Infection In Renal Transplant Patients Research Articles

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.

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.

#1569 Cytomegalovirus (CMV) infection in renal transplant patients managed with early pre-emptive treatment

Abstract Background and Aims Human Cytomegalovirus (CMV) can cause significant morbidity in transplant recipients. Primary CMV infection in CMV seronegative recipients (R−) and reactivation of CMV in seropositive recipients (R+) post-transplant can lead to CMV end organ disease (EOD). At Royal Free Hospital (RFH), London, United Kingdom, CMV EOD is prevented through pre-emptive therapy (PET), which utilises quantitative real-time PCR (qPCR) in whole blood to monitor all transplant patients and guide therapeutic interventions (1). PET is started in D+R− transplant patients following the first detectable CMV DNA (≥200 copies/ml) in blood (2). For CMV seropositive patients, PET is started when CMV DNA is ≥3000 copies/ml. This differs from many transplant centres which provide CMV anti-viral prophylaxis for the first 3-6 months post-transplant to patients at high risk of developing CMV EOD. In this observational study, the effectiveness of our PET approach and differences in CMV viral replication kinetics was retrospectively analysed in renal transplant recipients of differing CMV serostatus. Method A retrospective review of results from electronic patient records and laboratory information management system for patients who underwent renal transplantation from April 2021 to January 2023 was conducted. Patients were divided into four groups based on organ donor and recipient CMV IgG serostatus (D+R−, D+R+, D−R+, D−R−). Those who were followed up for less than 90 days or had unknown donor serostatuses were excluded. Results A total of 227 patients who received renal transplantation between April 2021 to January 2023 were identified. Of which, 11% (25/227) were D+R−, 42.3% (96/227) were D+R+, 33% (75/227) were D−R+ and 13.7% (31/227) were D−R−. Within each group, 60% (15/25) of D+R−, 61.5% (59/96) of D+R+ and 48% (36/75) of D−R+ patients developed CMV viraemia during the monitoring period. Of CMV viraemic patients, all D+R− (15/15), 54.2% (32/59) of D+R+ and 27.8% (10/36) of D−R+ patients were treated with valganciclovir as per our PET protocol. None of the D−R− patients developed any CMV viraemia. The mean peak viral load for patients with viraemia requiring treatment with valganciclovir was 4772 copies/ml (range 210-30000 copies/ml) in D+R−, 5050 copies/ml (range 3000-30000 copies/ml) and 5050 copies/ml (range 3300-18000 copies/ml) in D+R+ and D−R+ groups respectively. The mean time to first viraemia was 59 days (range 15-332) for the D+R−, 40 days (range 7-177) for D+R+ and 43 days (range 15-91) for D−R+ patients. Furthermore, the mean duration of viraemia was 34 days for D+R−, 37.5 days for D+R+ and 30.5 days for D−R+ groups. 19 patients had CMV viraemia recurrence requiring re-treatment, 63%were D+R− (12/19), 32% were D+R+ (6/19) and 5% (1/19) were D−R+. Across all four groups, two patients developed CMV EOD. One D+R+ patient was found to have CMV in respiratory sample and one D−R+ patient had CMV on colon biopsy. One D+R− patient developed UL97 mutations (M460I and A594V) conferring ganciclovir resistance due to poor compliance and was treated with maribavir. Conclusion PET is a safe and effective approach which reduces the risk of CMV EOD and antiviral medication resistance in SOT patients. Our PET approach provides monitoring of all patients regardless of CMV serostatus thereby reducing the risk of CMV EOD in all patients by ensuring early treatment of viraemia.

Infective complications in the renal transplant recipients

Infections remain a common complication of solid-organ transplantation and are a major factor of morbidity and mortality in renal transplant recipients. The incidence of infection in renal transplant patients is directly related to the net immunosuppressive effect achieved and the duration of the administration of immunosuppressive therapy. The major types of infections can be categorized according to the time post-transplant during which they occur: in the first month after transplantation post-surgical bacterial infections and in the period from one to four months post-transplant opportunistic infections, overall cytomegalovirus; late infections, beyond 6-12 months, are community-acquired infections. Opportunistic infections (like Pneumocystis carini, Listeria monocytogenes, and Aspergillus fumigatus) most frequently occur in the first 12 months post-transplant and can be modulated by prior exposures and the use of prophylaxis.

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

Persistent Norovirus infection in a young patient with renal transplant: The challenging cost of immunosuppression and the negative impact on patient’s quality of life

Norovirus (NoV) is one of the most common causes of acute infectious gastroenteritis in the United States (US). The infection is typically short-lasting and self-limiting in immunocompetent hosts. Renal transplant recipients on immunosuppressive therapy are more prone to infectious gastroenteritis that can be caused by various common and opportunistic organisms. NoV infection in renal transplant patients presents as an acute diarrheal illness that may progress to a chronic infection with frequent relapses leading to adverse short-term complications (acute renal injury (AKI) and acute graft rejection from the reduction of the dose of immunosuppressive medications) and possibly long-term morbidities (malabsorption syndrome, and a decline in graft survival). The management of chronic NoV infections in renal transplant patients may be quite challenging, as no specific antiviral treatment is presently approved, and frequent adjustments of immunosuppressive therapy may be required in the setting of reduced renal clearance and the attempts to decrease immunosuppressive effects to enhance the viral clearance.Herein, the authors present a case of persistent NoV in a young female patient with a renal transplant that was associated with recurrent admissions with AKI, gross electrolyte disturbances, and significant weight loss. The relapsing NoV infection has negatively impacted the patient's quality of life and socioeconomic performance.

COVID-19 in Renal Transplant Patients – A Narrative Review

Abstract The World Health Organisation declared the novel coronavirus known as severe acute respiratory syndrome coronavirus 2 a pandemic in March 2020. This virus has led to the deaths of more than 6 million people worldwide. Besides causing pneumonia, COVID-19 is linked to multiple organ dysfunction, including the kidneys, especially in individuals whose immune systems are already compromised. Consequently, individuals who are currently on a waiting list for a kidney transplant or who have recently received a kidney transplant are at a significantly increased risk for developing acute kidney injury and are severely impacted by the COVID-19 infection. The pandemic has negatively affected the transplantation process and led to a decrease in the number of organ donations as well as the volume of renal transplants. This review summarises the outcomes of COVID-19 infection in renal transplant patients, its pathophysiology, the challenges faced by the transplant community, and the management of immunosuppression.

Incidence and risk factors for mucormycosis in renal transplant patients

BackgroundRenal transplant patients are at increased risk for mucormycosis. Diabetes, neutropenia, deferoxamine therapy, and immunosuppressive medications have been associated with increased risk of mucormycosis in studies of solid organ transplant...

A Current Review of the Etiology, Clinical Features, and Diagnosis of Urinary Tract Infection in Renal Transplant Patients.

Urinary tract infection (UTI) represents the most common infection after kidney transplantation and remains a major cause of morbidity and mortality in kidney transplant (KT) recipients, with a potential impact on graft survival. UTIs after KT are usually caused by Gram-negative microorganisms. Other pathogens which are uncommon in the general population should be considered in KT patients, especially BK virus since an early diagnosis is necessary to improve the prognosis. UTIs following kidney transplantation are classified into acute simple cystitis, acute pyelonephritis/complicated UTI, and recurrent UTI, due to their different clinical presentation, prognosis, and management. Asymptomatic bacteriuria (ASB) represents a frequent finding after kidney transplantation, but ASB is considered to be a separate entity apart from UTI since it is not necessarily a disease state. In fact, current guidelines do not recommend routine screening and treatment of ASB in KT patients, since a beneficial effect has not been shown. Harmful effects such as the development of multidrug-resistant (MDR) bacteria and a higher incidence of Clostridium difficile diarrhea have been associated with the antibiotic treatment of ASB.

Renal Transplants COVID-19 Infection with Different Presentations, Clinical Courses and Outcomes

We report five cases with different clinical presentations of COVID-19 infection in renal transplant patients. Initially a typical clinical presentation, in the form of CNS manifestations (amnesia, behavior change followed by left sided paresis) for the 1st case, GIT manifestations for the 2nd case and chest and cardiac manifestations for the 3rd case were presented. The other two cases similarly presented with chest manifestations but with different clinical courses. Our patients had a favorable outcome, which may provide a reference value for treating COVID-19 patients. © 2021, Ain Shams University Faculty of Medicine. All rights reserved.

Cytomegalovirus disease in post-renal transplant patients: An Indian experience - A prospective observational study

Background: Cytomegalovirus is an important viral pathogen causing infection in immunodeficient patient especially in solid organ transplant like renal transplant. This study aims to evaluate the prevalence and clinical impact of CMV infection in renal transplant patients in a tertiary care hospital in Northern India. Materials and Methods: 145 renal transplant patients were tested for cytomegalovirus DNA by polymerase chain reaction (PCR) and for presence of IgM and IgG antibody against cytomegalovirus by ELISA. PCR amplified product were detected by Agarose gel electrophoresis. Results: Out of 145 transplant patients CMV Viremia was detected by PCR in 16(11.0%) patients. Two patients died in the study period in which one patient had HBV and other had HCV infection. IgM antibody against CMV was detected in one out of 145 donors while IgG anti-CMV antibody was detected in all 145 donors and recipients by ELISA. Two out of 145 transplant recipients had positive CMV PCR in pre-transplant period, and both had positive CMV PCR in post-transplant period. Out of sixteen positive patients histopathology changes of CMV disease was found in 2 patients (12.5%). Conclusion: Cytomegalovirus disease is major cause of morbidity and mortality in renal transplant patients. PCR to detect specific CMV genome sequences is important tool for early diagnosis and specific anti viral therapy. In our study out of 145 transplant patients, CMV Viremia was detected by PCR in 16 patients (11.0%). Two patients in the study period died, in which one patient had HBV and other had HCV infection, remaining patients survived with varying range of serum creatinine levels. Diagnostic histological changes of CMV is seen only in minority of cases(12.5%) who are positive by PCR for CMV.

COVID-19 Infection in Renal Transplant Patients: Early Report From India.

Introduction:COVID –19 has gripped the whole world and patients with comorbidities especially kidney ailments are at higher risk of developing severe disease. Among kidney disease, transplant patients are the most vulnerable group. Information on coronavirus disease 2019 (COVID-19) in kidney transplant patients is very limited.Methods:An observational study was conducted on 20 kidney transplant patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction from April to June 2020.Results:The majority of cases were males (85%). The median age of the patients was 50 years (interquartile range [IQR] 40.75–60.75). Diabetes and hypertension were present in 55% and 95% of patients, respectively. Coronary artery disease was present in three patients (15%). The median time from transplant to COVID-19 testing was 54 months (IQR 36–105). Chronic allograft nephropathy was found in 35% of patients. The mean baseline creatinine was 1.71 mg/dL. The most common symptom was fever (80%). Acute Kidney Injury was seen in 60% of patients with a mean creatinine of 2.60 mg/dL. Based on severity, 50% of patients had mild disease, 25% moderate disease, and the remaining 25% had severe disease. All 20 patients were on oral steroids, calcineurin inhibitors (18 on tacrolimus and two on cyclosporine), and antimetabolite (19 on mycophenolate mofetil and one on azathioprine). Antimetabolite agents were stopped in all patients and tacrolimus was stopped in severe cases (25%). Hydroxychloroquine was given in 15 patients (75%). Fifteen patients (75%) recovered while five (25%) died.Conclusion:Kidney transplant recipients infected with COVID-19 have high mortality.

Norovirus Infection in Renal Transplant Patients with Chronic Diarrhea

Diarrhea is not uncommon in immunocompromised patients We report here four renal transplant patients in whom a molecular testing panel for gastrointestinal pathogens revealed positive test for norovirus.

Imaging spectrum of pulmonary infections in renal transplant patients.

In the post renal transplant setting, pulmonary infections comprise an important set of complications. Microbiological diagnosis although specific is often delayed and insensitive. Radiography is the most common and first imaging test for which patient is referred, however it is relatively insensitive. HRCT is a very useful imaging tool in the scenario where radiography is negative or inconclusive and high clinical suspicion for infection is present. HRCT features vary among the various pathogens and also depend on the level of immunocompromise. Certain HRCT findings are characteristic for specific pathogens and may help narrow diagnosis. In this review article, we will summarize the imaging findings of various pulmonary infections encountered in post renal transplant patients.

SUN-302 EFFICACY AND SAFETY OF ANTI-HUMAN T-LYMPHOCYTE IMMUNOGLOBULIN IN SUPPRESSION ABSOLUTE LYMPHOCYTE, CD3, CD4 AND CD8 COUNTS IN PATIENTS UNDERGOING RENAL TRANSPLANT

The objective of our study was to assess changes in absolute lymphocyte, CD3, CD4, CD8 counts, CD4:CD8 ratio, serum creatinine levels and incidence of viral and other infections in renal transplant patients receiving anti-human T-lymphocyte globulin (ATLG). In a single-center, retrospective, observational study, data of renal transplant patients was screened to identify patients treated with ATLG. ATLG was administered with a mean dose 5 mg/kg in three divided doses on a day before transplant and day 1 and day 2 post-transplant with. Blood samples were collected in EDTA vial on day 1 and day 5 for immunodeficiency panel testing. Changes in absolute lymphocytes count (aLC), absolute CD3 (aCD3), absolute CD4 (aCD4), absolute CD8 (aCD8) counts, CD4:CD8 ratio and serum creatinine were noted. Also, the incidence of bacterial, viral or any other infections as well as graft dysfunction or rejection were noted. In 30 patients treated with ATLG, mean age was 42.0±14.1 years and 80% were males. Etiology of chronic kidney disease was unknown in majority (86.7%) patients. HLA mismatch of 3 or more was seen in 61% patients. Significant reductions in aLC (1068.9±488.4 to 472.6±443.2, p<0.0001), aCD3 (790.8±405.8 to 249.5±305.4, p<0.0001), aCD4 (476.8±293.6 to 141.4±168.3, p<0.0001) and aCD8 (282.2±145.8 to 102.0±134.2, p<0.0001) counts were seen in post-transplant period. Change in CD4:CD8 ratio was also significant (p=0.046). Mean serum creatinine at discharge was 0.98±0.36 mg/dL, which changed to 1.06±0.31 at 1 month (n=29, p=0.109), 1.1±0.39 at 2 month (n=24, p=0.210), 1.26±0.49 at 3 months (n=18; p=0.040) and 1.33±0.31 at 6 months (n=8; p=0.081). Urinary tract infection (majority due to Escherichia coli) was observed in 30% patients. One patient each had delayed graft function and mild acute cellular rejection (at 5th month). No complications of viral infections were noted. Pre-transplant use of ATLG is associated with significant reduction in absolute counts of lymphocytes, CD3, CD4, CD8 cells, change in CD4:CD8 ratio and with preservation graft function over 6 months. There is no increase in incidence of viral infections. Larger, prospective studies are necessary to confirm the findings.

Clinically significant drug‐drug interaction between tacrolimus and fluconazole in stable renal transplant recipient and literature review

Clinical use of fluconazole against fungal infections in renal transplant patients is complicated by the potentially marked and unpredictable drug-drug interactions (DDIs). We report a case of tacrolimus-fluconazole DDI in a stable renal transplant recipient and describe the mechanism, magnitude and duration of this DDI through a literature review. A 38-year-old woman experienced a 9.1-fold increase in dose-normalized tacrolimus trough level (trough concentration/weight-normalized daily dose) and an 87% decrease in weight-normalized daily dose (daily dose/body weight) in the treatment of documented Candida albicans oesophagitis by fluconazole. After discontinuation of fluconazole for 161day, a 26% reduction in weight-normalized daily dose was required to maintain therapeutic exposure. Oral fluconazole has a more significant impact on its drug interactions with tacrolimus than intravenous fluconazole. Gene screening for CYP3A5 6986 A>G and ABCB1 3435 C>T in organ transplant recipients may help in preventing DDI and facilitating tacrolimus dose adjustment.

Platelet-to-Lymphocyte Ratio as a Potential Indicator of Infection-Associated Emergency Visits of Renal Transplant Recipients.

Infection-associated emergency department use in renal transplant recipients has been increasing as solid-organ transplant has become a more common treatment method for chronic kidney failure. Platelet-to-lymphocyte ratio has been demonstrated to be significantly elevated in nosocomial infections in patients treated at intensive care units and is positively correlated with duration of hospital stay. In this study, we aimed to determine whether the platelet-to-lymphocyte ratio could be used as an indicator of infection in renal transplant patients presenting to emergency departments. This case-control retrospective study included data from between May 2015 and February 2018. We used the patient information management system to review patient medical records and laboratory test results of study participants. Our study included 156 adults in the patient group (recipients with infection) and 170 adults in the control group (recipients without infection). We observed significant differences between patient and control groups in terms of the number of days of hospital stay; leukocyte, neutrophil, and lymphocyte counts; the platelet-to-lymphocyte ratio; and C-reactive protein levels. We plotted receiver operating characteristic curves to determine the sensitivity and specificity of the platelet-to-lymphocyte ratio along with C-reactive protein. The areas under the curve were 0.892 for C-reactive protein and 0.707 for the platelet-to-lymphocyte ratio. For systemic inflammation, platelet-to-lymphocyte ratio can be used in conjunction with other biomarkers as an indicator of inflammation in renal transplant recipients who present with infection-associated causes to emergency departments.

Host and pathogen factors in Klebsiella pneumoniae upper urinary tract infections in renal transplant patients.

To analyse the role of virulence factors (VFs) and host in Klebsiella pneumoniae upper urinary tract infections (UTIs) in renal transplant (RTx) recipients. Clinical and demographic data were registered prospectively. Phylogenetic background of K. pneumoniae isolates was analysed by PCR melting profiles (MP) and the following VFs genes: fimH-1, uge, kpn, ycfM, mrkD, rmpA, magA, hlyA, cnf-1, irp-1, irp-2, fyuA, entB, iutA, iroN by PCR. We studied urine cultures and clinical data from 61 episodes of K. pneumoniae UTI in 54 RTx recipients. There were 32 cases of AB (53%), 10 cases of lower UTI (16%), 19 cases of AGPN (31%), including six cases of bacteraemia. In total, 74 % of strains were extended-spectrum beta-lactamase+, and there were two carbapenemase-producing strains. PCR MP typing showed a diverse population with 52 different genetic profiles of K. pneumoniae. Analysis of the DNA profiles indicated 45 unrelated, unique genotypes and 7 related (16 isolates from 15 patients) genotypes. Urine flow impairment emerged as an independent predictor of K. pneumoniae upper UTIs (OR 14.28, CI 2.7-75.56, P 0.002), while we did not find any association between the profile of VFs and developing upper UTIs. The prevalence of the uge gene was lower in RTx patients on everolimus when compared to isolates from patients not receiving mTOR inhibitors (33.3 % vs 82.8 % P<0.05). K. pneumoniae upper UTI may be a marker of urine flow impairment. Bacterial VFs could not discriminate between upper and lower UTIs. However, immunosuppression may influence the selection of particular VFs.

Evaluation of the relationship between perioperative urine culture and postoperative urinary tract infections in renal transplant patients

Aim: The aim of the study was to determine the prevalence and risk factors of bacterial urinary tract infection (UTI) in patients undergoing renal transplantation and to evaluate the possible bacterial agents that colonize the bladder in patients with or without micturition beforehand.Material and Methods: A total of 89 renal transplant patients were included in the study. Demographic characteristics of the patients such as age and gender, as well as the presence of micturition before transplantation, clinical findings, urine culture, and agents that showed growth were all retrospectively analyzed and the relevant data were recorded.Results: Of the total 89 patients, 17 (19.10%) developed a urinary tract infection within 12 months after transplantation. Eight of these patients required hospitalization for treatment, while four had at least two infection episodes. Escherichia coli and Klebsiella pneumonia were the two most common causative agents. A comparison of the groups with and without UTI revealed that micturition before transplantation was not a factor that affected the development of UTI (p > 0.05).Conclusion: Because UTI represents a severe problem for renal transplant patients, it must be evaluated in all patients. No correlation was found between preoperative micturition and postoperative UTI.

SAT-335 - Incidence of hepatitis E infection in renal transplant patients in The Netherlands

SAT-335 - Incidence of hepatitis E infection in renal transplant patients in The Netherlands