Serologic responses to T cell-dependent vaccinations are severely attenuated in patients with ESRD, but the reasons for this is unknown. In this study, a detailed analysis of antigen-specific T cell responses was performed. Patients on hemodialysis and age-and gender-matched healthy control subjects were vaccinated with hepatitis B surface antigen (HBsAg), antigen-specific CD4 ϩ T cells were monitored at regular intervals with intracellular cytokine staining and proliferation assays. IL-2-and IFN-␥-producing CD4 ϩ T cells were identified as either central or effector memory CD4 ϩ T cells using antibodies directed against CD45RO and the chemokine receptor CCR7. Control subjects mounted a memory T cell response comprising both central and effector memory CD4 ϩ T cells, with the central memory response occurring 1 wk before the effector memory response. IL-2 ϩ HBsAg-specific memory CD4 ϩ T cells were primarily detected within the effector population. Patients with ESRD showed a delayed response of IL-2-and IFN-␥-producing central memory CD4 ϩ T cells, but their maximal responses were similar to those of control subjects. In contrast, patients with ESRD produced only 6.3% of the IL-2 ϩ HBsAgspecific effector memory CD4 ϩ T cells produced by control subjects (0.5 Ϯ 0.2 ϫ 10 4 /L versus 8 Ϯ 3.5 ϫ 10 4 /L; P Ͻ 0.001), and this impaired response correlated with antigen-specific T cell proliferation and anti-HBsAg IgG titers. In conclusion, the production of antigen-specific effector memory CD4 ϩ T cells after vaccination, which is critical to achieve an adequate humoral response, is severely impaired in patients with ESRD. 19: 148319: -149019: , 200819: . doi: 10.1681 Patients with ESRD show clinical signs of an immune defect characterized by an increased susceptibility for infections and a decreased immune response to T cell-dependent antigens (e.g., hepatitis B vaccination). The precise mechanisms responsible for this immune defect are unknown; however, changes in T cell subsets and/or function may contribute substantially to the impaired cellular immune response, because ESRD is associated with lymphopenia occurring in the B and T lymphocyte compartment. [1][2][3] The available data on B cell function of patients with ESRD do not indicate an impaired function. 4 The functional data on peripheral T cells in patients with ESRD are conflicting and obtained by using the unfractionated bulk of circulating T cells. 1,3,5,6 Developments in T cell research and availability of various chemokine receptors, such as CCR7, have enabled a dissection of the T lymphocytes in different subsets. 7,8 The major T cell compartments that can be distinguished are the naive T cells (Tnaive; antigen inexperienced) and the antigen ex- J Am Soc Nephrol

Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients.Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Results Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. ConclusionsIn the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

Protocol © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Strength and limitations of this study ► The proposed scoping review will be the first paper to systematically search and map shared decisionmaking (SDM) interventions for treatment modality decisions in advanced kidney disease, evaluate the evidence on their reported outcomes and report on new developments or ongoing studies in this field. ► It will provide a comprehensive overview by collecting information from both quantitative and qualitative research, as well as the grey literature and key experts on SDM. ► Research in SDM is heterogeneous in its methodology and the reporting of outcomes; therefore a scoping review will be better suited to map, summarise and present this information than traditional systematic reviews or meta-analyses. ► Included studies will not undergo a formal quality assessment as scoping reviews attempt to provide an overview of all the existing evidence, regardless of its quality. ► Potentially relevant findings from papers written in other languages will be missed, as this study will only include papers written in English. AbStrACtIntroduction Patients with advanced kidney disease (AKD) have to make difficult treatment modality decisions as their disease progresses towards end-stage kidney disease. International guidelines in nephrology suggest shared decision-making (SDM) to help patients make timely treatment modality decisions that align with their values and preferences. However, systematic reviews or scoping reviews on these SDM interventions and on their reported use or outcomes are lacking. This limits the adoption of SDM in clinical practice and hampers further research and development on the subject. Our aim is to provide a comprehensive and up-to-date overview of these SDM interventions by means of a scoping review of the literature. Scoping reviews can provide a broad overview of a topic, identify gaps in the research knowledge base and report on the types of evidence that address and inform practices. This paper presents our study protocol. Methods and analysis The proposed scoping review will be performed in accordance with the Joanna Briggs Institute's (JBI) methodology for scoping reviews. It will cover both qualitative and quantitative scientific literature, as well as the grey literature on SDM interventions for treatment modality decisions in AKD. Only literature written in English will be considered for inclusion. Two independent reviewers will participate in an iterative process of screening the literature, paper selection and data extraction. Disagreements between the reviewers will be resolved by discussion until consensus is reached or after consultation with the research team when needed. Results will be reported with descriptive statistics and diagrammatic or tabular displayed information, accompanied by narrative summaries as explained in the JBI guidelines. Ethics and dissemination Ethical approval for the cond...

ObjectivesTo provide a comprehensive overview of interventions that support shared decision-making (SDM) for treatment modality decisions in advanced kidney disease (AKD). To provide summarised information on their content, use and reported results. To provide an overview of interventions currently under development or investigation.DesignThe JBI methodology for scoping reviews was followed. This review conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist.Data sourcesMEDLINE, Embase, Web of Science, Cochrane Library, Emcare, PsycINFO, PROSPERO and Academic Search Premier for peer-reviewed literature. Other online databases (eg, clinicaltrials.gov, OpenGrey) for grey literature.Eligibility for inclusionRecords in English with a study population of patients >18 years of age with an estimated glomerular filtration rate <30 mL/min/1.73 m2. Records had to be on the subject of SDM, or explicitly mention that the intervention reported on could be used to support SDM for treatment modality decisions in AKD.Data extraction and synthesisTwo reviewers independently screened and selected records for data extraction. Interventions were categorised as prognostic tools (PTs), educational programmes (EPs), patient decision aids (PtDAs) or multicomponent initiatives (MIs). Interventions were subsequently categorised based on the decisions they were developed to support.ResultsOne hundred forty-five interventions were identified in a total of 158 included records: 52 PTs, 51 EPs, 29 PtDAs and 13 MIs. Sixteen (n=16, 11%) were novel interventions currently under investigation. Forty-six (n=46, 35.7%) were reported to have been implemented in clinical practice. Sixty-seven (n=67, 51.9%) were evaluated for their effects on outcomes in the intended users.ConclusionThere is no conclusive evidence on which intervention is the most efficacious in supporting SDM for treatment modality decisions in AKD. There is a lot of variation in selected outcomes, and the body of evidence is largely based on observational research. In addition, the effects of these interventions on SDM are under-reported.

The finding that previous CVD was positively associated with eLVH may result from the permanent high cardiac output and the strong tendency for aortic valve calcification in this group of long-term hemodialysis patients, who suffer generally also from chronic anemia and various other metabolic derangements. No association was found between eLVH and parameters of fluid balance. The distribution of left ventricular geometry did not alter over time. The assumption that LV geometry worsens over time in susceptible individuals, who then suffer from a high risk of dying, may explain these findings.