Implementing a Health Utility Assessment Platform to Acquire Health Utilities in a Hemodialysis Outpatient Setting: Feasibility Study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) wait roughly 4 years for a kidney transplant. A potential way to reduce wait times is using hepatitis C virus (HCV)-viremic kidneys. OBJECTIVE: As preparation for developing a shared decision-making tool to assist patients with ESKD with the decision to accept an HCV-viremic kidney transplant, our initial goal was to assess the feasibility of using The Gambler II, a health utility assessment tool, in an ambulatory dialysis clinic setting. Our secondary goals were to collect health utilities for patients with ESKD and to explore whether the use of race-matched versus race-mismatched exemplars impacted the knowledge gained during the assessment process. METHODS: We used The Gambler II to elicit utilities for the following ESKD-related health states: hemodialysis, kidney transplant with HCV-unexposed kidney, and transplantation with HCV-viremic kidney. We created race exemplar video clips describing these health states and randomly assigned patients into the race-matched or race-mismatched video arms. We obtained utilities for these 3 health states from each patient, and we evaluated knowledge about ESKD and HCV-associated health conditions with pre- and postintervention knowledge assessments. RESULTS: A total of 63 patients with hemodialysis from 4 outpatient Dialysis Center Inc sites completed the study. Mean adjusted standard gamble utilities for hemodialysis, transplant with HCV-unexposed kidney, and transplantation with HCV-viremic kidney were 82.5, 89, and 75.5, respectively. General group knowledge assessment scores improved by 10 points (P<.05) following utility assessment process. The use of race-matched exemplars had little effect on the results of the knowledge assessment of patients. CONCLUSIONS: Using The Gambler II to collect utilities for patients with ESKD in an ambulatory dialysis clinic setting proved feasible. In addition, educational information about health states provided as part of the utility assessment process tool improved patients' knowledge and understanding about ESKD-related health states and implications of organ transplantation with HCV-viremic kidneys. A wide variation in patient health state utilities reinforces the importance of incorporating patients' preferences into decisions regarding use of HCV-viremic kidneys for transplantation.

Targeted knockdown of Kv1.3 channels in T lymphocytes corrects the disease manifestations associated with systemic lupus erythematosus.

Lupus nephritis (LN) is an autoimmune disease with substantial morbidity/mortality and limited efficacy of available therapies. Memory T (Tm) lymphocytes infiltrate LN kidneys, contributing to organ damage. Analysis of LN, diabetic nephropathy, and healthy donor kidney biopsies revealed high infiltration of active CD8+ Tm cells expressing high voltage-dependent Kv1.3 potassium channels-key T cell function regulators-in LN. Nanoparticles that selectively down-regulate Kv1.3 in Tm cells (Kv1.3-NPs) reduced CD40L and interferon-γ (IFNγ) in Tm cells from LN patients in vitro. Kv1.3-NPs were tested in humanized LN mice obtained by engrafting peripheral blood mononuclear cells (PBMCs) from LN patients into immune-deficient mice. LN mice exhibited features of the disease: increased IFNγ and CD3+CD8+ T cell renal infiltration, and reduced survival versus healthy donor PBMC engrafted mice. Kv1.3-NP treatment of patient PBMCs before engraftment decreased CD40L/IFNγ and prolonged survival of LN mice. These data show the potential benefits of targeting Kv1.3 in LN.

External beam radiation therapy for PTFE dialysis grafts: a pilot study.

PURPOSE: The aim of this study was to identify the effects of external beam radiation on PTFE dialysis graft dysfunction. METHODS: Seven patients who underwent PTFE dialysis graft angioplasty were randomized to receive either two 8 Gy doses of external beam radiation or no radiation. The primary endpoint was time to graft thrombosis with a secondary endpoint of time to first intervention. RESULTS: There was no statistically significant difference between the two groups in either of the endpoints, although grafts in the radiation group had a shorter time to thrombosis or intervention. CONCLUSIONS: Our results demonstrate technical feasibility for use of external beam radiation in the setting of dialysis vascular access graft dysfunction. Larger randomized studies are required to identify whether there is a clinical benefit from this intervention.

Differential calcium signaling and Kv1.3 trafficking to the immunological synapse in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) T cells exhibit several activation signaling anomalies including defective Ca(2+) response and increased NF-AT nuclear translocation. The duration of the Ca(2+) signal is critical in the activation of specific transcription factors and a sustained Ca(2+) response activates NF-AT. Yet, the distribution of Ca(2+) responses in SLE T cells is not known. Furthermore, the mechanisms responsible for Ca(2+) alterations are not fully understood. Kv1.3 channels control Ca(2+) homeostasis in T cells. We reported a defect in Kv1.3 trafficking to the immunological synapse (IS) of SLE T cells that might contribute to the Ca(2+) defect. The present study compares single T cell quantitative Ca(2+) responses upon formation of the IS in SLE, normal, and rheumatoid arthritis (RA) donors. Also, we correlated cytosolic Ca(2+) concentrations and Kv1.3 trafficking in the IS by two-photon microscopy. We found that sustained [Ca(2+)](i) elevations constitute the predominant response to antigen stimulation of SLE T cells. This defect is selective to SLE as it was not observed in RA T cells. Further, we observed that in normal T cells termination of Ca(2+) influx is accompanied by Kv1.3 permanence in the IS, while Kv1.3 premature exit from the IS correlates with sustained Ca(2+) responses in SLE T cells. Thus, we propose that Kv1.3 trafficking abnormalities contribute to the altered distribution in Ca(2+) signaling in SLE T cells. Overall these defects may explain in part the T cell hyperactivity and dysfunction documented in SLE patients.

Altered dynamics of Kv1.3 channel compartmentalization in the immunological synapse in systemic lupus erythematosus.

Aberrant T cell responses during T cell activation and immunological synapse (IS) formation have been described in systemic lupus erythematosus (SLE). Kv1.3 potassium channels are expressed in T cells where they compartmentalize at the IS and play a key role in T cell activation by modulating Ca(2+) influx. Although Kv1.3 channels have such an important role in T cell function, their potential involvement in the etiology and progression of SLE remains unknown. This study compares the K channel phenotype and the dynamics of Kv1.3 compartmentalization in the IS of normal and SLE human T cells. IS formation was induced by 1-30 min exposure to either anti-CD3/CD28 Ab-coated beads or EBV-infected B cells. We found that although the level of Kv1.3 channel expression and their activity in SLE T cells is similar to normal resting T cells, the kinetics of Kv1.3 compartmentalization in the IS are markedly different. In healthy resting T cells, Kv1.3 channels are progressively recruited and maintained in the IS for at least 30 min from synapse formation. In contrast, SLE, but not rheumatoid arthritis, T cells show faster kinetics with maximum Kv1.3 recruitment at 1 min and movement out of the IS by 15 min after activation. These kinetics resemble preactivated healthy T cells, but the K channel phenotype of SLE T cells is identical to resting T cells, where Kv1.3 constitutes the dominant K conductance. The defective temporal and spatial Kv1.3 distribution that we observed may contribute to the abnormal functions of SLE T cells.

Alternative medicine use in dialysis patients: potential for good and bad!

Although alternative medicines are widely used within the general population, the extent of their use within the dialysis population is unknown. It is possible that dialysis patients may be more likely to turn towards alternative therapies in view of the chronicity of their disease. In addition, this particular patient population could be at an increased risk of toxicity from these therapies due to an absence of renal excretion. A detailed assessment of complementary and alternative medicine use in our dialysis patients revealed that 18% of our patients had used or were using some form of alternative medicine therapy. An additional 63% of our patients, however, were willing to use a complementary or alternative medication. Our results suggest that hemodialysis patients are extremely receptive to the use of such therapies and are therefore exposed to all their potential benefit and harm.

Role of C-reactive protein, reticulocyte haemoglobin content and inflammatory markers in iron and erythropoietin administration in dialysis patients.

AIM: C-reactive protein (CRP) is an acute phase reactant protein, which becomes elevated in response to inflammation, infections or malignancies. These conditions are well known causes of bone marrow hyporesponsiveness and erythropoietin resistance in dialysis patients. The role of iron-deficiency as a cause of hyporesponsiveness under these conditions is not clear. Reticulocyte haemoglobin content (CHr) is one of several iron indices used to determine iron deficiency in dialysis patients. The aim of this study is to evaluate the role of CRP and CHr in iron administration and anaemia management in dialysis patients. METHODS: In 47 haemodialysis patients with ferritin levels of >500 ng/mL, CRP, CHr, transferrin saturation (TSAT), other markers and erythropoietin dose were evaluated. Patients with CRP < 5 mg/L (Group A) were compared to patients with CRP > 5 mg/L (Group B). RESULTS: Ferritin levels in the two groups were not different. Weekly erythropoietin was significantly different between the two groups. Group B required an average of 121% more erythropoietin than Group A to maintain similar haemoglobin levels of 11-12 g/dL 36% of Group B had CHr < 29 pg versus 7% of patients in Group A. 39% of patients in Group B also had TSAT < 20% versus 0% in Group A. Group A also had more arteriovenous (AV) fistulae as dialysis access than group B. CONCLUSION: Data indicate that low CHr, similar to low TSAT, could be associated with inflammatory process and erythropoietin resistance, but not necessarily with iron-deficiency. High CRP association with low CHr and low TSAT levels can explain the lack of response to further IV iron therapy. AV grafts, contrary to AV fistulae, are associated with high inflammatory markers and also with a higher erythropoietin requirement.