the parameters such as age, gender, body mass index, lymphocyte count, and the percent of neutrophils and the basic serum creatinine before SARS-CoV-2 infection were significantly different between the two groups (P < 0.05). In multivariate analysis, age and the basic serum creatinine were independent risk factors for developing SARS-CoV-2 pneumonia (P < 0.05). Older RTRs with a high level of serum creatinine before SARS-CoV-2 infection were more at risk of developing SARS-CoV-2 pneumonia. More randomized controlled studies are needed.IMPORTANCEThis study aimed to assess the incidence and the risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia that occurred in renal transplant recipients (RTRs) with Omicron infection. In conclusion, older RTRs with a high level of serum creatinine before SARS-CoV-2 infection were more at risk of developing SARS-CoV-2 pneumonia and should be timely treated, in case of severe pneumonia.

Impact of an ultrasensitive Cytomegalovirus quantitative nucleic acid test on Cytomegalovirus detection and therapy in renal transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) infection has broad implications for morbidity and mortality in renal transplant recipients (RTR). Routine surveillance for CMV replication with PCR-based quantitative nucleic acid testing (qNAT) assays is standard practice in most transplant centers, but the impact of assay sensitivity on antiviral decision-making and virologic outcomes has not been studied. We investigated the effects of an ultrasensitive CMV qNAT assay on multiple clinical outcomes, including time to detection and duration of CMV DNAemia. METHODS: We conducted a single-center cohort study contrasting RTRs monitored with a qNAT with a higher lower limit of quantification (LLOQ >300 IU/mL) with those monitored with a more sensitive qNAT (LLOQ >35 IU/mL). Patients were stratified by donor (D)/recipient (R) CMV serostatus (D+/R-: high risk; any R+: moderate risk). CMV viral load monitoring was performed monthly post transplantation, with the primary outcomes being time to CMV DNAemia and its duration. RESULTS: Total 1382 patients were analyzed from 2014 to 2016 and 2019 to 2021. Moderate-risk RTRs monitored with the more sensitive assay experienced a greater hazard for the development of a first episode of CMV DNAemia (aHR: 1.95, 95% confidence interval [CI]: 1.55-2.46) and an average of 24 (95% CI: 16.40-31.98) additional days of DNAemia. There was no difference in CMV end-organ disease or 1-year all-cause mortality between moderate-risk RTRs. CONCLUSIONS: The more sensitive assay was associated with earlier detection and extended durations of CMV DNAemia in moderate-risk RTRs, without altering clinical outcomes. These findings inform optimal use of these assays and antiviral stewardship in RTRs. KEY SUMMARY: The use of ultrasensitive CMV qNAT assays in moderate-risk CMV renal transplant recipients is associated with earlier detection and longer durations of CMV DNAemia without impacting CMV end-organ disease or 1-year mortality.

Clinical Course of Candidate Renal Transplant Recipients Diagnosed With Prostate Cancer During Pre-transplant Screening Test.

BACKGROUND/AIM: Occasionally, candidate renal transplant recipients (RTRs) are incidentally diagnosed with prostate cancer (PCa) during pre-transplant screening examinations; however, their clinical course remains unclear. This study aimed to clarify the clinical course of RTR diagnosed with PCa during pre-transplant screening tests. PATIENTS AND METHODS: Between April 2008 and April 2022, 15 candidates for RTRs were newly diagnosed with PCa during the screening test. We analyzed the patients' treatment choices, initial treatment results, waiting duration for renal transplantation, and whether they finally underwent transplantation. RESULTS: The median patient age was 64 years (range=52-75 years). The median prostate-specific antigen level was 6.9 ng/ml (5.2-56.9 ng/ml). According to D'Amico risk stratification, one, 10, and four patients were at low, intermediate, and high risk, respectively. As for treatment choice, 13 patients chose surgery. Moreover, intensity-modulated radiotherapy and hormone therapy were chosen by one patient each. Of these, seven patients underwent transplantation, with a median waiting time from initial treatment to transplantation of 20.3 months (9.2-40.0 months). One patient discontinued transplantation owing to poor cancer control, four patients had donor issues (change in mind, aging, or disease), and one patient waited because pathological findings revealed locally invasive cancer. CONCLUSION: PCa diagnosis in candidate RTRs during the pre-transplant screening test impacts the candidate's clinical course.

Neurotrophin-4 and Brain-Derived Neurotrophic Factor Serum Levels in Renal Transplant Recipients with Chronic Pruritus.

INTRODUCTION: Chronic pruritus (CP) is a common symptom defined as a sensation that provokes the desire to scratch and which lasts for at least 6 weeks. CP remains a problem for up to 21.3% of renal transplant recipients (RTRs). Our research aimed to establish the possible association between serum levels of neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF) and the presence and intensity of CP in RTR. METHODS: The study was performed on a group of 129 RTRs, who were divided according to the presence or absence of pruritus in the previous 3 days. The assessment of pruritus was performed with the use of a numeric rating scale (NRS), 4-Item Itch Questionnaire (4IIQ), and Itchy Quality of Life (Itchy QoL). A total of 129 blood samples with a volume of 9 ml were drawn from RTRs during the monthly routine control. Serum levels (pg/mL) of NT-4 and BDNF were measured by the ELISA. RESULTS: Pruritic RTRs have statistically significantly higher serum concentrations of NT-4 serum level compared to non-pruritic RTRs (229.17 ± 143.86 pg/mL and 153.08 ± 78.19 pg/mL [p = 0.024], respectively). Moreover, a statistically significant difference between pruritic and non-pruritic RTRs with healthy controls was shown (p < 0.001 and p < 0.001, respectively). Although there was a numerically higher serum concentration of BDNF in pruritic RTRs (32.18 ± 7.31 pg/mL vs. 31.58 ± 10.84 pg/mL), the difference did not reach statistical significance. No statistically significant difference was also seen in BDNF serum levels between RTRs and healthy controls. Furthermore, there was a statistically significant, positive correlation between serum concentration of NT-4 and NRS score (p = 0.008, r = 0.357). CONCLUSIONS: The results indicate higher NT-4 serum concentration in RTRs with pruritus compared to RTRs without pruritus. Furthermore, the study revealed a statistically significant, positive correlation between the serum concentration of NT-4 and NRS score.

Association of Three Different Dietary Approaches to Stop Hypertension Diet Indices with Renal Function in Renal Transplant Recipients.

Several dietary indices assess the impacts of the Dietary Approaches to Stop Hypertension (DASH) diet on health outcomes. We explored DASH adherence and renal function among 85 Taiwanese renal transplant recipients (RTRs) in a cross-sectional study. Data collection included demographics, routine laboratory data, and 3-day dietary records. Three separate DASH indices, that defined by Camões (based on nine nutrients), that defined by Fung (using seven food groups and sodium), and that modified by Fung (as above but separated for men and women) were used. Renal function was ascertained through the estimated glomerular filtration rate (eGFR) from patients' medical records. Participants' mean age was 49.7 ± 12.6 years and eGFR was 54.71 ± 21.48 mL/min/1.73 m2. The three established DASH diet indices displayed significant correlations (r = 0.50-0.91) and indicated the nutritional adequacy of the diet. Multiple linear regressions indicated a significant positive association between higher DASH scores for each index and increased eGFR. In addition, RTRs in the highest DASH score tertile had higher eGFR rates than those in the lowest tertile, regardless of confounding variables. Adherence to a DASH-style diet correlated with better renal function among RTRs. Educating RTRs about the DASH diet may prevent graft function deterioration.

The pattern of cytomegalovirus replication in post-renal transplant recipients with pre-emptive therapy strategy during the 1st year of post-transplantation.

Objectives: The prevalence and reactivating pattern of cytomegalovirus (CMV) among renal transplant recipients in Sri Lanka is scarce. The study was aimed to describe the replication patterns of CMV in post-renal transplant recipients who were on pre-emptive therapy and identify the risk factors and time period for CMV reactivating during the 1st year of transplantation and provide an insight into the selection of pre-emptive therapy in the local setting. Methods: A retrospective and cohort study was conducted, enrolling renal transplant recipients who have completed routine 1-year follow-up for pre-emptive management at the National Hospital, Kandy, from January 2016 to January 2021. CMV quantitative polymerase chain reaction results and demographic data of enrolled recipients were analyzed to investigate the CMV replication pattern and risk factors. Categorical data were analyzed using Pearson's Chi-square test, considering P < 0.05 statistically significant. Continuous variables were presented as percentages. Results: Two hundred and fifty-one renal transplant recipients' data were included in the study. Of them, 75.70% were male patients, and the mean age of the study population was 43.25 years. CMV DNAemia incidence was 56.57% during the 1st year of post-renal transplantation. Only 9.16% had developed more than 104 IU/mL or significant DNAemia. Sex and donor type were not risk factors for CMV reactivation. However, the recipient's age was significantly associated with CMV viraemia among renal transplant recipients. Conclusion: Considering the low incidence of significant viraemia among the study population, pre-emptive treatment would be the cost-effective strategy for management of the post-renal transplant recipients in local settings.

Systematic Review of Calcineurin Inhibitors and Incidence of Skin Malignancies after Kidney Transplantation in Adult Patients: A Study of 309,551 Cases.

The purpose of this systematic review and meta-analysis was to compare the risk of non-melanoma skin cancer (NMSC) and melanoma development in renal transplant recipients who receive calcineurin inhibitors to that of patients treated with other immunosuppressive agents, and investigate the possible association between the type of maintenance immunosuppression and the incidence of NSMC and melanoma in this group of patients. The authors searched databases such as PubMed, Scopus, and Web of Science for articles that would help establish the influence of calcineurin inhibitors on skin cancer development. The inclusion criteria for the study consisted of randomized clinical trials, cohort studies, and case-control studies that compared patients who received kidney transplants and were treated with a calcineurin inhibitor (CNI), such as cyclosporine A (CsA) or tacrolimus (Tac), to those who received alternative immunosuppressants and did not receive a CNI. Seven articles were analyzed overall. The results revealed a correlation between CNI treatment in renal transplant recipients and increased total skin cancer risk (OR 1.28; 95% CI: 0.10-16.28; p < 0.01), melanoma risk (OR 1.09; 95% CI: 0.25-4.74; p < 0.01), and NMSC risk (OR 1.16; 95% CI: 0.41-3.26; p < 0.01). In conclusion, the calcineurin inhibitors used after kidney transplantation are associated with a higher risk of skin cancer-both non-melanoma and melanoma-when compared with other immunosuppressive therapies. This finding suggests that careful monitoring for skin lesions in post-transplant patients must be conducted. However, the decision on the kind of immunotherapy used should always be considered on an individual basis for each renal transplant recipient.

The Clinical Manifestation of Immunosuppressive Therapy as a Tool to Improve Immune Monitoring in Renal Transplant Recipients.

INTRODUCTION: Metrics for posttransplant immune monitoring to prevent over or under immunosuppression in renal transplant recipients (RTRs) are lacking. METHODS: We surveyed 132 RTRs, 38 in the first year posttransplant and 94 >1-year posttransplant, to study the clinical expression of immunosuppressive therapy. A questionnaire administered to these RTRs was divided into physical (Q physical) and mental (Q mental) symptoms. RESULTS: In multivariable models for the association between the calculated Q physical and Q mental scores and different clinical and biochemical variables in the 38 RTRs who filled out the questionnaire 130 times during the first year posttransplant, it was found that mycophenolic acid (MPA) and prednisone use increased the mean Q physical score by 0.59 (95% CI: 0.21-0.98, p = 0.002) and 0.53 (95% CI: 0.26-0.81, p = 0.00), respectively, while MPA use increased the mean Q mental score by 0.72 (95% CI: 0.31-1.12, p = 0.001). Among the 94 RTRs who each completed the questionnaire only once, the odds for the mean Q mental score to be above the median value were more than 3 times higher for RTRs treated versus non-treated with MPA (OR 3.38, 95% CI: 1.1-10.3, p = 0.03). MPA-treated RTRs had higher mean scores for questions related to sleep disorders (1.83 ± 1.06 vs. 1.32 ± 0.67 for not treated, p = 0.037), to difficulty falling asleep (1.72 ± 1.11 vs. 1.16 ± 0.5, p = 0.02), and to depression and anxiety. CONCLUSION: We concluded that prednisone and MPA use are associated with an increased Q physical and Q mental scores in RTRs. Routine monitoring of physical and mental status of RTRs should be implemented to improve the diagnosis of overimmunosuppression. Dose reduction or discontinuation of MPA should be considered in RTRs who report sleep disorders, depression, and anxiety.

Long-time Survival of a Renal Transplant Recipient With Metastatic Mucinous Tubular and Spindle Cell Carcinoma: A Case Report.

BACKGROUND/AIM: Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare histological type of renal cell carcinoma (RCC). There are few reports of MTSCC occurring in renal transplant recipients (RTRs). The aim of this study was to report a case of long-term survival of a RTR with metastatic MTSCC of the kidney with sarcomatoid changes. CASE REPORT: A 53-year-old male with a left retroperitoneal tumor was referred to our department. He had been receiving hemodialysis since 1991 and underwent kidney transplantation in 2015. Computed tomography (CT) revealed suspected RCC, and a radical nephrectomy was performed in June 2020. Pathological findings revealed MTSCC with sarcomatoid changes. After the surgery, multiple metastases appeared in the bilateral adrenals, skin, para-aortic lymph nodes, muscles, mesocolon, and liver. We treated the patient with metastasectomy, radiation therapy, and sequential systemic therapy with tyrosine kinase inhibitors (TKI). Two years after the initial surgery, the patient died of cancer while controlling its progression. CONCLUSION: We report a RTR with aggressive and metastatic MTSCC with sarcomatoid changes, resulting in a longer survival time relative to multimodal therapy.

Predictors and Adverse Outcomes of Acute Kidney Injury in Hospitalized Renal Transplant Recipients.

Data about in-hospital AKI in RTRs is lacking. We conducted a retrospective study of 292 RTRs, with 807 hospital admissions, to reveal predictors and outcomes of AKI during admission. In-hospital AKI developed in 149 patients (51%). AKI in a previous admission was associated with a more than twofold increased risk of AKI in subsequent admissions (OR 2.13, p < 0.001). Other major significant predictors for in-hospital AKI included an infection as the major admission diagnosis (OR 2.93, p = 0.015), a medical history of hypertension (OR 1.91, p = 0.027), minimum systolic blood pressure (OR 0.98, p = 0.002), maximum tacrolimus trough level (OR 1.08, p = 0.005), hemoglobin level (OR 0.9, p = 0.016) and albumin level (OR 0.51, p = 0.025) during admission. Compared to admissions with no AKI, admissions with AKI were associated with longer length of stay (median time of 3.83 vs. 7.01 days, p < 0.001). In-hospital AKI was associated with higher rates of mortality during admission, almost doubled odds for rehospitalization within 90 days from discharge and increased the risk of overall mortality in multivariable mixed effect models. In-hospital AKI is common and is associated with poor short- and long-term outcomes. Strategies to prevent AKI during admission in RTRs should be implemented to reduce re-admission rates and improve patient survival.

Risk stratification of renal transplant recipients using routine parameters: Implication of learning from SARS-CoV-2 into transplant follow-up program.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation. In the course of acute SARS-CoV-2 infection, various laboratory markers have been identified as predictors for high risk of mortality. AIM: To risk stratify renal transplant recipients (RTxR) using general demographic parameters, comorbidities and routine laboratory markers for the severity of the disease and its outcomes. We believe that learning about these routinely moni tored parameters can help us plan better strategies for the RTxR follow-up program. METHODS: This present study includes RTxR who acquired SARS-CoV-2 infection from March 2020 to February 2021. We recorded the basic demographics, comorbidities and routine laboratory markers. We investigated the impact of SARS-CoV-2 infection on RTxRs and risk-stratified the progression of disease severity and outcomes in terms of recovery or mortality. RESULTS: From 505 RTxRs in our renal transplant follow-up program, 29 (7.75%) RTxRs had PCR-positive SARS-CoV-2 infection. We recorded 8 deaths from SARS-CoV-2 infection giving an overall mortality rate of 1.6% but a significant 27.6% mortality in SARS-CoV-2 positive recipients. Age more than 68 years, non-Caucasian ethnicity and male gender were associated with a significant drop in survival probability; P ≤ 0.001. < 0.001 and < 0.0001 respectively. 87.5% of the deceased were diabetic; P ≤ 0.0.0001. Estimated glomerular filtration rate of less than 26 mL/min/1.73 m2, serum albumin less than 20 g/L, Hemoglobin less than 9.6 g/L and serum calcium less than 1.70 mmol/L were all associated with significantly increased risk of mortality; P = 0.0128, < 0.001, < 0.0001 and 0.0061 respectively. CONCLUSION: This study has identified some routinely used modifiable parameters in predicting a higher risk of mortality and morbidity. This knowledge can be used in RTxR follow-up programs by addressing these parameters early to help reduce the morbidity and mortality in RTxRs.

Changes in Dietary Nutrient Intake and Estimated Glomerular Filtration Rate over a 5-Year Period in Renal Transplant Recipients.

The scarcity of dietary guidance for renal transplant recipients (RTRs) raises concerns regarding obesity and associated comorbidities, including impaired renal function. This two-stage cross-sectional study examined longitudinal changes in dietary nutrient intake in the same individuals over a 5-year interval. This study involved two stages: T1 (September 2016 to June 2018) and T2 (July 2022 to August 2023). The average duration between the two data collection stages was 6.17 ± 0.42 (range 5.20-6.87) years. The study included 227 RTRs with an average age and time since transplant of 49.97 ± 12.39 and 9.22 ± 7.91 years, respectively. Of the 35 patients who participated in both phases, fewer than half met the recommended intakes for energy, dietary fiber, and most vitamins and minerals, as set in the Dietary Reference Intakes (DRIs) or by the Dietitian Association Australia (DAA). Over half exceeded the DRI recommended intake for total protein, and more than 80% of the protein consumed per kilogram of body weight exceeded the DAA's recommendations. In the T2 stage, the RTRs had a significantly higher blood urea nitrogen level, lower albumin level, and estimated glomerular filtration rate. These findings indicate that deteriorating dietary intake in RTRs can adversely affect their nutritional status and transplanted kidney function over a 5-year period.

Variants of HCMV UL18 Sequenced Directly from Clinical Specimens Associate with Antibody and T-Cell Responses to HCMV.

Around 80% of adults worldwide carry human cytomegaloviris (HCMV). The HCMV gene UL18 is a homolog of HLA class I genes and encodes a protein with high affinity for the NK and T-cell cytotoxicity inhibitor LIR-1. UL18 was deep sequenced from blood, saliva or urine from Indonesian people with HIV (PWH) (n = 28), Australian renal transplant recipients (RTR) (n = 21), healthy adults (n = 7) and neonates (n = 4). 95% of samples contained more than one variant of HCMV UL18, as defined by carriage of nonsynonymous variations. When aligned with immunological markers of the host's burden of HCMV, the S318N variation associated with high levels of antibody reactive with HCMV lysate in PWH over 12 months on antiretroviral therapy. The A107T variation associated with HCMV antibody levels and inflammatory biomarkers in PWH at early timepoints. Variants D32G, D248N, V250A and E252D aligned with elevated HCMV antibody levels in RTR, while M191K, E196Q and F165L were associated with HCMV-reactive T-cells and proportions of Vδ2- γδ T-cells-populations linked with high burdens of HCMV. We conclude that UL18 is a highly variable gene, where variation may alter the persistent burden of HCMV and/or the host response to that burden.

Metabolic and functional effects of exercise training in diabetic kidney transplant recipients.

BACKGROUND: Physical activity levels are significantly lower in kidney transplant (KT) recipients compared to the general population. The effects of exercise training in KT recipients with diabetes mellitus remain unclear, and so little is known about the role of increased exercise on cardiovascular risk and metabolic profile of KT patients. AIM: To investigate the effects of a 6-mo home-based exercise training program on functional capacity, glucose levels and lipid profile of diabetic KT patients. METHODS: In total, 21 type II diabetic KT recipients were randomly assigned into two groups: Exercise (n = 11, aged 52.9 ± 10.1 years) and control (n = 10, aged 53.01 ± 9.5 years). All participants at baseline and the end of the study underwent biochemical tests for fasting plasma glucose levels, glycated hemoglobin and lipid profile and cardiopulmonary exercise testing for maximum oxygen uptake [(VO2)peak] estimation. The exercise group followed a 6-mo supervised home-based aerobic and progressive resistance exercise program of moderate intensity 3 times per week, while the control group continued to receive usual care. RESULTS: At the end of the 6-mo study, the exercise group had significantly lower values in fasting plasma glucose by 13.4% (from 120.6 ± 28.9 mg/dL to 104.8 ± 21.9 mg/dL, P = 0.01), glycated hemoglobin by 1.5% (from 6.7% ± 0.4 to 6.6% ± 0.4, P = 0.01) and triglycerides by 8.5% (from 164.7 ± 14.8 mg/dL to 150.8 ± 11.6 mg/dL, P < 0.05) and higher values in high-density lipoprotein by 10.2% (from 51.4 ± 8.8 mg/dL to 57.2 ± 8.7 mg/dL, P < 0.05) and (VO2)peak by 4.7% (from 22.7 ± 3.3 to 23.8 ± 4.2, P = 0.02) than the control group. There were statistically significant differences between the two groups at the end of the study for fasting plasma glucose (decreased by 9.6%, P < 0.05), triglycerides (decreased by 4.5%, P = 0.04) and (VO2)peak (increased by 4.4%, P = 0.01). Finally, after training, there was a moderate, positive linear relationship between (VO2)peak and glycated hemoglobin in the exercise group (r = 0.408, P = 0.03). CONCLUSION: The results demonstrated that a 6-mo home-based mixed type exercise training program can improve the functional capacity, levels of glucose and lipid profile of diabetic KT recipients.