Effect of F11 Receptor/Junctional Adhesion Molecule-A-derived Peptide on Neointimal Hyperplasia in a Murine Model.

PURPOSE: To determine whether inhibition of the F11 receptor/JAM-A (F11R) using F11R-specific antagonist peptide 4D results in inhibition of smooth muscle cell (SMC) proliferation and migration in vivo, known as neointimal hyperplasia (NIH), using a mouse focal carotid artery stenosis model (FCASM). MATERIALS AND METHODS: The mouse FCASM was chosen to test the hypothesis because the dominant cell type at the site of stenosis is SMC, similar to that in vascular access stenosis. Fourteen C57BL/6 mice underwent left carotid artery (LCA) partial ligation to induce stenosis, followed by daily injection of peptide 4D in 7 mice and saline in the remaining 7 mice, and these mice were observed for 21 days and then euthanized. Bilateral carotid arteries were excised for histologic analysis of the intima and media areas. RESULTS: The mean intimal area was significantly larger in control mice compared with peptide 4D-treated mice (0.031 mm2 [SD ± 0.024] vs 0.0082 mm2 [SD ± 0.0103]; P = .011). The mean intima-to-intima + media area ratio was significantly larger in control mice compared with peptide 4D-treated mice (0.27 [SD ± 0.13] vs 0.089 [SD ± 0.081]; P = .0079). NIH was not observed in the right carotid arteries in both groups. CONCLUSIONS: Peptide 4D, an F11R antagonist, significantly inhibited NIH in C57BL/6 mice in a FCASM.

Triple negative breast cancer metastasis is hindered by a peptide antagonist of F11R/JAM­A protein.

BACKGROUND: The F11R/JAM-A cell adhesion protein was examined as the therapeutic target in triple negative breast cancer (TNBC) with the use of the peptide antagonist to F11R/JAM-A, that previously inhibited the early stages of breast cancer metastasis in vitro. METHODS: The online in silico analysis was performed by TNMPlot, UALCAN, and KM plotter. The in vitro experiments were performed to verify the effect of peptide 4D (P4D) on human endothelial cell lines EA.hy926 and HMEC-1 as well as on human TNBC cell line MDA-MB-231. The cell morphology upon P4D treatment was verified by light microscopy, while the cell functions were assessed by colony forming assay, MTT cell viability assay, BrdU cell proliferation assay, and Transepithelial/Endothelial Electrical Resistance measurements. The in vivo experiments on 4T1 murine breast cancer model were followed by histopathological analysis and a series of quantitative analyses of murine tissues. RESULTS: By in silico analysis we have found the elevated gene expression in breast cancer with particular emphasis on TNBC. The elevated F11R expression in TNBC was related with poorer survival prognosis. Peptide 4D has altered the morphology and increased the permeability of endothelial monolayers. The colony formation, viability, and proliferation of MDA-MB-231 cells were decreased. P4D inhibited the metastasis in 4T1 breast cancer murine model in a statistically significant manner that was demonstrated by the resampling bootstrap technique. CONCLUSIONS: The P4D peptide antagonist to F11R/JAM-A is able to hinder the metastasis in TNBC. This assumption needs to be confirmed by additional 4T1 mouse model study performed on larger group size, before making the decision on human clinical trials.

Anti-N-methyl-d-aspartate Receptor Encephalitis Related Sinus Node Dysfunction and the Lock-Step Phenomenon.

Described in 2007, anti-N-methyl-d-aspartate receptor encephalitis (ANMDARE) is a rare autoimmune limbic encephalitis affecting young adults (predominantly women of reproductive age) and is a paraneoplastic manifestation of ovarian teratoma in about half of the cases. ANMDARE is characterized by psychiatric changes, neurological changes, autonomic instability and cardiac dysrhythmias. In this report, we present a 36-year-old woman who was 16 weeks pregnant and brought to the hospital with confusion and subsequently had a seizure with Electroencephalography (EEG) demonstrated an extreme delta brush pattern consistent with ANMDARE. Patient developed sinus nodal dysfunction and was also found to have ovarian teratoma, a rather typical presentation for ANMDARE, that is considered a paraneoplastic syndrome for ovarian teratoma. In this report, we highlight the cardiac manifestation of ANMDARE, the pathophysiology associated with autonomic instability, and management strategies of this rare, and largely devastating illness.

Functional inhibition of F11 receptor (F11R/junctional adhesion molecule-A/JAM-A) activity by a F11R-derived peptide in breast cancer and its microenvironment.

PURPOSE: To examine the involvement of the F11R/JAM-A protein in breast cancer metastasis, we utilized the F11R/JAM-A antagonistic peptide 4D (P4D) in experiments of transendothelial migration (TEM) of breast cancer cells. METHODS: Experiments were conducted in the mouse 4T1 breast cancer model utilizing the human mammary epithelial cell and endothelial cell lines. The levels of soluble F11R/JAM-A (sJAM-A) in the murine plasmas were measured by ELISA. Levels of F11R/JAM-A mRNA and protein in cell lines were assessed by qRT-PCR and Western blot, respectively. Cell surface expression of F11R/JAM-A was demonstrated by flow cytometry. Functional tests included the TEM of breast cancer cells and adhesion of breast cancer cells to the endothelium. The endothelial permeability was studied by fluorescent tracer assay and by the Real-Time Cell Analysis (RTCA). RESULTS: The tumor inducers Tß4 and TGF-ß1 reduced the levels of sJAM-A in murine plasma, and reduced the F11R/JAM-A protein levels in the human microvascular endothelial cell line HMEC-1. The adhesion and TEM measured between breast cancer cells and inflamed or Tß4-treated endothelium were inhibited by P4D. The presence of P4D did not destabilize the pre-existing tight junctions in the endothelial monolayer. The barrier-protecting effect of P4D was stronger than that of forskolin, when a booster dose of P4D was applied to the inflamed endothelium. CONCLUSIONS: F11R/JAM-A protein can be considered as a novel target in the treatment of breast cancer metastasis. In vivo and clinical studies are needed to further investigate the effectiveness of F11R/JAM-A-derived peptide as a possible anti-metastatic drug.

A peptide antagonist of F11R/JAM-A reduces plaque formation and prolongs survival in an animal model of atherosclerosis.

BACKGROUND AND AIMS: The F11 Receptor (F11R), AKA Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A), is an adhesion protein constitutively expressed on the membrane surface of circulating platelets and the luminal surface of inflamed endothelial cells (EC). Platelet adhesion to an inflamed endothelium is one of the early steps of atherosclerotic plaque formation. Our previous studies, conducted with cultured EC in vitro, have demonstrated the expression of F11R/JAM-A on the luminal surface of inflamed EC, platelet adhesion to inflamed EC through F11R/JAM-A interactions, and inhibition of this interaction by the presence of F11R/JAM-A antagonistic peptide (F11Rpeptide 4D). In the present study, we examined in vivo the overall health-benefits and cardiovascular effects of long-term treatment of animals prone to atherosclerosis, ApoE-/- mice, with F11R-peptide 4D. METHODS: Twenty ApoE-/- mice were assigned to daily treatment with peptide 4D and compared to their counterparts control untreated mice. Mice were observed for wellness and survival. Plaque size in the aorta and heart was measured using histological analysis. Effects of peptide 4D (or scramble control) on platelet adhesion to inflamed endothelium were measured using intravital microscopy. RESULTS: Significant reductions in atherosclerotic plaques number and size, an overall robust health with longer survival were found in the peptide 4D treated group of ApoE-/- mice. Intravital microscopic studies conducted in exposed vessels of ApoE-/- mice demonstrated significant inhibition by peptide 4D of platelet adhesion to the cytokine-inflamed endothelium. CONCLUSIONS: Our results demonstrate that peptide 4D significantly reduces atherosclerotic plaque formation in ApoE-/- mice and inhibits platelet adhesion to the inflamed arterial endothelium.

Trends and outcomes in dual kidney transplantation- A narrative review.

Dual kidney transplantation (DKT) is a viable option to increase the donor pool and improve access equity to kidney transplantation. Dual kidneys are procured from carefully selected marginal donors that are not generally acceptable to most transplant centers. This is a narrative review of literature focusing on donor kidney allocation systems and selection of the ideal recipient for DKT. We also discussed surgical approaches for DKTs as well as patient and allograft outcomes. We found that most studies to date showed that DKTs has similar graft survival and delayed graft function rates when compared to single kidney transplants (SKTs). DKT is technically feasible with outcomes that are comparable to expanded criteria donor kidneys (ECD); and has substantial potential in expanding the donor pool. For allograft survival, most studies with strict allocation criteria showed that graft survival was similar in DKT as compared to SKT - ECD transplants.. Our review may encourage transplant centers to review their policies for donor and recipient selection leading to increase in DKT.

Mortality after Renal Allograft Failure and Return to Dialysis.

INTRODUCTION: The outcomes of patients who fail their kidney transplant and return to dialysis (RTD) has not been investigated in a nationally representative sample. We hypothesized that variations in management of transplant chronic kidney disease stage 5 leading to kidney allograft failure (KAF) and RTD, such as access, nutrition, timing of dialysis, and anemia management predict long-term survival. METHODS: We used an incident cohort of patients from the United States Renal Data System who initiated hemodialysis between January 1, 2003 and December 31, 2008, after KAF. We used Cox regression analysis for statistical associations, with mortality as the primary outcome. RESULTS: We identified 5,077 RTD patients and followed them for a mean of 30.9 ± 22.6 months. Adjusting for all possible confounders at the time of RTD, the adjusted hazards ratio (AHR) for death was increased with lack of arteriovenous fistula at initiation of dialysis (AHR 1.22, 95% CI 1.02-1.46, p = 0.03), albumin <3.5 g/dL (AHR 1.33, 95% CI 1.18-1.49, p = 0.0001), and being underweight (AHR 1.30, 95% CI 1.07-1.58, p = 0.006). Hemoglobin <10 g/dL (AHR 0.96, 95% CI 0.86-1.06, p = 0.46), type of insurance, and zip code-based median household income were not associated with higher mortality. Glomerular filtration rate <10 mL/min/1.73 m2 at time of dialysis initiation (AHR 0.83, 95% CI 0.75-0.93, p = 0.001) was associated with reduction in mortality. CONCLUSIONS: Excess mortality risk observed in patients starting dialysis after KAF is multifactorial, including nutritional issues and vascular access. Adequate preparation of patients with failing kidney transplants prior to resuming dialysis may improve outcomes.

Clinical Characteristics and Angiographic Findings of Acute Myocardial Infarction Associated With Marijuana Use: Consecutive Case Series.

BACKGROUND: Marijuana use has been increasingly legalized in the United States resulting in substantial rise in the number of users especially in the younger populations. While our group and others had described various metabolic effects of this drug, little is known about its association with acute myocardial infarction. OBJECTIVE: To present a series of 8 patients with 10 events of ST-elevation MI (STEMI) associated with marijuana use; highlighting their demographic, clinical presentation, laboratory results and angiographic characteristics. METHODS: Retrospective chart review of patients with STEMI presenting to our inner city hospital Coronary Care Unit over a period of 4 years (December 2013-April 2017). RESULTS: Of the 10 case subjects studied who presented with chest pain, EKG evidence of STEMI with cannabis use, mean age at presentation was 40.1 ± 9.7 (years) SD, ranging from 26 to 59 years old. There were 9 males and one female, of them, 8 were Black, 2 Hispanic and 1 White. Of the 10 cases, 3 (30%) had no known cardiovascular disease (CVD) risk factors (RF) on admission, 1 patient had 3 RF, 4 patients had 2 RF and 2 had 1 CVD RF, which included age, diabetes mellitus type 2 (DM2), hypertension, dyslipidemia, smoking, and family history of premature coronary heart disease. Troponin I (cTnI) peak mean level was 93.5 ± 34.35 ng/ml, range 7.86 - 358.0 ng/ml. All patients had angiographic evidence of obstructive coronary angiography. CONCLUSION: In our study, marijuana use is associated with ST-elevation MI in largely minority population, occurring at a relatively younger age with half of the cases either low risk or CVD risk free. Additional studies are needed to further characterize this population given the increase in marijuana use.

Survival benefits in colorectal adenocarcinoma with the use of metformin among a black diabetic inner city population.

We assessed the association of metformin use with survival in colorectal cancer in a population consists mostly of African-American and Afro-Caribbean patients. We identified 585 colorectal cancer patients, 167 (28.6%) and 418 (71.5%) were as diabetic (DM) and nondiabetic, respectively. The diagnosis of diabetes did not impact cancer survival or extent of disease. Overall, DMs with metformin use (D+M+) have better overall survival than both DMs without metformin use (D+M∼) and nondiabetics (D∼M∼), with a mean survival of 109.9 months compared with 95.7 and 106.1 months, respectively (log-rank p < 0.05). The use of metformin shows significant reduction of risk of mortality compared with nonusers (hazard ratio: 0.34; 95% CI: 0.15-0.81; p = 0.01). Use of insulin and status of diabetes did not have a significant impact on overall cancer survival.

Standardised incidence ratios (SIRs) for cancer after renal transplant in systemic lupus erythematosus (SLE) and non-SLE recipients.

OBJECTIVE: We investigated malignancy risk after renal transplantation in patients with and without systemic lupus erythematosus (SLE). METHODS: Using the United States Renal Data System from 2001 to 2009, 143 652 renal transplant recipients with and without SLE contributed 585 420 patient-years of follow-up to determine incident cancers using Medicare claims codes. We calculated standardised incidence ratios (SIRs) of cancer by group using age, sex, race/ethnicity-specific and calendar year-specific cancer rates compared with the US population. RESULTS: 10 160 cancers occurred at least 3 months after renal transplant. Overall cancer risk was increased in both SLE and non-SLE groups compared with the US general population, SIR 3.5 (95% CI 2.1 to 5.7) and SIR 3.7 (95% CI 2.4 to 5.7), respectively. Lip/oropharyngeal, Kaposi, neuroendocrine, thyroid, renal, cervical, lymphoma, liver, colorectal and breast cancers were increased in both groups, whereas only melanoma was increased in SLE and lung cancer was increased in non-SLE. In Cox regression analysis, SLE status (HR 1.1, 95% CI 0.9 to 1.3) was not associated with increased risk of developing cancer, adjusted for other independent risk factors for developing cancer in renal transplant recipients. We found that smoking (HR 2.2, 95% CI 1.2 to 4.0), cytomegalovirus positivity at time of transplant (HR 1.3, 95% CI 1.2 to 1.4), white race (HR 1.2, 95% CI 1.2 to 1.3) and older recipient age at time of transplantation (HR 1.0 95% CI 1.0 to 1.2) were associated with an increased risk for development of cancer, whereas shorter time on dialysis, Epstein-Barr virus or HIV were associated with a lower risk for development of cancer. CONCLUSIONS: Cancer risk in renal transplant recipients appeared similar in SLE and non-SLE subjects, aside from melanoma. Renal transplant recipients may need targeted counselling regarding surveillance and modifiable risk factors.

Impact of renal posttransplantation amputation on allograft outcomes: a study of United States renal data system.

BACKGROUND: The prevalence of renal posttransplantation amputation and its impact on allograft and patient survival have not been widely reported. METHODS: We used an incident cohort of patients who underwent renal transplantation between June 2004 and September 2009. Amputation data were obtained using Medicare institutional claim forms. Baseline demographics and comorbidities, such as peripheral vascular disease (PVD), diabetes, ischemic heart disease, cerebrovascular disease, hypertension, and smoking, were captured. The chi-square and t tests were used for statistical associations. Kaplan-Meier survival curves were plotted for renal allograft and patient survival. Independent associations between patient factors and amputation were examined using multivariable Cox regression analysis. RESULTS: Of the 85,873 renal transplant recipients, 1062 patients had amputation. The prevalence of amputation was higher in those with PVD versus those without PVD at listing (5.6% vs. 1%; P=0.0001). Mean allograft survival was 55.5±0.55 months in patients with amputation versus 60.6±0.06 months in patients without amputation (P=0.0001). All-cause mortality was higher in patients with amputation versus those without amputation (19.9% vs. 7.3%; P=0.0001). Mean allograft survival was 60.97±0.67 months in non-African Americans without amputation versus 55.7±0.65 months in non-African Americans with amputation. Allograft survival was 59.73±0.13 months in African Americans without amputation versus 54.9±1.06 months in African Americans with amputation. In patients with amputation, race did not have any impact. Infectious complications were noted in 39 patients leading to death. CONCLUSIONS: Amputation is associated with decreased allograft and patient survival. Early detection and preventive strategies for PVD may decrease amputation rate and improve survival.

Effect of peripheral vascular disease on kidney allograft outcomes: a study of U.S. Renal data system.

BACKGROUND: The U.S. Renal Data System was used to analyze renal allograft outcomes in patients with peripheral vascular disease (PVD) at the time of transplant listing. METHODS: We used an incident cohort of patients who underwent renal transplantation between June 2004 and September 2009. We defined PVD as symptomatic PVD at wait-listing. Comorbid conditions were diabetes mellitus, ischemic heart disease, cerebrovascular disease, hypertension, and smoking. Chi-square test, Student's t test, and Cox regression were used for statistical associations. RESULTS: The mean graft survival was 55.3±0.40 months in patients with PVD versus 60.8±0.06 months in patients without PVD. There was an increased risk of graft failure with PVD (hazard ratio, 2.01; 95% confidence interval, 1.83-2.21; P=0.0001). After adjusting for other variables, PVD remained an independent risk factor for graft failure. Patients with PVD had lower death-censored graft survival versus patients without PVD at 1 year (93.3% vs. 96.6%), 2 years (89.7% vs. 95%), and 3 years (87.2% vs. 93.7%). All-cause mortality was higher in PVD versus without PVD (6.2% vs. 3.0%). In African Americans, the mean allograft survival was 54.8±0.98, months with PVD versus 59.7±0.135 months without PVD (P=0.0001). In non-African Americans, the mean allograft survival was 55.4±0.44 months with PVD versus 61.1±0.069 months without PVD (P=0.0001). There were no differences in survival between African Americans with PVD and non-African Americans with PVD. CONCLUSIONS: Patients with PVD have inferior allograft and patient survival versus those without PVD. Caution should be exercised when placing patients with symptomatic PVD or amputation on the wait-list.

Practice patterns in evaluation of living kidney donors in United Network for Organ Sharing-approved kidney transplant centers.

INTRODUCTION: The current pattern of evaluation for living kidney donors was investigated. METHODS: We designed a 37-question electronic survey to collect information about living kidney donor evaluation. Of the 181 United Network for Organ Sharing (UNOS)-approved centers, 72 responded. Survey responses were coded and downloaded into SPSS. Data was expressed as means and standard deviations or the percentage of centers with specific responses. RESULTS: 66% of the centers used a cut-off of <80 ml/min for exclusion of living kidney donors. 24-hour urine measuring creatinine clearance (CrCl) was the most common screening method for glomerular filtration rate (GFR) assessment in potential living donors. 56% of the centers excluded donors with blood pressure (BP) >140/90, whereas 22.7 and 7.1% excluded patients with pre-hypertension with a cut-off BP of 130/85 and 120/80, respectively. 66% of the centers used 24-hour urine creatinine to assess for proteinuria. 20% of the centers accepted living kidney donors with microalbuminuria and 84% accepted patients with a history of nephrolithiasis. 24% of the centers reported use of formal cognitive testing of potential living donors. DISCUSSION: There were significant variations in exclusion criteria based on GFR, history of kidney stones, body mass index, BP and donors with urinary abnormalities. The definitions for hematuria and proteinuria were variable. There is a need for uniformity in selection and for a living donor registry. We also recommend raising the cut-off for estimated GFR to 90 ml/min to account for 10-15% overestimation when CrCl is used.

Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines.

BACKGROUND: The F11 Receptor (F11R; aka JAM-A, JAM-1) is a cell adhesion protein present constitutively on the membrane surface of circulating platelets and within tight junctions of endothelial cells (ECs). Previous reports demonstrated that exposure of ECs to pro-inflammatory cytokines causes insertion of F11R molecules into the luminal surface of ECs, ensuing with homologous interactions between F11R molecules of platelets and ECs, and a resultant adhesion of platelets to the inflamed ECs. The main new finding of the present report is that the first step in this chain of events is the de-novo transcription and translation of F11R molecules, induced in ECs by exposure to inflammatory cytokines. METHODS: The experimental approach utilized isolated, washed human platelet suspensions and cultured human venous endothelial cells (HUVEC) and human arterial endothelial cells (HAEC) exposed to the proinflammatory cytokines TNF-alpha and/or IFN-gamma, for examination of the ability of human platelets to adhere to the inflamed ECs thru the F11R. Our strategy was based on testing the effects of the following inhibitors on this activity: general mRNA synthesis inhibitors, inhibitors of the NF-kappaB and JAK/STAT pathways, and small interfering F11R-mRNA (siRNAs) to specifically silence the F11R gene. RESULTS: Treatment of inflamed ECs with the inhibitors actinomycin, parthenolide or with AG-480 resulted in complete blockade of F11R- mRNA expression, indicating the involvement of NF-kappaB and JAK/STAT pathways in this induction. Transfection of ECs with F11R siRNAs caused complete inhibition of the cytokine-induced upregulation of F11R mRNA and inhibition of detection of the newly- translated F11R molecules in cytokine-inflamed ECs. The functional consequence of the inhibition of F11R transcription and translation was the significant blockade of the adhesion of human platelets to inflamed ECs. CONCLUSION: These results prove that de novo synthesis of F11R in ECs is required for the adhesion of platelets to inflamed ECs. Because platelet adhesion to an inflamed endothelium is crucial for plaque formation in non-denuded blood vessels, we conclude that the de-novo translation of F11R is a crucial early step in the initiation of atherogenesis, leading to atherosclerosis, heart attacks and stroke.

Incidence, predictors, costs, and outcome of renal cell carcinoma after kidney transplantation: USRDS experience.

INTRODUCTION: We carried out an analysis of the United States Renal Data System to determine the incidence, risk factors, prognosis, and costs associated with the diagnosis of renal cell carcinoma (RCC) after kidney transplantation. METHODS: This is a retrospective cohort of 40,821 Medicare primary renal transplant recipients transplanted from January 1, 2000, to July 1, 2005, and followed up till December 31, 2005, excluding those with prior RCC or nephrectomy. Kaplan-Meier analysis was performed to determine the time of occurrence of RCC, and Cox regression was used to determine factors associated with RCC. RESULTS: Three hundred sixty-eight patients were diagnosed with RCC within 3 years after transplant (incidence of 3.16 per 1000 person years). The 3-year incidence of RCC posttransplant was 9.29 per 1000 person years (2.3%) for those with pretransplant cysts and 3.08 per 1000 person years (0.7%) without pretransplant cysts. RCC was diagnosed disproportionately early posttransplant in patients with cysts. Cysts were independently associated with increased risk of RCC, as was male gender, older recipient, donor age, African American recipient, increased time on dialysis and acute rejection within first year posttransplant. RCC was associated with increased risk of mortality with a higher risk with pretransplant cysts. Patients who developed RCC had higher cumulative median costs ($55,456 at 2 years) than those who did not develop RCC ($40,369). There was no "clustering" of RCC in individual states or centers more than would be expected by chance. CONCLUSION: RCC was diagnosed disproportionately early in patients with pretransplant renal cysts and was associated with a worse prognosis and increased costs.

Prevalence and associations of anemia of CKD: Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999-2004.

BACKGROUND: Early identification of anemia of chronic kidney disease may be important for the development of preventive strategies. We compared anemia prevalence and characteristics in the National Kidney Foundation Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999-2004 populations. METHODS: Clinical, demographic, and laboratory data were collected from August 2000 to December 31, 2006, from participants in KEEP, a community-based health-screening program targeting individuals 18 years and older with diabetes, hypertension, or family history of kidney disease, diabetes, or hypertension. Anemia was defined as hemoglobin level less than 13.5 g/dL for men and less than 12.0 g/dL for women (Kidney Disease Outcomes Quality Initiative [KDOQI] 2006) or less than 13.0 g/dL for men and less than 12.0 g/dL for women (World Health Organization [WHO]). RESULTS: In KEEP (n = 70,069), 68.3% of participants, and in NHANES (n = 17,061), 52% of participants, were women. African Americans represented 33.9% of the KEEP and 11.2% of the NHANES cohorts, and Hispanics comprised 12.4% of KEEP and 13.2% of NHANES. Using the KDOQI classification, anemia was present in 13.9% and 6.3% of KEEP and NHANES participants, whereas using the WHO classification, anemia was present in 11.8% and 5.3%, respectively. In adjusted analysis of KEEP data, KDOQI-defined anemia was significantly more likely in men (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.23 to 1.37); this pattern was reversed when using WHO-defined anemia (OR, 0.68; 95% CI, 0.64 to 0.72). Adjusted odds of anemia were greater for African American than white KEEP participants (OR, 2.98; 95% CI, 2.80 to 3.16; OR, 3.00; 95% CI, 2.81 to 3.20 for KDOQI- and WHO-defined anemia, respectively). CONCLUSION: Anemia was twice as common in the targeted KEEP chronic kidney disease screening program cohort than in the NHANES sample population. African Americans had a 3-fold increased likelihood of anemia compared with whites. Targeted screening can identify anemia in a high-risk population.

Frequency of swing-segment stenosis in referred dialysis patients with angiographically documented lesions.

BACKGROUND: The segment of the vein mobilized for arterial anastomosis in the creation of an arteriovenous fistula (AVF) is the swing segment. This segment may experience turbulent flow and altered shear mechanical stress that result in stenosis. We sought to determine the frequency of stenotic lesions in the swing segment. STUDY DESIGN: Case series. SETTINGS & PARTICIPANTS: From January 31, 2003, to June 30, 2005, records of all patients referred to an outpatient hemodialysis vascular access center for AVF dysfunction were reviewed (n = 484). Of these, 278 patients had angiographically documented stenosis (any degree of luminal narrowing) on their first visit. OUTCOMES & MEASUREMENTS: Distribution of stenoses in different segments of the AVF. Swing-segment stenoses were classified as proximal (outflow into axillary vein system), distal or juxta-anastomotic (adjacent to the anastomosis), and the cephalic arch. RESULTS: Overall prevalence of angiographically documented swing segment stenosis (proximal, distal or juxta-anastomotic, and cephalic arch) was 45.7% (127 of 278 patients), whereas the remaining stenoses (151 of 278 patients) were distributed among the puncture zone, arterial, arterial anastomosis, and central veins. The most frequent location of the swing-segment stenosis was juxta-anatomosis (63%; 80 of 127 patients), followed by cephalic arch (19%; 24 of 127 patients) and proximal swing segment (18%; 23 of 127 patients). The distribution of swing-segment stenosis (n = 127) was equivalent among the various fistulas (brachial-cephalic, 35.4%; radial-cephalic, 33.9%; and brachial-basilic, 30.7%). Eighty-three percent of swing-segment stenoses were significant (>50% luminal narrowing) and underwent percutaneous transluminal angioplasty, with a 93% success rate. LIMITATIONS: Retrospective nature of the study and potential selection bias. CONCLUSION: In our population, swing-segment stenosis is the most common lesion in dysfunctional AVFs; juxta-anastomotic stenosis is the predominant lesion independent of fistula type. Whether the occurrence of swing-segment stenosis is caused by mobilization of the vein during surgery is not clear.

Association of plasma levels of F11 receptor/junctional adhesion molecule-A (F11R/JAM-A) with human atherosclerosis.

OBJECTIVES: The purpose of this study was to determine the association of the F11 receptor (F11R) with human vascular disease. BACKGROUND: A molecule identified as critical for platelet adhesion to a cytokine-inflamed endothelial surface in vitro is F11R. The F11R is known to be expressed in platelets and endothelium and reported recently to be overexpressed in atherosclerotic plaques. METHODS: A novel enzyme-linked immunosorbent assay was developed for the measurement of soluble F11R in human plasma. The F11R levels, along with a number of other biomarkers, were measured in 389 male patients with known or suspected coronary artery disease (CAD) undergoing coronary angiography at a Veterans Administration Medical Center. RESULTS: Patients with normal or nonobstructive disease (CAD angiographic score of 0), mild-to-moderate disease (score of 1 to 3), and severe disease (score of 4 to 6) had median F11R plasma levels of 38.6 pg/ml (mean 260 +/- 509.6 pg/ml), 45.2 pg/ml (mean 395.3 +/- 752.7 pg/ml), and 105.8 pg/ml (mean 629 +/- 831.7 pg/ml), respectively (p = 0.03). By multivariate analysis, the variables independently associated with CAD score were age, hyperlipidemia, chronic renal insufficiency, left ventricular function, and plasma F11R levels. The F11R was the only biomarker that was independently associated with CAD score. Consistent with the previously reported effects of tumor necrosis factor (TNF)-alpha on F11R expression in cultured endothelial cells, F11R levels correlated strongly with plasma TNF-alpha levels (r = 0.84; p < 0.0001). CONCLUSIONS: Plasma F11R is independently associated with the presence and severity of angiographically defined CAD. By virtue of its strong correlation to plasma TNF-alpha, F11R may be an important mediator of the effects of inflammation on the vessel wall. Strategies that block F11R may represent a novel approach to the treatment of human atherosclerosis.

Hypertension after renal transplant.

Hypertension is common after renal transplant and is associated with adverse graft and patient outcomes. A thorough understanding of the unique factors that operate in renal transplant recipients is essential for the proper evaluation and management of this disorder. In this review, the authors outline the pathogenesis, diagnostic workup, and treatment of hypertension after renal transplant.