Disparities in the completion of steps to kidney transplantation: protocol for a systematic review

Introduction Disparities in access to transplantation have been well documented. The extant literature, however, focuses largely on disparities and related barriers for African-American patients and none has used the steps to transplantation as a guiding framework. This review will catalogue disparities in the steps to transplantation as well as the barriers and facilitators to completion of each step identified in the extant literature. The results of the review will be used to generate recommendations for future research to improve equity in access to kidney transplantation. Methods and analysis Standard procedures will be used in the conduct of the review. Searches will be performed using the following electronic databases: PubMed/Medline, PsycINFO, CINHAL, EMBASE, Cochrane library and Web of Science. Reports of original research will be eligible for inclusion if they are published from 2005 to present, written or available in English language, performed in the USA, enrol adult participants (18 years of age or more), and employ descriptive or observational designs. Two authors will independently screen retrieved articles for inclusion. MaxQDA will be used for data analysis and management. All included reports will be coded for article characteristics; disparities identified; barriers and motivators of completion of steps to transplantation; and proposed solutions to disparities and barriers. Each report will be coded independently by two authors and discrepancies resolved by discussion among the full team. A qualitative approach to data analysis is planned. Risk of bias will be assessed using standard procedures. Ethics and dissemination The findings will provide crucial information on the current status of disparities in access to transplantation. PRISMA guidelines will be followed in reporting the results of the review. It is anticipated that these results will inform research which seeks to increase parity in access to transplantation. Systematic review registration PROSPERO CRD42014015027

Innate immunity of vascular smooth muscle cells contributes to two-wave inflammation in atherosclerosis, twin-peak inflammation in aortic aneurysms and trans-differentiation potential into 25 cell types

IntroductionVascular smooth muscle cells (VSMCs) are the predominant cell type in the medial layer of the aorta, which plays a critical role in aortic diseases. Innate immunity is the main driving force for cardiovascular diseases. MethodsTo determine the roles of innate immunity in VSMC and aortic pathologies, we performed transcriptome analyses on aortas from ApoE–/– angiotensin II (Ang II)-induced aortic aneurysm (AAA) time course, and ApoE–/– atherosclerosis time course, as well as VSMCs stimulated with danger-associated molecular patterns (DAMPs).ResultsWe made significant findings: 1) 95% and 45% of the upregulated innate immune pathways (UIIPs, based on data of 1226 innate immune genes) in ApoE–/– Ang II-induced AAA at 7 days were different from that of 14 and 28 days, respectively; and AAA showed twin peaks of UIIPs with a major peak at 7 days and a minor peak at 28 days; 2) all the UIIPs in ApoE–/– atherosclerosis at 6 weeks were different from that of 32 and 78 weeks (two waves); 3) analyses of additional 12 lists of innate immune-related genes with 1325 cytokine and chemokine genes, 2022 plasma membrane protein genes, 373 clusters of differentiation (CD) marker genes, 280 nuclear membrane protein genes, 1425 nucleoli protein genes, 6750 nucleoplasm protein genes, 1496 transcription factors (TFs) including 15 pioneer TFs, 164 histone modification enzymes, 102 oxidative cell death genes, 68 necrotic cell death genes, and 47 efferocytosis genes confirmed two-wave inflammation in atherosclerosis and twin-peak inflammation in AAA; 4) DAMPs-stimulated VSMCs were innate immune cells as judged by the upregulation of innate immune genes and genes from 12 additional lists; 5) DAMPs-stimulated VSMCs increased trans-differentiation potential by upregulating not only some of 82 markers of 7 VSMC-plastic cell types, including fibroblast, osteogenic, myofibroblast, macrophage, adipocyte, foam cell, and mesenchymal cell, but also 18 new cell types (out of 79 human cell types with 8065 cell markers); 6) analysis of gene deficient transcriptomes indicated that the antioxidant transcription factor NRF2 suppresses, however, the other five inflammatory transcription factors and master regulators, including AHR, NF-KB, NOX (ROS enzyme), PERK, and SET7 promote the upregulation of twelve lists of innate immune genes in atherosclerosis, AAA, and DAMP-stimulated VSMCs; and 7) both SET7 and trained tolerance-promoting metabolite itaconate contributed to twin-peak upregulation of cytokines in AAA. DiscussionOur findings have provided novel insights on the roles of innate immune responses and nuclear stresses in the development of AAA, atherosclerosis, and VSMC immunology and provided novel therapeutic targets for treating those significant cardiovascular and cerebrovascular diseases

Summarizing multiple networks based on their underlying clustering structure to guide joint clustering of hospitals admissions

Healthcare services planning and regulation involve finding patterns in hospitals admission to detect their needs in a timely manner. Admission patterns for certain diseases are more precise than a general pattern including all diseases. Towards the objective of clustering hospitals based on their monthly admission behavior for different diseases, this study investigates the similarity among multiple disease-specific hospital networks to guide a joint clustering of hospitals. In this paper, the disease super network is generated from health records data using graph matching instead of relying on biomedical literature that is used in the previous work. The health records-based disease network is constructed using more than 7 million discharge records that are extracted from the California State Inpatient Database between 2009 and 2011. Comparison of the disease network results obtained using health records of different years shows consistency in clustering structure despite temporal changes in admission data. We show that the joint clustering guided by the health records-based similarity improves clustering group homogeneity measures as compared to the clustering guided by literature-based similarity (average homogeneity 53% vs 41%, respectively). The code used to conduct this work is available at https://github.com/Nouf-Barakati/JointCLusteringofHospitals

Dobutamine-Induced Myoclonus in a Peritoneal Dialysis Patient: Case Report

Dobutamine is a weak beta-1 and a potent beta-2 adrenergic agonist commonly used to treat patients in cardiogenic shock. It enhances myocardial contractibility, increasing cardiac output. Myoclonus in patients receiving an infusion of dobutamine is rare and, although not fully understood, seems more common in patients with severe kidney failure. To our knowledge, this is the first reported case of dobutamine-induced myoclonus in a patient with kidney failure receiving peritoneal dialysis. Only 7% of the 518,749 patients of the United States requiring kidney replacement therapy receive peritoneal dialysis, with only a small unknown number of those with advanced heart failure manage with an infusion of inotropic medication. The low prevalence of combined advanced heart failure and kidney failure could partly explain this condition’s rarity. In this study, we report the case of a 64-year-old woman with kidney failure receiving peritoneal dialysis in whom myoclonus developed 3 weeks after starting a dobutamine infusion for advanced refractory heart failure. Infectious and other pharmacologic causes of myoclonus were ruled out. Initially, uremia was suspected; however, despite increasing her peritoneal dialysis dose, it was only after discontinuing the dobutamine infusion that her myoclonus resolved

Deterioration in renal function is associated with increased arterial stiffness

Background Higher levels of baseline pulse wave velocity (PWV) have been associated with longitudinal decline in renal function in patients with kidney disease. We examined longitudinal decline in renal function in relation to levels of PWV. We hypothesized that longitudinal decline in renal function in a community-based, nonclinic sample would be associated with higher levels of PWV. METHODS We conducted a 4-5 year longitudinal study with 482 community-living individuals free from acute stroke, dementia, and end-stage renal disease (mean age = 60.9 years; 59% women; 93.2% white; 10% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) = 79.2ml/min/1.73 m2). Multiple linear regression analyses were used to examine the association between changes in renal function (eGFR and serum creatinine) from baseline to follow-up and PWV levels at follow-up, the outcome measure. Regression coefficients were adjusted for age, sex, education, race/ethnicity, weight, activity level, mean arterial pressure, treatment of hypertension, and cardiovascular risk factors.RESULTS With adjustment for covariables, decline in renal function was associated with higher levels of PWV over a mean follow-up of 4.68 years.CONCLUSIONS Decline in renal functioning from baseline levels measured 4-5 years before measurement of PWV is related to higher levels of PWV in a community sample

sj-docx-1-pit-10.1177_15269248231164174 - Supplemental material for Testing the Differential Access Hypothesis That Black Kidney Transplant Candidates Perceive Social Network Access to Fewer Potential Living Donors Than White Candidates

Supplemental material, sj-docx-1-pit-10.1177_15269248231164174 for Testing the Differential Access Hypothesis That Black Kidney Transplant Candidates Perceive Social Network Access to Fewer Potential Living Donors Than White Candidates by Jonathan Daw, Mary Roberts, Avrum Gillespie, Ashton M. Verdery and Tanjala S. Purnell in Progress in Transplantation</p

sj-docx-3-pit-10.1177_15269248231164174 - Supplemental material for Testing the Differential Access Hypothesis That Black Kidney Transplant Candidates Perceive Social Network Access to Fewer Potential Living Donors Than White Candidates

Supplemental material, sj-docx-3-pit-10.1177_15269248231164174 for Testing the Differential Access Hypothesis That Black Kidney Transplant Candidates Perceive Social Network Access to Fewer Potential Living Donors Than White Candidates by Jonathan Daw, Mary Roberts, Avrum Gillespie, Ashton M. Verdery and Tanjala S. Purnell in Progress in Transplantation</p

sj-docx-2-pit-10.1177_15269248231164174 - Supplemental material for Testing the Differential Access Hypothesis That Black Kidney Transplant Candidates Perceive Social Network Access to Fewer Potential Living Donors Than White Candidates

Supplemental material, sj-docx-2-pit-10.1177_15269248231164174 for Testing the Differential Access Hypothesis That Black Kidney Transplant Candidates Perceive Social Network Access to Fewer Potential Living Donors Than White Candidates by Jonathan Daw, Mary Roberts, Avrum Gillespie, Ashton M. Verdery and Tanjala S. Purnell in Progress in Transplantation</p

Chronic Kidney Disease Transdifferentiates Veins into a Specialized Immune–Endocrine Organ with Increased MYCN-AP1 Signaling

Most patients with end-stage renal disease (ESRD) and advanced chronic kidney disease (CKD) choose hemodialysis as their treatment of choice. Thus, upper-extremity veins provide a functioning arteriovenous access to reduce dependence on central venous catheters. However, it is unknown whether CKD reprograms the transcriptome of veins and primes them for arteriovenous fistula (AVF) failure. To examine this, we performed transcriptomic analyses of bulk RNA sequencing data of veins isolated from 48 CKD patients and 20 non-CKD controls and made the following findings: (1) CKD converts veins into immune organs by upregulating 13 cytokine and chemokine genes, and over 50 canonical and noncanonical secretome genes; (2) CKD increases innate immune responses by upregulating 12 innate immune response genes and 18 cell membrane protein genes for increased intercellular communication, such as CX3CR1 chemokine signaling; (3) CKD upregulates five endoplasmic reticulum protein-coding genes and three mitochondrial genes, impairing mitochondrial bioenergetics and inducing immunometabolic reprogramming; (4) CKD reprograms fibrogenic processes in veins by upregulating 20 fibroblast genes and 6 fibrogenic factors, priming the vein for AVF failure; (5) CKD reprograms numerous cell death and survival programs; (6) CKD reprograms protein kinase signal transduction pathways and upregulates SRPK3 and CHKB; and (7) CKD reprograms vein transcriptomes and upregulates MYCN, AP1, and 11 other transcription factors for embryonic organ development, positive regulation of developmental growth, and muscle structure development in veins. These results provide novel insights on the roles of veins as immune endocrine organs and the effect of CKD in upregulating secretomes and driving immune and vascular cell differentiation