IL-18 is involved in vascular injury in end-stage renal disease patients

Porażko, Tomasz; Kuźniar, J; Kusztal, Mariusz; Kuźniar, Tomasz J.; Weyde, Wacław; Kuriata-Kordek, Magdalena; Klinger, Marian

doi:10.1093/ndt/gfn486

Cited by 38 publications

(36 citation statements)

References 44 publications

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“…Our findings are in contrast with a Polish study demonstrating that hs-CRP, IL-18 and fetuin can explain the variability in PWV values in 102 subjects on renal replacement therapy compared to 30 healthy controls [7]. The authors used a similar cohort and design to the current study, however the prevalence of diabetes was lower (21 vs. 34%, respectively), and patients with a history of CVD or congestive heart failure were excluded from enrollment.…”

Section: Discussioncontrasting

confidence: 65%

“…There is currently much interest in elucidating the etiology, pathogenesis and potential reversibility of arterial stiffness, so that logical strategies to reduce the high mortality rate in these individuals can be tested. There are several clinical factors associated with PWV in the CKD population [2,3], and currently investigators are starting to focus on factors leading to arterial stiffness at the molecular level [4,5,6,7,8]. This study aimed to measure a set of inflammatory, vascular and cardiac biomarkers in a cohort of CKD patients with established diabetes and/or cardiovascular disease (CVD) to describe the relationship between these biomarkers and vascular stiffness (as measured by PWV).…”

Section: Introductionmentioning

confidence: 99%

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Novel Biomarkers Do Not Correlate with Severity of Vascular Stiffness in CKD Patients with Severe Co-Morbid Disease

Weber¹,

Sigrist²,

Romann³

et al. 2011

Nephron Clin Pract

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Background/Aims: Novel biomarkers may help explain the pathobiology of vascular disease in chronic kidney disease, and thus set the stage for identification of therapeutic targets, potential reversibility, and improved outcomes in this population. Methods: 124 subjects with GFR <60 ml/min or on renal replacement therapy underwent measurement of inflammatory, vascular and cardiac biomarkers as well as aortic pulse wave velocity (PWV) testing. A subset of patients (n = 60) had repeat PWV measured at 6 months. Results: Thirty-four percent of the patients were diabetic, and 50% had a history of cardiovascular disease or congestive heart failure. Median PWV was 9.8 (IQR 8.3–12.7) m/s. No significant correlations between the measured biomarkers and baseline PWV was observed. An increase in PWV (>1.5 m/s) over 6 months was observed in those subjects with diabetes, a higher brain natriuretic peptide level, lower cholesterol and lower phosphate level. Age (HR 1.086, p = 0.0028), fetuin (0.024, p = 0.0448), and interleukin-10 (top tertile HR 4.720, p = 0.0359) were associated with mortality. Conclusions: In this cohort of patients with chronic kidney disease and diabetes and/or heart disease, we were unable to demonstrate that select biomarkers can inform processes leading to vascular disease. Biomarkers do appear to have utility in predicting future events in this population.

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Section: Discussioncontrasting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Novel Biomarkers Do Not Correlate with Severity of Vascular Stiffness in CKD Patients with Severe Co-Morbid Disease

Weber¹,

Sigrist²,

Romann³

et al. 2011

Nephron Clin Pract

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“…Future studies need to address whether medical staff should attempt to control inflammation primarily and lipids secondarily to lower rates of mortality associated with ESRD patients. Additionally, future studies should ascertain whether improvements in inflammation levels and nutritional status may help to improve clinical outcomes independent of lipid values [34]. …”

Section: Discussionmentioning

confidence: 99%

Reverse Epidemiology of Lipid-Death Associations in a Cohort of End-Stage Renal Disease Patients

Bowden

Bounty²,

Shelmadine³

et al. 2011

Nephron Clin Pract

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Background and Aims: Cardiovascular disease is the leading cause of death among end-stage renal disease (ESRD) patients with hypercholesterolemia as a major cause. A few studies have demonstrated counter-intuitive findings known as reverse epidemiology where normal levels of cholesterol are associated with higher levels of mortality. The purpose of this study was to determine if there are reverse epidemiological associations between lipid risk factors and mortality in ESRD patients. Methods: ESRD (n = 438) patients were recruited from 4 outpatient dialysis units. Patients were tracked for 36 months until study completion or death with mortality status as the outcome measure. Results: Analysis of covariance revealed significant differences at posttest and reverse epidemiological effects for total cholesterol (p = 0.0001), low-density lipoprotein cholesterol (LDL) (p = 0.023), LDL particle number (p = 0.0001), LDL size (p = 0.009), triglycerides (p = 0.0001), and very low-density lipoprotein cholesterol (p = 0.036). A step-wise linear regression revealed weak, but significant predictors of mortality with total cholesterol (β = 0.263, p = 0.017) and LDL (β = –0.177, p = 0.045). A Cox death hazard ratio revealed LDL size as a significant predictor of mortality in this study. Conclusions: Our study discovered reverse epidemiology in a number of lipid variables. Additionally regression revealed that LDL and total cholesterol were predictors of mortality with lower levels being more predictive of death.

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“…ESRD is characterized by a storm of inflammatory insults that are linked to many uremia-induced complications, including anemia, malnutrition, and vascular calcification (22). Vascular calcification and inflammation seem to be inextricably linked because vascular calcification results in inflammation and inflammation promotes vascular calcification (23)(24)(25). HGFIN, a growth factor initially cloned and characterized as osteoactivin in osteoblasts (1), has been identified as a regulator of macrophage activity and inflammation (12).…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Monocyte/Macrophage HGFIN (Gpnmb/Osteoactivin) Expression in End-Stage Renal Disease

Pahl

Vaziri²,

Yuan³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Background and objectives: Hematopoietic growth factor-inducible neurokinin 1 (HGFIN), also known as Gpnmb and osteoactivin, is a transmembrane glycoprotein that is expressed in numerous cells, including osteoclasts, macrophages, and dendritic cells. It serves as an osteoblast differentiation factor, participates in bone mineralization, and functions as a negative regulator of inflammation in macrophages. Although measurable at low levels in monocytes, monocyte-to-macrophage transformation causes substantial increase in HGFIN expression. HGFIN is involved in systemic inflammation, bone demineralization, and soft tissue vascular calcification.Design, setting, participants, & measurements: We explored HGFIN expression in monocytes and monocyte-derived macrophages in 21 stable hemodialysis patients and 22 control subjects.Results: Dialysis patients exhibited marked upregulation of colony-stimulating factor and IL-6 and significant downregulation of IL-10 in intact monocytes and transformed macrophages. HGFIN expression in intact monocytes was negligible in control subjects but conspicuously elevated (8.6-fold) in dialysis patients. As expected, in vitro monocyte-to-macrophage transformation resulted in marked upregulation of HGFIN in cells obtained from both groups but much more so in dialysis patients (17.5-fold higher). Upregulation of HGFIN and inflammatory cytokines in the uremic monocyte-derived macrophages occurred when grown in the presence of either normal or uremic serum, suggesting the enduring effect of the in vivo uremic milieu on monocyte/macrophage phenotype and function.Conclusions: Uremic macrophages exhibit increased HGFIN gene and protein expression and heightened expression of proinflammatory and a suppressed expression of anti-inflammatory cytokines. Further studies are needed to determine the role of heightened monocyte/macrophage HGFIN expression in the pathogenesis of ESRD-induced inflammation and vascular and soft tissue calcification.

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IL-18 is involved in vascular injury in end-stage renal disease patients

Abstract: The novel observations in the present study are the data indicating that the distinctive contribution of IL-18, but not IL-6, to the arteriosclerosis occurrence in CKD patients, is independent from CRP, fetuin A or other factors involved in the general inflammatory process.

Cited by 38 publications

References 44 publications

Novel Biomarkers Do Not Correlate with Severity of Vascular Stiffness in CKD Patients with Severe Co-Morbid Disease

Novel Biomarkers Do Not Correlate with Severity of Vascular Stiffness in CKD Patients with Severe Co-Morbid Disease

Reverse Epidemiology of Lipid-Death Associations in a Cohort of End-Stage Renal Disease Patients

Upregulation of Monocyte/Macrophage HGFIN (Gpnmb/Osteoactivin) Expression in End-Stage Renal Disease

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