Changes in T and B cell subsets in end stage renal disease patients before and after kidney transplantation

BACKGROUND: The incidence of kidney transplantation performed in elderly patients has increased steadily recently. Higher risk of infection and mortality, but lower rate of rejection, are reported in older kidney transplant patients. This study aims to analyze the effect of transplantation on aging of T and B cells in kidney transplant patients, with the emphasis on age and Cytomegalovirus (CMV) latency. RESULTS: We included 36 patients before and after (median 2.7 years) kidney transplantation and 27 age- and sex-matched healthy controls (HC). T and B cell subsets were measured by flow cytometry, with a focus on aged T cells (CD28-), and age associated B cells (ABCs, CD19 + CD21-CD11c+). Three years after transplantation a significant increase of total T cells among the lymphocytes was found compared to pre-transplantation and HC. Among the T cells CD4+ cells were decreased, especially naïve CD4+ cells and regulatory T cells. Total CD8+ cell proportions were increased, and proportions of naïve CD8+ cells were significantly decreased after transplantation, while CD8+ effector memory T cells re-expressing CD45RA were increased. CD28− T cells were significantly higher compared to HC after transplantation, especially in CMV seropositive patients. B cells were significantly decreased, while among B cells memory B cells and especially ABCs were increased after transplantation. CONCLUSIONS: After transplantation T and B cell subsets change towards more terminally differentiated memory cells compared to age-matched HC. Proportions of aged T cells and ABCs were associated with CMV serostatus. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-021-00254-9

Diagnostic accuracy of depression questionnaires in adult patients with diabetes: a systematic review and meta-analysis

Importance Comorbid depression is common among patients with diabetes and has severe health consequences, but often remains unrecognized. Several questionnaires are used to screen for depression. A systematic review and meta-analysis regarding the diagnostic accuracy of depression questionnaires in adults with diabetes is unavailable. Objective To conduct a systematic review and meta-analysis to evaluate the diagnostic accuracy of depression questionnaires in adults with type 1 or type 2 diabetes. Data sources PubMed, Embase and PsycINFO were searched from inception to 28 February 2018. Study selection Studies were included when the diagnostic accuracy of depression questionnaires was assessed in a diabetes population and the reference standard was a clinical interview. Data extraction and synthesis Data extraction was performed by one reviewer and checked by another. Two reviewers independently conducted the quality assessment (QUADAS-2). Diagnostic accuracy was pooled in bivariate random effects models. This study is reported according to PRISMA-DTA and is registered with PROSPERO (CRD42018092950). Main Outcome(s) and measure(s) Diagnostic accuracy, expressed as sensitivity and specificity, of depression questionnaires in an adult diabetes population. Results A total 6,097 peer-reviewed articles were screened. Twenty-one studies (N= 5,703 patients) met the inclusion criteria for the systematic review. Twelve different depression questionnaires were identified, of which the CES-D (n=6 studies) and PHQ-9 (n=7 studies) were the most frequently evaluated. Risk of bias was unclear for multiple domains in the majority of studies. In the meta-analyses, five (N= 1,228) studies of the CES-D (≥16), five (N= 1,642) of the PHQ-9 (≥10) and four (N=822) of the algorithm of the PHQ-9 were included in the pooled analysis. The CES-D (≥16) had a pooled sensitivity of 85.0% (95%CI, 71.3-92.8%) and a specificity of 71.6% (95%CI, 62.5-79.2%); the PHQ-9 (≥10) had a sensitivity of 81.5% (95%CI, 57.1-93.5%) and a specificity of 79.7% (95%CI, 62.1-90.4%). The algorithm for the PHQ-9 had a sensitivity of 60.9% (95%CI, 52.3-50 90.8%) and a specificity of 64.0% (95%CI, 53.0-93.9%). Conclusions and relevance This review indicates that the CES-D had the highest sensitivity, whereas the PHQ-9 had the highest specificity, although confidence intervals were wide and overlapping. The algorithm for the PHQ-9 had the lowest sensitivity and specificity. Given the variance in results and suboptimal reporting of studies, further high quality studies are needed to confirm the diagnostic accuracy of these depression questionnaires in patients with diabetes

Immune response to varicella-zoster virus before and after renal transplantation

Background: Herpes zoster (HZ) risk is high in renal transplant recipients. Vaccination prior to transplantation may provide a useful strategy for the prevention of HZ in the posttranplantation period. However, it is not known whether immunity to varicella-zoster virus (VZV) is affected due to treatment surrounding transplantation. Methods: Both humoral and cellular immunity to VZV were determined prior to and 2-3 years after renal transplantation in 60 adult patients, and 62 matched healthy controls. VZV-specific cellular immunity was measured by an interferon gamma (IFN gamma) enzyme-linked immunospot (ELISpot) assay and by analyzing T-cell functionality using flowcytometry. VZV-IgG levels were measured using an in-house glycoprotein enzyme-linked immunosorbent assay (gpELISA). Results: Using paired analysis, it was determined that numbers of IFN gamma-producing cells did not change after transplantation, but were significantly lower in transplant recipients after transplantation than in controls (p = 0.028). Patients in whom the post-transplant period was complicated by rejection or any acute infection (excluding HZ) had a lower number of IFN gamma-producing cells than patients who did not. VZV IgG levels did not differ from controls, but a significant decrease was observed after transplantation (p <0.0001). Conclusions: VZV-specific cellular immunity, which is essential in the prevention of HZ, did not markedly change in patients following renal transplantation. This suggests that preventive vaccination before transplantation may be beneficial. Our results extend knowledge on VZV immunity after transplantation, vital when considering strategies for the prevention of HZ in these patients

Informing evaluation of a smartphone application for people with acquired brain injury: a stakeholder engagement study

Background Brain in Hand is a smartphone application (app) that allows users to create structured diaries with problems and solutions, attach reminders, record task completion and has a symptom monitoring system. Brain in Hand was designed to support people with psychological problems, and encourage behaviour monitoring and change. The aim of this paper is to describe the process of exploring the barriers and enablers for the uptake and use of Brain in Hand in clinical practice, identify potential adaptations of the app for use with people with acquired brain injury (ABI), and determine whether the behaviour change wheel can be used as a model for engagement. Methods We identified stakeholders: ABI survivors and carers, National Health Service and private healthcare professionals, and engaged with them via focus groups, conference presentations, small group discussions, and through questionnaires. The results were evaluated using the behaviour change wheel and descriptive statistics of questionnaire responses. Results We engaged with 20 ABI survivors, 5 carers, 25 professionals, 41 questionnaires were completed by stakeholders. Comments made during group discussions were supported by questionnaire results. Enablers included smartphone competency (capability), personalisation of app (opportunity), and identifying perceived need (motivation). Barriers included a physical and cognitive inability to use smartphone (capability), potential cost and reliability of technology (opportunity), and no desire to use technology or change from existing strategies (motivation). The stakeholders identified potential uses and changes to the app, which were not easily mapped onto the behaviour change wheel, e.g. monitoring fatigue levels, method of logging task completion, and editing the diary on their smartphone. Conclusions The study identified that both ABI survivors and therapists could see a use for Brain in Hand, but wanted users to be able to personalise it themselves to address individual user needs, e.g. monitoring activity levels. The behaviour change wheel is a useful tool when designing and evaluating engagement activities as it addresses most aspects of implementation, however additional categories may be needed to explore the specific features of assistive technology interventions, e.g. technical functions

External ureteric stent versus internal double J stent in kidney transplantation:a retrospective analysis on the incidence of urological complications and urinary tract infections

INTRODUCTION: Urologic complications (UCs) and urinary tract infections (UTIs) are common after kidney transplantation. Intraoperative stent placement at the vesicoureteric anastomosis reduces UC risk, but increases UTI risk.METHODS: In 2014 our stenting protocol changed from external ureteric stent (ES) to internal double J stent (DJ). We retrospectively studied the occurrence of UCs and UTIs in relation to ES or DJ in 697 kidney recipients.METHODS: An ES was used in 403 patients (57.8%), in 294 (42.2%) a DJ. ES was removed 7-12 days and DJ 3-4 weeks post-operative. Induction immunosuppression was the same in both groups. Primary outcomes at 6 months follow-up were UC (urinary leakage/ureter stenosis) and UTI; they were related to stenting procedure and clinical and transplant characteristics. The incidence of UCs was similar for ES (8.4%) and DJ (6.8%), p=0.389. ES use was a significant risk factor for UTI (OR 1.69 (1.15-2.50), p=0.008). Post-transplant hospitalization was significantly shorter in the DJ group. Despite more acute rejection episodes with ES (ES/DJ: 16.4%/6.1%, p&lt;0.001), no clinical relevant differences in graft outcomes existed.DISCUSSION: A DJ is, compared to ES, associated with a lower incidence of UTIs and comparable occurrence of UCs and is therefore the preferred technique for stenting the vesicoureteric anastomosis.</p

Torquetenovirus Serum Load and Long-Term Outcomes in Renal Transplant Recipients

Following transplantation, patients must take immunosuppressive medication for life. Torquetenovirus (TTV) is thought to be marker for immunosuppression, and TTV-DNA levels after organ transplantation have been investigated, showing high TTV levels, associated with increased risk of infections, and low TTV levels associated with increased risk of rejection. However, this has been investigated in studies with relatively short follow-up periods. We hypothesized that TTV levels can be used to assess long term outcomes after renal transplantation. Serum samples of 666 renal transplant recipients were tested for TTV DNA. Samples were taken at least one year after renal transplantation, when TTV levels are thought to be relatively stable. Patient data was reviewed for graft failure, all-cause mortality and death due to infectious causes. Our data indicates that high TTV levels, sampled more than one year post-transplantation, are associated with all-cause mortality with a hazard ratio (HR) of 1.12 (95% CI, 1.02-1.23) per log10 increase in TTV viral load, (p = 0.02). Additionally, high TTV levels were also associated with death due to infectious causes (HR 1.20 (95% CI 1.01-1.43), p = 0.04). TTV levels decrease in the years following renal transplantation, but remain elevated longer than previously thought. This study shows that TTV level may aid in predicting long-term outcomes, all-cause mortality and death due to an infectious cause in renal transplant patients sampled over one year post-transplantation

Smoking, Alcohol Intake and Torque Teno Virus in Stable Kidney Transplant Recipients

Torque Teno Virus (TTV) is a non-pathogenic virus that is highly prevalent among kidney transplant recipients (KTRs). Its circulating load is associated with an immunological status in KTR and is considered a promising tool for guiding immunosuppression. To allow for optimal guidance, it is important to identify other determinants of TTV load. We aimed to investigate the potential association of smoking and alcohol intake with TTV load. For this cross-sectional study, serum TTV load was measured using PCR in stable kidney transplant recipients at ≥1 year after transplantation, and smoking status and alcohol intake were assessed through questionnaires and measurements of urinary cotinine and ethyl glucuronide. A total of 666 KTRs were included (57% male). A total of 549 KTR (82%) had a detectable TTV load (3.1 ± 1.5 log 10 copies/mL). In KTR with a detectable TTV load, cyclosporin and tacrolimus use were positively associated with TTV load (St. β = 0.46, p &lt; 0.001 and St. β = 0.66, p &lt; 0.001, respectively), independently of adjustment for potential confounders. Current smoking and alcohol intake of &gt;20 g/day were negatively associated with TTV load (St. β = -0.40, p = 0.004 and St. β = -0.33, p = 0.009, respectively), independently of each other and of adjustment for age, sex, kidney function, time since transplantation and calcineurin inhibitor use. This strong association of smoking and alcohol intake with TTV suggests a need to account for the smoking status and alcohol intake when applying TTV guided immunosuppression in KTR. </p