Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.

Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery.

Temporal changes in the utilization of kidneys from hepatitis C virus-infected donors in the United States.

Despite data demonstrating increased utilization of kidneys from hepatitis C virus (HCV)-infected donors, it is unknown whether this is due to an increase in the donor pool or improved organ utilization and whether data from early pilot trials were temporally associated with changes in organ utilization. We used data from the Organ Procurement and Transplantation Network on all kidney donors and recipients of kidney transplants from January 1, 2015, to March 31, 2022 to evaluate temporal changes using joinpoint regression. Our primary analyses compared donors on the basis of their HCV viremic status (HCV-infected vs HCV-negative). Kidney utilization changes were assessed by evaluating the kidney discard rate and kidneys transplanted per donor. A total of 81 833 kidney donors were included in the analysis. There was a statistically significant decrease in the discard rates of HCV-infected kidney donors from 40% to just over 20% over a 1-year period, with a concurrent increase in kidneys transplanted per donor. This increased utilization occurred in tandem with the publication of pilot trials involving HCV-infected kidney donors in HCV-negative recipients rather than an increase in the donor pool. Ongoing clinical trials may strengthen existing data, which could result in this practice becoming the accepted standard of care.

Benefit of B7-1 staining and abatacept for treatment-resistant post-transplant focal segmental glomerulosclerosis in a predominantly pediatric cohort: time for a reappraisal.

BACKGROUND: Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. METHODS: From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. RESULTS: Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8-56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07-3.9, p < 0.004). Two patients who were B7-1 negative on multiple KT biopsies did not respond to abatacept and lost graft function. One patient developed proteinuria while receiving belatacept, stained B7-1 positive, but did not respond to abatacept. CONCLUSIONS: Podocyte B7-1 staining in biopsies of KTRs with post-transplant FSGS identifies a subset of patients who may benefit from abatacept. A higher resolution version of the Graphical abstract is available as Supplementary information.

When is it safe to perform abdominal transplantation in patients with prior SARS-CoV-2 infection: A case series.

BACKGROUND: The Coronavirus disease 2019(COVID-19) pandemic has negatively impacted worldwide organ transplantation. However, there is limited information on recipients transplanted after SARS-CoV-2 infection. A full understanding of this scenario is required, as transplantation is a life-saving procedure and COVID-19 remains an ongoing threat. METHODS: Abdominal organ transplant recipients diagnosed with COVID-19 prior to transplantation were identified by chart review and clinical data were collected. The primary outcome was the transplant outcome including graft loss, rejection and death, and reactivation of infection post-transplant. RESULTS: We identified 14 patients who received abdominal organ transplants after symptomatic PCR confirmed SARS-CoV-2 infection; four patients had a positive PCR at the time of admission for transplantation. The median time of follow-up was 79 (22-190) days. One recipient with negative PCR before transplant tested positive 9 days after transplant. One of 14 transplanted patients developed disseminated mold infection and died 86 days after transplant. During the follow-up, only one patient developed rejection; thirteen patients had favorable graft outcomes. CONCLUSIONS: We were able to perform abdominal transplantation for patients with COVID-19 before transplant, even with positive PCR at the time of transplant. Larger studies are needed to determine the time to safe transplant after SARS-CoV-2 infection.

ETV2 (Ets Variant Transcription Factor 2)-Rhoj Cascade Regulates Endothelial Progenitor Cell Migration During Embryogenesis.

OBJECTIVE: Endothelial progenitors migrate early during embryogenesis to form the primary vascular plexus. The regulatory mechanisms that govern their migration are not completely defined. Here, we describe a novel role for ETV2 (Ets variant transcription factor 2) in cell migration and provide evidence for an ETV2-Rhoj network as a mechanism responsible for this process. Approach and Results: Analysis of RNAseq datasets showed robust enrichment of migratory/motility pathways following overexpression of ETV2 during mesodermal differentiation. We then analyzed ETV2 chromatin immunoprecipitation-seq and assay for transposase accessible chromatin-seq datasets, which showed enrichment of chromatin immunoprecipitation-seq peaks with increased chromatin accessibility in migratory genes following overexpression of ETV2. Migratory assays showed that overexpression of ETV2 enhanced cell migration in mouse embryonic stem cells, embryoid bodies, and mouse embryonic fibroblasts. Knockout of Etv2 led to migratory defects of Etv2-EYFP+ angioblasts to their predefined regions of developing embryos relative to wild-type controls at embryonic day (E) 8.5, supporting its role during migration. Mechanistically, we showed that ETV2 binds the promoter region of Rhoj serving as an upstream regulator of cell migration. Single-cell RNAseq analysis of Etv2-EYFP+ sorted cells revealed coexpression of Etv2 and Rhoj in endothelial progenitors at E7.75 and E8.25. Overexpression of ETV2 led to a robust increase in Rhoj in both embryoid bodies and mouse embryonic fibroblasts, whereas, its expression was abolished in the Etv2 knockout embryoid bodies. Finally, shRNA-mediated knockdown of Rhoj resulted in migration defects, which were partially rescued by overexpression of ETV2. CONCLUSIONS: These results define an ETV2-Rhoj cascade, which is important for the regulation of endothelial progenitor cell migration.

Treating hepatitis C virus in dialysis patients: How, when, and why?

The identification of hepatitis C virus (HCV) occurred in 1989, and soon thereafter, it was recognized that there was a higher prevalence of anti-HCV seropositivity in patients with end-stage renal disease (ESRD) when compared to the general population. Multiple extrahepatic manifestations have been associated with HCV infection in patients with ESRD; these include an increased prevalence and risk of cardiovascular complications, insulin resistance, diabetes mellitus, and lymphoproliferative disorders. Infection with HCV has also been associated with an increased relative risk of mortality in the ESRD patient when contrasted to those patients without infection. The availability of second-generation direct-acting antiviral agents has revolutionized the treatment of HCV in both the general population as well as those patients with advanced chronic kidney disease and receiving dialysis. These new treatment protocols are very well tolerated with limited side effects and manageable drug-drug interactions while achieving remarkable sustained viral response rates. It is important that nephrologists become familiar with the differing strategies available for HCV-infected ESRD patients so that the appropriate decision of when and who to treat can be made for each patient.

Thrombotic risk and features of patients with inferior vena cava agenesis: a multicentre, retrospective, observational study.

BACKGROUND: Inferior vena cava agenesis (IVCA) is a rare anomaly predisposing affected people to lower-limb venous thrombosis with low frequency of pulmonary embolism. Antenatal thrombosis and inherited thrombophilia have been suggested as causes of IVCA. However, there is little evidence on the clinical course and management of this condition. We designed a patient registry to assess the thrombotic risk and features of IVCA. METHODS: In this this multicentre, retrospective, observational study, we included patients with IVCA diagnosed by routine imaging from 20 hospitals in Spain (n=18), Portugal (n=1), and Italy (n=1). Patients were identified from a systematic search in radiology databases using data extraction software (cohort A) and alternative searches in medical records for confirmed IVCA (cohort B; option allowed when systematic approaches were unapplicable). Primary outcomes were clinical and imaging features, thrombotic risk, phenotype of IVCA-associated thrombosis, anticoagulant treatment, and the results of thrombophilia testing. FINDINGS: We included patients with IVCA diagnosed by routine imaging studies done between Jan 1, 2010, and Dec 31, 2022. In the systematic search, 4 341 333 imaging exams were screened from the radiology databases of eight centres. 122 eligible patients were enrolled in cohort A. A further 95 patients were identified by screening medical records at 12 centres, of whom 88 were eligible and included in cohort B, making a combined cohort of 210 patients. 96 (46%) of 210 patients were female and 200 (95%) were European or Hispanic. 60 (29%) of 210 patients had hepatic IVC interruption, whereas 150 (71%) had extrahepatic IVCA. In cohort A, 65 (53%) of 122 patients had venous thrombosis, with an estimated annual risk of 1·15% (95% CI 0·89-1·46). Extrahepatic IVCA was associated with a greater risk of venous thrombosis than hepatic IVCA (56 [67%] of 84 patients vs nine [24%] of 38 patients, odds ratio 5·31, 95% CI 2·27-12·43; p<0·0001). Analysis of 126 patients with venous thrombosis pooled from cohorts A and B showed early-onset (median age 34·6 years, IQR 23·3-54·3) and recurrent events (50 [40%] of 126 patients). Patients with extrahepatic IVCA had greater proportions of lower-limb venous thrombosis (95 [87%] of 109 vs nine [53%] of 17, p=0·0010) and recurrence (48 [44%] of 109 vs two [12%] of 17, p=0·015), but lower rates of pulmonary embolism (10 [10%] of 99 vs four [33%] of 12, p=0·044) than did patients with hepatic IVCA. 77 (63%) of 122 patients with thrombosis underwent indefinite anticoagulation. 32 (29%) of 111 patients (29 [34%] of 86 with thrombosis) had coexisting thrombophilias. The recurrence risk was lower for patients receiving indefinite anticoagulation (adjusted odds ratio 0·24, 95% CI 0·08-0·61; p=0·010), and greater for thrombophilias (3·19, 1·09-9·32; p=0·034). INTERPRETATION: This evaluation of a large patient cohort demonstrates the high thrombotic burden of IVCA. We have identified two distinct forms of IVCA, hepatic and extrahepatic, suggesting different underlying mechanisms. Beyond clinical characterisation, we draw attention to this orphan disease and highlight the need for its study and improved care. FUNDING: Spanish Society of Thrombosis and Haemostasis, Instituto de Salud Carlos III, FEDER, Fundación Séneca.

Impact of genetic structural variants in factor XI deficiency: identification, accurate characterization, and inferred mechanism by long-read sequencing.

BACKGROUND: Congenital factor XI (FXI) deficiency is a probably underestimated coagulopathy that confers antithrombotic protection. Characterization of genetic defects in F11 is mainly focused on the identification of single-nucleotide variants and small insertion/deletions because they represent up to 99% of the alterations accounting for factor deficiency, with only 3 gross gene defects of structural variants (SVs) having been described. OBJECTIVES: To identify and characterize the SVs affecting F11. METHODS: The study was performed in 93 unrelated subjects with FXI deficiency recruited in Spanish hospitals over a period of 25 years (1997-2022). F11 was analyzed by next-generation sequencing, multiplex ligand probe amplification, and long-read sequencing. RESULTS: Our study identified 30 different genetic variants. Interestingly, we found 3 SVs, all heterozygous: a complex duplication affecting exons 8 and 9, a tandem duplication of exon 14, and a large deletion affecting the whole gene. Nucleotide resolution obtained by long-read sequencing revealed Alu repetitive elements involved in all breakpoints. The large deletion was probably generated de novo in the paternal allele during gametogenesis, and despite affecting 30 additional genes, no syndromic features were described. CONCLUSION: SVs may account for a high proportion of F11 genetic defects implicated in the molecular pathology of congenital FXI deficiency. These SVs, likely caused by a nonallelic homologous recombination involving repetitive elements, are heterogeneous in both type and length and may be de novo. These data support the inclusion of methods to detect SVs in this disorder, with long-read-based methods being the most appropriate because they detect all SVs and achieve adequate nucleotide resolution.

FOXK1 regulates Wnt signalling to promote cardiogenesis.

AIMS: Congenital heart disease (CHD) is the most common genetic birth defect, which has considerable morbidity and mortality. We focused on deciphering key regulators that govern cardiac progenitors and cardiogenesis. FOXK1 is a forkhead/winged helix transcription factor known to regulate cell cycle kinetics and is restricted to mesodermal progenitors, somites, and heart. In the present study, we define an essential role for FOXK1 during cardiovascular development. METHODS AND RESULTS: We used the mouse embryoid body system to differentiate control and Foxk1 KO embryonic stem cells into mesodermal, cardiac progenitor cells and mature cardiac cells. Using flow cytometry, immunohistochemistry, cardiac beating, transcriptional and chromatin immunoprecipitation quantitative polymerase chain reaction assays, bulk RNA sequencing (RNAseq) and assay for transposase-accessible chromatin using sequencing (ATACseq) analyses, FOXK1 was observed to be an important regulator of cardiogenesis. Flow cytometry analyses revealed perturbed cardiogenesis in Foxk1 KO embryoid bodies (EBs). Bulk RNAseq analysis at two developmental stages showed a significant reduction of the cardiac molecular program in Foxk1 KO EBs compared to the control EBs. ATACseq analysis during EB differentiation demonstrated that the chromatin landscape nearby known important regulators of cardiogenesis was significantly relaxed in control EBs compared to Foxk1 KO EBs. Furthermore, we demonstrated that in the absence of FOXK1, cardiac differentiation was markedly impaired by assaying for cardiac Troponin T expression and cardiac contractility. We demonstrate that FOXK1 is an important regulator of cardiogenesis by repressing the Wnt/ß-catenin signalling pathway and thereby promoting differentiation. CONCLUSION: These results identify FOXK1 as an essential transcriptional and epigenetic regulator of cardiovascular development. Mechanistically, FOXK1 represses Wnt signalling to promote the development of cardiac progenitor cells.

The regulatory role of pioneer factors during cardiovascular lineage specification - A mini review.

Cardiovascular disease (CVD) remains the number one cause of death worldwide. Ischemic heart disease contributes to heart failure and has considerable morbidity and mortality. Therefore, alternative therapeutic strategies are urgently needed. One class of epigenetic regulators known as pioneer factors has emerged as an important tool for the development of regenerative therapies for the treatment of CVD. Pioneer factors bind closed chromatin and remodel it to drive lineage specification. Here, we review pioneer factors within the cardiovascular lineage, particularly during development and reprogramming and highlight the implications this field of research has for the future development of cardiac specific regenerative therapies.

ETV2 functions as a pioneer factor to regulate and reprogram the endothelial lineage.

The vasculature is an essential organ for the delivery of blood and oxygen to all tissues of the body and is thus relevant to the treatment of ischaemic diseases, injury-induced regeneration and solid tumour growth. Previously, we demonstrated that ETV2 is an essential transcription factor for the development of cardiac, endothelial and haematopoietic lineages. Here we report that ETV2 functions as a pioneer factor that relaxes closed chromatin and regulates endothelial development. By comparing engineered embryonic stem cell differentiation and reprogramming models with multi-omics techniques, we demonstrated that ETV2 was able to bind nucleosomal DNA and recruit BRG1. BRG1 recruitment remodelled chromatin around endothelial genes and helped to maintain an open configuration, resulting in increased H3K27ac deposition. Collectively, these results will serve as a platform for the development of therapeutic initiatives directed towards cardiovascular diseases and solid tumours.

Reciprocal changes in renal ACE/ANG II and ACE2/ANG 1-7 are associated with enhanced collecting duct renin in Goldblatt hypertensive rats.

Alterations in the balance between ANG II/ACE and ANG 1-7/ACE2 in ANG II-dependent hypertension could reduce the generation of ANG 1-7 and contribute further to increased intrarenal ANG II. Upregulation of collecting duct (CD) renin may lead to increased ANG II formation during ANG II-dependent hypertension, thus contributing to this imbalance. We measured ANG I, ANG II, and ANG 1-7 contents, angiotensin-converting enzyme (ACE) and ACE2 gene expression, and renin activity in the renal cortex and medulla in the clipped kidneys (CK) and nonclipped kidneys (NCK) of 2K1C rats. After 3 wk of unilateral renal clipping, systolic blood pressure and plasma renin activity increased in 2K1C rats (n = 11) compared with sham rats (n = 9). Renal medullary angiotensin peptide levels were increased in 2K1C rats [ANG I: (CK = 171 ± 4; NCK = 251 ± 8 vs. sham = 55 ± 3 pg/g protein; P < 0.05); ANG II: (CK = 558 ± 79; NCK = 328 ± 18 vs. sham = 94 ± 7 pg/g protein; P < 0.001)]; and ANG 1-7 levels decreased (CK = 18 ± 2; NCK = 19 ± 2 pg/g vs. sham = 63 ± 10 pg/g; P < 0.001). In renal medullas of both kidneys of 2K1C rats, ACE mRNA levels and activity increased but ACE2 decreased. In further studies, we compared renal ACE and ACE2 mRNA levels and their activities from chronic ANG II-infused (n = 6) and sham-operated rats (n = 5). Although the ACE mRNA levels did not differ between ANG II rats and sham rats, the ANG II rats exhibited greater ACE activity and reduced ACE2 mRNA levels and activity. Renal medullary renin activity was similar in the CK and NCK of 2K1C rats but higher compared with sham. Thus, the differential regulation of ACE and ACE2 along with the upregulation of CD renin in both the CK and NCK in 2K1C hypertensive rats indicates that they are independent of perfusion pressure and contribute to the altered content of intrarenal ANG II and ANG 1-7.

Angiotensin II Induces Differentiation of Human Neuroblastoma Cells by Increasing MAP2 and ROS Levels.

INTRODUCTION: The roles of angiotensin II (Ang II) in the brain are still under investigation. In this study, we investigated if Ang II influences differentiation of human neuroblastoma cells with simultaneous activation of NADPH oxidase and reactive oxygen species (ROS). Moreover, we investigated the Ang II receptor type involved during differentiation. METHODS: Human neuroblastoma cells (SH-SY5Y; 5 × 105 cells) were exposed to Ang II (600 nM) for 24 h. Differentiation was monitored by measuring MAP2 and NF-H levels. Cell size and ROS were analyzed by flow cytometry, and NADPH oxidase activation was assayed using apocynin (500 µM). Ang II receptors (ATR) activation was assayed using ATR blockers or Ang II metabolism inhibitors (10-7 M). RESULTS: (1) Cell size decreased significantly in Ang II-treated cells; (2) MAP2 and ROS increased significantly in Ang II-treated cells with no changes in viability; (3) MAP2 and ROS decreased significantly in cells incubated with Ang II plus apocynin. (4) A significant decrease in MAP2 was observed in cells exposed to Ang II plus PD123.319 (AT2R blocker). CONCLUSION: Our findings suggest that Ang II influences differentiation of SH-SY5Y by increasing MAP2 through the AT2R. The increase in MAP2 and ROS were also mediated through NADPH oxidase with no cell death.

Cytochrome c: Using Biological Insight toward Engineering an Optimized Anticancer Biodrug.

The heme protein cytochrome c (Cyt c) plays pivotal roles in cellular life and death processes. In the respiratory chain of mitochondria, it serves as an electron transfer protein, contributing to the proliferation of healthy cells. In the cell cytoplasm, it activates intrinsic apoptosis to terminate damaged cells. Insight into these mechanisms and the associated physicochemical properties and biomolecular interactions of Cyt c informs on the anticancer therapeutic potential of the protein, especially in its ability to subvert the current limitations of small molecule-based chemotherapy. In this review, we explore the development of Cyt c as an anticancer drug by identifying cancer types that would be receptive to the cytotoxicity of the protein and factors that can be finetuned to enhance its apoptotic potency. To this end, some information is obtained by characterizing known drugs that operate, in part, by triggering Cyt c induced apoptosis. The application of different smart drug delivery systems is surveyed to highlight important features for maintaining Cyt c stability and activity and improving its specificity for cancer cells and high drug payload release while recognizing the continuing limitations. This work serves to elucidate on the optimization of the strategies to translate Cyt c to the clinical market.

Release of Soluble Insulin Receptor From Neurons by Cerebrospinal Fluid From Patients With Neurocognitive Dysfunction and HIV Infection.

Previously, we found that high levels of soluble insulin receptor (sIR) in the cerebrospinal fluid (CSF) of an HIV-infected women cohort were associated with the presence and severity of HIV-associated neurocognitive disorders (HAND). In this study we investigated if CSF from this population, HIV-1 Tat, and selected cytokines induces sIR secretion from human neuronal cells. Twenty-three (23) HIV-seropositive women stratified by cognitive status and five HIV- seronegative women were evaluated. Soluble IR levels were measured in the extracellular medium of neuronal cells (SH-SY5Y) that were exposed (for 24 h) to the CSF of patients. The levels of sIR, HIV-1 Tat, and cytokine levels (IL-2, IL4, IL-6, IFNγ, TNFα, and IL-10) were quantified in the CSF of participants by ELISA and flow cytometry. Neuronal secretion of sIR was measured after exposure (24 h) to HIV-1 Tat (0.5-250 nM), or specific cytokines. The effects of TNFα and HIV-1 Tat on sIR secretion were also evaluated in the presence of R7050 (TNFα antagonist; 10 nM). Neurons exposed to the CSF of HIV-infected women had higher sIR levels according to the severity of neurocognitive impairment of the participant. Increased CSF sIR levels were associated with the presence and severity of HAND and were positively correlated with CSF HIV-1 Tat levels in HIV-infected women with cognitive impairment. CSF levels of IL-2, IFNγ, and TNFα were significantly increased with HAND. However, only TNFα (5 pg/mL) and HIV-1 Tat (100 nM) induced a significant increase in neuronal sIR secretion after 24 h exposure, an effect that was antagonized when each were combined with R7050. Our data suggests that TNFα and HIV-1 Tat from the CSF of HIV-infected women may regulate the secretion of sIR from neuronal cells and that the effect of HIV-1 Tat on sIR secretion may depend on TNFα receptor activation.

Etv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis.

Etv2, an Ets-transcription factor, governs the specification of the earliest hemato-endothelial progenitors during embryogenesis. While the transcriptional networks during hemato-endothelial development have been well described, the mechanistic details are incompletely defined. In the present study, we described a new role for Etv2 as a regulator of cellular proliferation via Yes1 in mesodermal lineages. Analysis of an Etv2-ChIPseq dataset revealed significant enrichment of Etv2 peaks in the upstream regions of cell cycle regulatory genes relative to non-cell cycle genes. Our bulk-RNAseq analysis using the doxycycline-inducible Etv2 ES/EB system showed increased levels of cell cycle genes including E2f4 and Ccne1 as early as 6 h following Etv2 induction. Further, EdU-incorporation studies demonstrated that the induction of Etv2 resulted in a ~2.5-fold increase in cellular proliferation, supporting a proliferative role for Etv2 during differentiation. Next, we identified Yes1 as the top-ranked candidate that was expressed in Etv2-EYFP+ cells at E7.75 and E8.25 using single cell RNA-seq analysis. Doxycycline-mediated induction of Etv2 led to an increase in Yes1 transcripts in a dose-dependent fashion. In contrast, the level of Yes1 was reduced in Etv2 null embryoid bodies. Using bioinformatics algorithms, biochemical, and molecular biology techniques, we show that Etv2 binds to the promoter region of Yes1 and functions as a direct upstream transcriptional regulator of Yes1 during embryogenesis. These studies enhance our understanding of the mechanisms whereby Etv2 governs mesodermal fate decisions early during embryogenesis.

Comparison of mortality of ESRD patients with lupus by initial dialysis modality.

BACKGROUND AND OBJECTIVES: Little is known regarding whether mortality among ESRD patients with SLE differs between those initiating with peritoneal dialysis (PD) versus hemodialysis (HD). This study compared the mortality risk of ESRD patients with SLE initiating with PD versus HD after matching their baseline sociodemographic and clinical factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Of 11,023 ESRD patients with SLE initiating dialysis with PD or HD between 1995 and 2006 with complete records in the US Renal Data System, 1352 pairs were matched on 13 predictors utilizing a predicted probability of group membership into the PD group using propensity score matching. The primary outcome was overall mortality. Secondary outcomes were cardiovascular-related and infection-related mortality. Outcomes were compared between groups with survival statistics. The period of observation ended on December 31, 2009. The median follow-up was 3 years. RESULTS: Matched pairs were predominantly women (86%) with a median age of 39 years. Matched pairs had a balance (P ≥ 0.05) of all baseline factors. Matched pairs had a similar risk of overall mortality (hazard ratio, 0.96 [95% confidence interval, 0.82 to 1.13]; mortality, 21.4% [290 to 1352] versus 22.5% [304 to 1352] for PD versus HD) within the first 3 years of observation. Matched pairs also had similar cardiovascular-related mortality (10.5% versus 9.5% for PD versus HD) and infection-related mortality (3% versus 4.4% for PD versus HD). CONCLUSIONS: In ESRD patients with SLE, the mortality was similar among those initiating with PD versus HD after predictors were matched between groups.