34 research outputs found
sj-docx-1-cjk-10.1177_20543581221084499 – Supplemental material for Patient and Clinician Perspectives on the use of Remote Patient Monitoring in Peritoneal Dialysis
No full textSupplemental material, sj-docx-1-cjk-10.1177_20543581221084499 for Patient and Clinician Perspectives on the use of Remote Patient Monitoring in Peritoneal Dialysis by Benjamin Talbot, Sara Farnbach, Allison Tong, Steve Chadban, Shaundeep Sen, Vincent Garvey, Martin Gallagher and John Knight in Canadian Journal of Kidney Health and Disease</p
Circulating human progenitor cells - the sentinels of vascular repair?
No full textAbstract P.1.3Sarah L. Brice, Emma Thompson, Michaelia P. Cockshell, Shaundeep Sen, Claudine S. Bonde
Endothelial progenitor cells, uraemic toxins, and the development of endothelial dysfunction in chronic kidney disease.
No full textMorbidity and mortality rates for cardiovascular disease (CVD) are increased among end stage kidney disease (ESKD) patients receiving dialysis treatment, and not corrected with kidney transplantation (KTx). Classic CVD risk factors do not fully predict the increased risk, with novel factors causing endothelial dysfunction (ED), leading to arteriosclerosis, congestive heart failure (CHF) and sudden death, key to disease pathogenesis. These novel factors include bone marrow (BM) derived endothelial progenitor cells (EPCs), which have key roles in maintenance, repair and growth of the endothelium. There is limited data about the role of EPCs and CVD in the ESKD population. This uraemic milieu includes p-cresol (sulfate, PC/S) and indoxyl sulfate (IS), toxins associated with CVD in ESKD. In this thesis, the relationship between CVD and ESKD, and the potential role of EPCs and uraemic toxins was examined from epidemiological, clinical and laboratory perspectives. Data was obtained for the period between 2002-2007 for all hospital separations in Australia. Analysis was performed based on ICD-9/10 coding. This showed (for the first time in an Australian population): (i) an increase in risk for CVD hospital separations among dialysis and KTx, with higher rates for CHF than acute cardiac events (ACE); (ii) an advantage for KTx recipients in regards to ACE, but not CHF hospital separations, over dialysis recipients, and (iii) for CHF, no increase in in-hospital mortality, or length of stay per separation for any ESKD group compared to controls. At a clinical level, in groups of haemodialysis (HDx), KTx patients and controls, low peripheral blood (PB) EPC numbers were correlated with surrogate markers of CVD and ED. No clear relationship of IS and PC/S with ED was seen (although study power was limited). For in vitro studies, techniques were developed for isolation (Flow sort and AutoMACS), enumeration (FACS) and culture expansion of EPCs from BM and umbilical cord blood samples. The effects of uraemic serum and toxins PC and IS on cultured endothelial cells (ECs) and EPCs in vitro was examined, as a model of vascular pathology in ESKD. Greater HUVEC VCAM-1 expression and reduced tube formation in Matrigel were observed in response to increasing PC concentration than IS. The effect of IS (but not PC) at higher concentration in Matrigel was reduced by the addition of EPCs. Akt/ERK expression by western blot, cell migration to VEGF, and supernatant investigation by FlowCytoMix for soluble cell surface markers, were also performed. Testing of HUVEC function post-exposure to sera from control, transplant and HDx recipients did not replicate the above results on the basis of sera PC and IS levels. In summary, this thesis has explored the increased burden of CVD in ESKD patients in Australia, the relationship of EPCs, both in vivo and in vitro, to vascular disease in this setting, and the role of uraemic toxins as agents for CVD. These results underline why certain therapies may not be effective in the ESKD population for CVD prevention, and suggest novel approaches are needed.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201
Incorporation of endothelial progenitor cells into mosaic pseudoislets
No full textData source: Supplemental material, http://www.tandfonline.com/doi/suppl/10.4161/isl.3.3.15392?scroll=top
Link to a related website: https://www.tandfonline.com/doi/pdf/10.4161/isl.3.3.15392?needAccess=true, Open Access via UnpaywallPancreatic islet transplantation is limited by extensive apoptosis and suboptimal function of the implanted islets in the longer term. Endothelial progenitor cells (EPC) may be ideal for enhancing both the survival and function of transplanted islets. Here, we describe for the first time the in vitro formation of rat mosaic pseudoislets comprised of pancreatic β-cells with interspersed vasculogenic EPC. Bone marrow-derived EPC displayed a similar phenotype to non-adherent EPC, recently described in the human and mouse. Mosaic pseudoislet formation was enhanced by the use of an embryoid body forming medium (BPEL) and a spin protocol. Mosaic pseudoislets maintained function in vitro and may represent an enhanced cell therapy delivery approach to enhance the survival and revascularisation of transplanted islets.Daniella Penko, Daisy Mohanasundaram, Shaundeep Sen, Christopher Drogemuller, Claire Mee, Claudine S. Bonder, P. Toby H. Coates and Claire F. Jessu
Characterization of a distinct population of circulating human non-adherent endothelial forming cells and their recruitment via intercellular adhesion molecule-3
No full textCirculating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133+ population of non-adherent endothelial forming cells (naEFCs) which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38) together with mature endothelial cell markers (VEGFR2, CD144 and CD31). These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8)or myeloid markers (CD11b and CD14) which distinguishes them from ‘early’ endothelial progenitor cells (EPCs). Functional studies demonstrated that these naEFCs (i) bound Ulex europaeus lectin, (ii)demonstrated acetylated-low density lipoprotein uptake, (iii) increased vascular cell adhesion molecule (VCAM-1) surface expression in response to tumor necrosis factor and (iv) in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3- dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs). Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM)-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis.Sarah L. Appleby, Michaelia P. Cockshell, Jyotsna B. Pippal, Emma J. Thompson, Jeffrey M. Barrett, Katie Tooley, Shaundeep Sen, Wai Yan Sun, Randall Grose, Ian Nicholson, Vitalina Levina, Ira Cooke, Gert Talbo, Angel F. Lopez and Claudine S. Bonde
Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease
No full textLink to a related website: http://pdfs.semanticscholar.org/69e9/cf8474d787b5969b8e3304c392fcbc677864.pdf, Open Access via UnpaywallBone-marrow-derived EPCs (endothelial progenitor cells) play an integral role in the regulation and protection of the endothelium, as well as new vessel formation. Peripheral circulating EPC number and function are robust biomarkers of vascular risk for a multitude of diseases, particularly CVD (cardiovascular disease). Importantly, using EPCs as a biomarker is independent of both traditional and non-traditional risk factors (e.g. hypertension, hypercholesterolaemia and C-reactive protein), with infused ex vivo-expanded EPCs showing potential for improved endothelial function and either reducing the risk of events or enhancing recovery from ischaemia. However, as the number of existing cardiovascular risk factors is variable between patients, simple EPC counts do not adequately describe vascular disease risk in all clinical conditions and, as such, the risk of CVD remains. It is likely that this limitation is attributable to variation in the definition of EPCs, as well as a difference in the interaction between EPCs and other cells involved in vascular control such as pericytes, smooth muscle cells and macrophages. For EPCs to be used regularly in clinical practice, agreement on definitions of EPC subtypes is needed, and recognition that function of EPCs (rather than number) may be a better marker of vascular risk in certain CVD risk states. The present review focuses on the identification of measures to improve individual risk stratification and, further, to potentially individualize patient care to address specific EPC functional abnormalities. Herein, we describe that future therapeutic use of EPCs will probably rely on a combination of strategies, including optimization of the function of adjunct cell types to prime tissues for the effect of EPCs.Shaundeep Sen, Stephen P. McDonald, P. Toby H. Coates, and Claudine S. Bonde
Impact of supplemental private health insurance on dialysis and outcomes
No full textAIM:The influence of health insurance systems upon the treatment of end-stage kidney disease (ESKD) patients is poorly understood. We investigated how supplemental private health insurance (PHI) coverage impacted upon ESKD treatment modalities and patient outcomes. METHODS:All adult patients commencing ESKD treatment in New South Wales, Australia from 2000 to 2010 were identified using the Australia and New Zealand Dialysis and Transplant Registry. Data were linked to the state hospitalisation dataset to obtain insurance status, allowing the comparisons of mortality, ESKD treatment modality and health service utilisation between privately insured and public patients. RESULTS:The cohort of 5,737 patients included 38% (n=2,152) with PHI. At one-year after ESKD treatment initiation, PHI patients had lower mortality (HR 0.84, 95% CI 0.74-0.95, P=0.01), were more likely to be receiving home haemodialysis (OR 1.38, 95% CI 1.01-1.89, P=0.04), to have been transplanted (OR 1.75, 95% CI 1.25-2.46, P=0.001), and used fewer hospital days (IRR 0.85, 95% CI 0.74-0.96, P=0.01)After adjustment, PHI patients were more likely to initiate ESKD treatment with facility-based haemodialysis (OR 1.22, 95% CI 1.01-1.46, P=0.03), but were less likely to start on peritoneal dialysis (OR 0.81, 95% CI 0.67-0.98, P=0.03).. CONCLUSION:Our findings suggest that supplemental PHI in Australia is associated with lower risk ESKD treatment attributes and improved health outcomes. Greater understanding of the treatment pathways that deliver these outcomes may inform treatment for the broader ESKD treatment population. This article is protected by copyright. All rights reserved.Arunan Sriravindrarajah, Sradha S. Kotwal, Shaundeep Sen, Stephen McDonald, Meg Jardine, Alan Cass, Martin Gallaghe
Digital health interventions for physical activity in chronic kidney disease: Systematic review
No full textBackground Patients (pts) with rheumatoid arthritis (RA) often experience substantial pain despite treatment, and pain control is considered an important treatment outcome. The FINCH 1–3 studies demonstrated the efficacy and acceptable safety of the preferential Janus kinase (JAK) 1 inhibitor filgotinib (FIL) in pts living with RA.
Objectives This post-hoc analysis of the FINCH studies assessed specific effects of FIL on pain.
Methods FINCH 1–3 (NCT02889796, NCT02873936, NCT02886728) were Phase 3, randomized, double-blind trials of FIL 100 mg and 200 mg (FIL100/200). In FINCH 1, pts with an inadequate response (IR) to methotrexate (MTX) received FIL, adalimumab (ADA) or placebo (PBO) + MTX for 52 weeks. In FINCH 2, pts with an IR to biologic disease-modifying anti-rheumatic drugs (DMARDs) received FIL or PBO + conventional synthetic DMARDs for 24 weeks. In FINCH 3, MTX-naïve pts received FIL ± MTX or MTX for 52 weeks.
For each treatment group, pts reported pain on a 100-mm visual analog scale (VAS). Scores of ≤10 mm reflected limited to no pain; scores of ≤20 mm indicated health status was not negatively affected by pain.[1] Time to first VAS score of ≤10 mm was assessed. The proportion of pts who achieved remission (as per Disease Activity Score 28 with C-reactive protein [DAS28-CRP] <2.6 or Clinical Disease Activity Index [CDAI] ≤2.8) at Week 24 was evaluated. Of pts who achieved DAS28-CRP or CDAI remission, the proportion who also reported VAS pain scores of ≤10 mm or ≤20 mm was determined.
Results In FINCH 1, there was a higher probability of achieving a VAS pain score of ≤10 mm with FIL200, vs ADA + MTX or PBO + MTX; responses were better or comparable with FIL100 vs other treatment arms (Figure 1). Similar findings were observed in FINCH 2 and 3 for FIL vs PBO and MTX, respectively. In FINCH 1, the proportion of pts achieving DAS28-CRP remission was greater with FIL200 + MTX (48.4%) and comparable for the FIL100 + MTX (35.2%) vs ADA + MTX arms (35.7%; Table 1). Further, the proportion of pts who achieved VAS pain scores of ≤10 mm and ≤20 mm in addition to DAS28-CRP remission was 26.3% and 35.8%, respectively, in the FIL200 + MTX group, compared with 17.2% and 24.6% in the ADA + MTX group (Table 1). In FINCH 2 and 3, a greater proportion of pts in the FIL groups achieved remission vs the PBO or MTX arms, respectively. A greater proportion of pts achieved pain responses in addition to DAS28-CRP remission in the FIL groups of FINCH 2 and FINCH 3 compared with PBO or MTX, respectively. Findings were similar when CDAI remission was assessed.
Conclusion FIL positively affected pain parameters across the FINCH studies as early as Week 2, with responses sustained over time (up to Week 52 [FINCH 1 and 3] and Week 24 [FINCH 2]). In FINCH 1, FIL200 had a particularly favorable impact when pain response and remission were assessed together. Similar findings were seen with FIL compared with PBO and MTX in FINCH 2 and 3, respectively. These findings suggest that JAK inhibition may offer potential added value with respect to patient-reported pain outcomes when treat-to-target goals are met.
Reference [1] Taylor PC, et al. J Clin Med 2019;8:831No Full Tex
Acute interstitial nephritis and nephrogenic diabetes insipidus following treatment with sulfamethoxazole‐trimethoprim and temozolomide
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