Elevated serum levels of soluble adhesion molecules predict death in pre-dialysis patients: association with malnutrition, inflammation, and cardiovascular disease.

BACKGROUND: Atherosclerotic cardiovascular disease, malnutrition, and increased levels of pro-inflammatory cytokines are common features in patients with chronic renal failure, and contribute to the high mortality rate observed in these patients. A diverse group of soluble cellular adhesion molecules (CAM) (sVCAM-1, sICAM-1 and sE-selectin) are expressed on the surface of vascular endothelial cells in response to pro-inflammatory cytokines and may play an important role in the atherogenic process. METHODS: Serum levels of sVCAM-1, sICAM-1 (n=87) and sE-selectin (n=71) were analysed in a cohort of 88 patients (50+/-1 years) with chronic renal failure. The presence of malnutrition (subjective global assessment (SGA) and serum albumin), inflammation (C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), and serum hyaluronan), and cardiovascular disease (CVD) were assessed at a time-point close to the start of dialysis treatment (GFR 7+/-1 ml/min). Blood lipid parameters were also assessed. RESULTS: Significant correlations were observed between Log high-sensitivity CRP (hsCRP) and sVCAM-1 (R=0.39; P<0.01) and sICAM-1 (R=0.47; P:<0.001) levels but not between Log hsCRP and sE-selectin levels in 60 patients examined with a hsCRP assay. Also serum concentrations of Log hyaluronan correlated significantly to sVCAM-1 (R=0.34; P<0.01) and sICAM-1 (R=0.29; P<0.05) levels. Malnourished patients (SGA>1) had elevated serum concentrations of sVCAM-1 (1436+/-94 vs. 1105+/-53 ng/ml; P<0.01) compared to well-nourished patients (SGA 1). Patients with clinical signs of CVD (n=26) had elevated serum levels of sICAM-1 (282+/-18 vs. 242+/-9 ng/ml; P<0.05) compared to 61 patients without signs of CVD. Plasma Log lipoprotein (a) (Lp(a)) levels correlated significantly with sVCAM-1 (R=0.30; P<0.01). Survival analysis by the Cox regression model showed that elevated sICAM-1 was, independent of age, SGA, CVD, and Log CRP, significantly related to an increased mortality rate. CONCLUSIONS: Elevated serum concentrations of soluble adhesion molecules are found in pre-dialysis patients who are malnourished, inflamed, and have signs of cardiovascular disease. These data also suggest that sICAM-1 is an independent predictor of mortality in pre-dialysis patients. Further studies are needed to determine if inflammation causes accelerated atherogenesis via effects on soluble adhesion molecules or if elevated serum levels of soluble adhesion molecules are merely markers of endothelial activation in patients with chronic renal failure.     

Lower progression rate of end-stage renal disease in patients with peripheral arterial disease using statins or Angiotensin-converting enzyme inhibitors

Patients with peripheral arterial disease (PAD) are at increased risk for ESRD and cardiovascular events. The primary objective was to assess the association between ankle-brachial index (ABI) values and renal outcome. The secondary objective was to evaluate whether statins and angiotensin-converting enzyme inhibitors (ACEI) are associated with improved renal and cardiovascular outcome in patients with PAD. In a prospective observational cohort study of 1940 consecutive patients with PAD, ABI was measured and chronic statin and ACEI therapy was noted at baseline. Serial creatinine concentrations were obtained at baseline, 6 mo, and every year after enrollment. End points were ESRD, all-cause mortality, and cardiac events during a median follow-up period of 8 yr. Baseline estimated GFR <60 ml/min per 1.73 m(2) was assessed in 27% of patients. ESRD, all-cause mortality, and cardiac events occurred in 10, 46, and 31% of patients, respectively. In multivariate analysis, a lower baseline ABI was significantly associated with a higher progression rate of ESRD (hazard ratio [HR] per 0.10 decrease 1.34; 95% confidence interval [CI] 1.21 to 1.49). Chronic use of statins and ACEI were significantly associated with lower ESRD (HR 0.41 [95% CI 0.28 to 0.63] and 0.74 [95% CI 0.54 to 0.98], respectively), mortality (HR 0.66; [95% CI 0.55 to 0.82] and 0.84 [95% CI 78 to 0.95], respectively), and cardiac events (HR 0.71 [95% CI 0.56 to 0.91] and 0.81 [95% CI 0.68 to 0.96], respectively). In patients with PAD, low ABI values independently predict the onset of ESRD. Less progression toward ESRD and improved cardiovascular outcome was observed among patients who were on long-term statins and ACEI.     

Circulating soluble adhesion molecules in ANCA-associated vasculitis.

BACKGROUND: To evaluate whether changes in concentrations of soluble (s) E-selectin, sP-selectin, sL-selectin, intercellular adhesion molecule 1 (sICAM-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in patients with chronic renal failure (CRF). SUBJECTS AND METHODS: A sandwich ELISA was used to measure these soluble adhesion molecules in (i) sera from 20 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granulomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtained at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis. RESULTS: At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88+/-42 ng/ml, 437+/-184 ng/ml, 1720+/-1174 ng/ml respectively) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P<0.0001, P=0.002 and P=0.001 respectively). Serum sP-selectin values did not differ from those obtained in normal donors. In contrast, sL-selectin levels (940+/-349 ng/ml) were significantly lower in patients than those recorded in healthy controls (P<0.0001). A significant decrease in concentrations of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 was observed between active and remission phases (P<0.0001, P=0.002, P=0.001 and P=0.001 respectively). No significant differences were observed in sL-selectin levels between active and remission phases. sL-selectin concentrations (802+/-306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P<0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-selectin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negative correlation was established between creatinine and sL-selectin concentration. CONCLUSIONS: Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 and decreased levels of sL-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remission phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels between active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF suggests that the mechanism of clearance of these molecules is not renal.     

High soluble vascular cell adhesion molecule-1 concentrations predict long-term mortality in hemodialysis patients

Purpose

Soluble vascular cell adhesion molecule-1 (sVCAM-1) has a strong association with cardiovascular deaths in patients with coronary artery disease. The aim of this study is to explore the association between sVCAM-1 and cardiovascular mortality in maintenance hemodialysis (MHD) patients.

Methods

Eighty-three clinically stable MHD patients (mean age of 59.4 ± 13.7 years) at a single hospital-based dialysis facility were included. sVCAM-1, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin) were determined at study baseline. The study cohort was divided into higher and lower concentration groups by the median value. The all-cause and cardiovascular mortality of this cohort were followed for 7 years.

Results

The mean concentrations of sVCAM-1, sICAM-1, and sE-selectin were 1,393.08 ± 300.96, 230.16 ± 84.86, and 60.01 ± 42.00 ng/mL, respectively. The higher concentration groups of sVCAM-1 and sICAM-1 had higher all-cause mortality by Kaplan–Meier analysis (p = 0.002 and p = 0.030, respectively). Higher sVCAM-1 concentrations had a higher risk of all-cause and cardiovascular mortality (p = 0.006 p = 0.046, respectively) in Cox proportional hazards model analysis.

Conclusion

In MHD patients, higher sVCAM-1 concentrations independently predict all-cause and cardiovascular mortality. This biomarker may be used as a valid surrogate marker for predicting outcomes.     

Chlamydia pneumoniae,overall and cardiovascular mortality in end-stage renal disease (ESRD)

BACKGROUND: Cross-sectional and retrospective studies suggest that Chlamydia pneumoniae infection may contribute importantly to the high cardiovascular risk of patients with end-stage renal disease (ESRD). METHODS: We investigated the relationship between C. pneumoniae serology and survival and incident fatal cardiovascular events in a cohort of 227 ESRD patients (follow-up of 39 +/- 20 months). RESULTS: On univariate Cox regression analysis patients with anti-C. pneumoniae immunogloblulin A (IgA) titer > or = 1:16 had a significantly higher risk of all-cause and cardiovascular mortality when compared to patients without IgA antibodies. However, after data adjustment for age and smoking, the hazard ratio (HR) decreased substantially and became largely nonsignificant. Adjustments for traditional and nontraditional risk factors further decreased the independent association of IgA anti-C. pneumoniae and these outcomes (all-cause mortality HR, 1.08; 95% CI, 0.68 to 1.72; P = 0.74; cardiovascular mortality HR, 1.07; 95% CI, 0.60 to 1.89; P = 0.83). A similar loss of prognostic power was observed for IgG anti-C. pneumoniae so that in fully adjusted models the HRs were very close to those observed for IgA anti-C. pneumoniae (all-cause mortality HR, 1.13; 95% CI, 0.68 to 1.86, P = 0.64; cardiovascular mortality HR, 1.10; 95% CI, 0.60 to 2.00; P = 0.77). CONCLUSION: C. pneumoniae seropositivity is associated to shorter survival and incident fatal cardiovascular events in patients with ESRD but these associations are in large part attributable to the link between C. pneumoniae and well-established, traditional risk factors. It is highly unlikely that C. pneumoniae infection is a major risk factor in patients with ESRD.     

Combined angiotensin-converting enzyme inhibition and receptor blockade associate with increased risk of cardiovascular death in hemodialysis patients

To compare the relative effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in reducing cardiovascular mortality in chronic hemodialysis patients, we conducted an observational analysis of all patients initiated on ACEI or ARB therapy undergoing chronic hemodialysis at a large dialysis provider. Survival curves with mortality hazard ratios (HRs) were generated using the Kaplan-Meier method and Cox regression. Outcomes were compared using inverse probability of treatment weighting and propensity score matching. Over 6 years, 22,800 patients were newly initiated on an ACEI and 5828 on an ARB after at least 60 days of chronic hemodialysis. After adjustment for baseline cardiovascular risk factors, there was no significant difference in the risk of cardiovascular, all-cause, or cerebrovascular mortality in patients initiated on an ARB compared with an ACEI (HR of 0.96). A third of 28,628 patients, newly started on an ACEI or ARB, went on to another antihypertensive medication in succession. After adjustment for risk factors, 701 patients initiated on combined ACEI and ARB therapy (HR of 1.45) or 6866 patients on ACEI and non-ARB antihypertensive agent (HR of 1.27) were at increased risk of cardiovascular death compared with 1758 patients initiated on an ARB and non-ACEI antihypertensive therapy. Thus, an ARB, in combination with another antihypertensive medication (but not an ACEI), may have a beneficial effect on cardiovascular mortality. As observational studies may be confounded by indication, even when adjusted, randomized clinical trials are needed to confirm these findings.     

Hemodialysis procedure does not affect the levels of sICAM-1 and sVCAM-1 in patients with end stage renal disease

Atherosclerosis is by far the leading cause of mortality and morbidity in patients with end stage renal disease undergoing chronic hemodialysis (HD). Vascular endothelial cell adhesion molecules like the intercellular adhesion molecule-1 (ICAM-1) and the vascular cell adhesion molecule-1 (VCAM-1) are involved in the pathogenesis of atherosclerosis. Their soluble forms (sICAM-1, sVCAM-1) are considered potential serum markers of endothelial activation and atherosclerosis. The aim of this study was to clarify the influence of the HD procedure on the levels of sICAM-1 and sVCAM-1 in patients with end stage renal disease. We evaluated 35 clinically stable patients (18 males, 17 females, mean age 61 +/- 12) on chronic HD treatment. Diabetes mellitus coexisted in eight patients and arterial hypertension in 23 patients. Blood was drawn before, every hour during, and after a single HD session in each patient. Low-flux cuprophane dialyzers (GFS 12, Gambro, Lund, Sweden) were used in 22 and high-flux polysulfone dialyzers (Hemoflow F 60S, Fresenius, Oberursel, Germany) in 13 cases. At 30 min into the HD session (n=31, 20 low-flux HD, 11 high-flux HD) blood was drawn simultaneously from the entrance and the exit line of the dialyzer. From all these samples, serum concentrations of sICAM-1 and sVCAM-1 were determined by commercially available enzyme immunoassays (ELISA, R&D Systems, Minneapolis, USA). Results were corrected according to hemoconcentration, where appropriate. Plasma levels of sVCAM-1 were elevated in patients with end stage renal disease before the beginning of the dialysis session when compared to healthy controls (1449 +/- 497 ng/mL vs. 691 +/- 118 ng/mL). On the contrary, such an elevation was not found in the case of sICAM-1 (231 +/- 58.5 ng/mL vs. 236.4 +/- 96.8 ng/mL in healthy controls). These levels remained stable in all measurements throughout the dialysis procedure. Furthermore, serum sICAM-1 and sVCAM-1 levels remained unaltered after the passage of the dialyzer. The levels of sICAM-1 and sVCAM-1 were not influenced by the existence of diabetes mellitus, hypertension, or by the utilization of biocompatible, high flux dialyzers. Our study confirms that in chronic HD patients serum levels for sVCAM-1 are elevated. The levels of adhesion molecules are not affected by the HD procedure. These findings probably can be attributed to a decreased renal clearance or catabolism of sICAM-1 and sVCAM-1 and to the different sources of the two molecules. Neither coexisting diabetes mellitus nor arterial hypertension influences the circulating levels of these adhesion molecules. The functional role of sVCAM-1 and sICAM-1, the exact renal contribution to their metabolism, and their role as markers of atherosclerosis in chronic renal disease need further evaluation.     

Inflammation and outcome in end-stage renal failure: does female gender constitute a survival advantage?

BACKGROUND: Elevated C-reactive protein (CRP) is a strong predictor of cardiovascular events and all-cause mortality in end-stage renal disease (ESRD) patients. However, although sex hormones may influence serum levels of inflammatory proteins, gender has not been taken into consideration in previous studies of inflammation and outcome in ESRD patients. METHODS: We included 663 (374 males) ESRD patients (59 +/- 1 year) from three European renal centers (Sweden, Germany and Italy) in which CRP levels and outcome data (follow-up 33 +/- 1 months) were available. The relation between outcome and serum levels of the soluble intercellular adhesion molecule (sICAM-1) was evaluated in 312 of the patients. RESULTS: The present study shows that elevated CRP is a strong predictor of outcome, but whereas no difference in all-cause mortality was observed between non-inflamed (CRP 相似文献   

Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) reduce cardiovascular death in the general population, but data for renal transplant recipients remain elusive. Similarly, ACEI/ARB have been shown to reduce proteinuria, but data on graft survival are lacking. Therefore a retrospective open cohort study was conducted of 2031 patients who received their first renal allograft at the Medical University of Vienna between 1990 and 2003 and survived at least 3 mo. Patient and graft survival was compared between patients with versus without ACEI and/or ARB therapy. Data were analyzed with and without propensity score models for ACEI/ARB therapy. Medication and comorbidities were analyzed as time-dependent variables in the Cox regression analyses. Ten-year survival rates were 74% in the ACEI/ARB group but only 53% in the noACEI/ARB group (P<0.001). The hazard ratio (HR) of ACEI/ARB use for mortality was 0.57 (95% confidence interval [CI] 0.40 to 0.81) compared with nonuse. Ten-year actual graft survival rate was 59% in ACEI/ARB patients but only 41% in nonusers (P=0.002). The HR of actual graft failure for ACEI/ARB recipients was 0.55 (95% CI 0.43 to 0.70) compared with nonusers; the HR of functional graft survival was 0.56 (95% CI 0.40 to 0.78). Ten-year unadjusted functional graft survival rates were 76% among ACEI/ARB patients and 71% in noACEI/ARB recipients (P=0.57). In summary, the use of ACEI/ARB therapy was associated with longer patient and graft survival after renal transplantation. More frequent use of these medications may reduce the high incidence of death and renal allograft failure in these patients.     

Systemic and vascular inflammation is elevated in early IgA and type 1 diabetic nephropathies and relates to vascular disease risk factors and renal function.

BACKGROUND: Inflammation is implicated in cardiovascular disease (CVD) and mortality in end-stage renal failure (ESRF). Its importance in early renal disease is yet to be defined. METHODS: Serum levels of systemic and vascular inflammatory markers in early IgA nephropathy (IgAN) and control subjects were measured and related to renal function and vascular risk factors. A parallel study in type 1 diabetes mellitus subjects with (T1DM Nx) and without nephropathy (T1DM No Nx) was performed. RESULTS: Fifty-one IgAN patients aged 46+/-2 years (mean+/-SEM), calculated creatinine clearance (CrCl) 88+/-5 ml/min, were compared with 51 matched control subjects. Forty-six T1DM Nx patients aged 40+/-2 years, CrCl 84+/-5 ml/min, and 73 T1DM No Nx patients aged 38+/-2 years were also compared. High sensitivity C-reactive protein (hsCRP) was elevated in IgAN, T1DM Nx and T1DM No Nx patients compared with controls [4.2+/-0.6 (P < 0.001), 4.1+/-0.6 (P < 0.001), 2.6+/-0.4 (P < 0.05) vs 1.6+/-0.3 mg/l]. Levels in T1DM Nx patients were higher than in T1DM No Nx patients (P < 0.05). Inflammation and vascular dysfunction as measured by pulse pressure (PP) were related. HsCRP correlated with PP in IgAN and T1DM Nx (r = 0.47, P = 0.001; r = 0.40, P < 0.05). PP was the strongest independent predictor of hsCRP in IgAN (T = 2.45, P < 0.001), while body mass index (T = 7.83, P < 0.001) was the strongest predictor in T1DM Nx. Endothelial cell adhesion molecules were increased in T1DM Nx > IgAN > T1DM No Nx vs controls: soluble vascular adhesion molecule-1 (sVCAM-1) 760+/-30 (P < 0.001) > 663+/-34 (P = 0.001) > 601+/-21 (P < 0.05) vs 536+/-15 ng/ml; soluble intracellular adhesion molecule-1 (sICAM-1) 320+/-8 (P < 0.001) > 313+/-13 (P < 0.001) > 307+/-8 (P < 0.001) vs 244+/-6 ng/ml. sVCAM-1 levels were higher in T1DM Nx than in T1DM No Nx, P < 0.001. In IgAN and T1DM Nx, hsCRP correlated with sICAM-1 (r = 0.33, P = 0.017; r = 0.37; P = 0.017). sVCAM-1 was related to renal function in IgAN and T1DM Nx: serum cystatin C (r = 0.63, P < 0.001: r = 0.425, P = 0.002), and urine protein:creatinine ratio in IgAN (r = 0.48; P = 0.001). CONCLUSIONS: Systemic and vascular markers of inflammation are increased in early renal disease and relate to renal dysfunction and cardiovascular risk factors. Inflammation may be a common process in various renal diseases and may link and accelerate renal dysfunction and CVD.     

Effect of calcium channels blockers and inhibitors of the renin-angiotensin system on renal outcomes and mortality in patients suffering from chronic kidney disease: systematic review and meta-analysis

Background: The renoprotective effect of inhibitors of renin-angiotensin system (RAS) has been identified through placebo-controlled trials. However, the effect of calcium-channel blockers (CCBs) on renal system is still controversial. Our current meta-analysis includes available evidences to compare the effect of dihydropyridine CCBs and ACEIs or ARBs on renal outcomes and mortality. We also further investigate whether CCBs can be used in combination with inhibitors of RAS to improve the prognosis of patients with chronic kidney disease (CKD). Methods and results: Electronic databases were searched up to July 2012, for clinical randomized controlled trials, assessing the effect of dihydropyridine CCBs on the incidence of end-stage renal disease (ESRD) and all-cause mortality in contrast to ACEIs or ARBs. Eight clinical trials were included containing 25,647 participants. ESRD showed significantly higher frequency with CCBs therapy compared with ACEIs or ARBs therapy, though blood pressure was decreased similarly in both groups in every trial (OR, 1.25; 95% CI, 1.05–1.48; p?=?0.01). In contrast, there was no significant difference in the incidence of all-cause mortality between these two groups, though ACEIs or ARBs exhibited better renoprotective effect compared to CCBs (OR, 0.96; 95% CI, 0.89–1.03; p?=?0.24). Conclusions: CCBs did not increase all-cause mortality incidence in patients with CKD though they displayed weaker renoprotective, compared to ACEIs or ARBs therapy. Our results suggest the combination of a CCB and an ACEI or ARB should be a preferable antihypertensive therapy in patients with CKD, considering their higher effect in decreasing blood pressure and fewer adverse metabolic problems caused.     

Increased levels of soluble TNF-alpha receptors and cellular adhesion molecules in patients undergoing bioincompatible hemodialysis

BACKGROUND: The study aimed to differentiate the effects of hemodialysis (HD) and chronic renal failure (CRF) on the levels of circulating tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha receptors p55 and p75, soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), soluble endothelial-leukocyte adhesion molecule-1 (sE-selectin) and sP-selectin in 18 patients on regular HD treatment with cuprophane membrane in relation to 15 non-dialyzed CRF patients and 15 healthy controls. METHODS: The serum concentrations were determined with standard ELISA assays. RESULTS: Blood serum p75 and p55 were approximately tenfold increased in CRF (36.7 +/- 6.2 and 27.1 +/- 5.6 ng/ml) and HD patients (45.6 +/- 18.4 and 28.7 +/- 5.9 ng/ml) before the HD session (HD 0), during (HD 20) the session (45.7 +/- 18.4 and 28.5 +/- 7.3 ng/ml) and after (HD 240) the HD session (52.1 +/- 17.4 and 30.9 +/- 8.2 ng/ml) in comparison to control values (5.6 +/- 1.3 and 2.4 +/- 0.8 ng/ml, respectively) (p < 0.01). The highest increment of p75 at the end of HD session (HD 240) was also significantly higher than at preceding time points (HD 0 and 20) (p < 0.05). However, the remaining study parameters did not change during an HD session. Also, there were no relevant changes in TNF-alpha levels if (HD 0) 22.7 +/- 21.5 ng/ml and (HD 240) 21.1 +/- 18.9 ng/ml were compared. Chronic HD status was related to the increase of sVCAM-1 and sICAM-1 levels. Prior to HD, T0 sVCAM-1 and sICAM-1 concentrations were 2,180.4 +/- 761.8 and 567.3 +/- 218.8 ng/ml, during HD (T20): 2,172.7 +/- 759.2 and 602.3 +/- 379.9 ng/ml, and after HD (T240): 2,401.6 +/- 756.4 and 648.3 +/- 183.5 ng/ml, respectively (p < 0.05 vs. controls and CRF patients). sVCAM-1 and sICAM-1 serum levels (1,262.2 +/- 472.9 and 165.6 +/- 50.4 ng/ml) were similar in CRF patients and healthy controls (854.4 +/- 241.5 and 217.6 +/- 74.2 ng/ml, respectively). Even though serum sE- and sP-selectin in CRF patients did not differ from the control (39.8 +/- 21.3 vs. 42.1 +/- 18.9 ng/ml and 187.9 +/- 66.9 vs. 198.8 +/- 62.2 ng/ml, respectively), their levels were increased in HD patients up to 111.9 +/- 54.6 and 453.2 +/- 231.1 ng/ml in patients prior to HD, 118.7 +/- 66.2 and 350.8 +/- 114.8 ng/ml during the HD session and then 132.3 +/- 61.1 and 368.3 +/- 126.6 ng/ml, respectively, after its completion (p < 0.05 in comparison with CRF patients and controls). CONCLUSIONS: The increased circulating TNF-alpha receptors appear more associated with the uremic milieu than HD-related systemic inflammation, whereas increased soluble cellular adhesion molecules in patients undergoing bioincompatible HD may be related to the enhanced systemic inflammation specifically due to maintenance HD.     

Impact of use of angiotensin II receptor blocker on all-cause mortality in hemodialysis patients: prospective cohort study using a propensity-score analysis

Background

It is controversial whether treatment with an angiotensin II receptor blocker (ARB) or a calcium channel blocker (CCB) improves prognosis of hemodialysis (HD) patients.

Methods

This study was designed as a multicenter prospective cohort study. HD patients (n = 1071) were enrolled from 22 institutes in January 2009 and followed up for 3 years. Patients with missing data, kidney transplantation or retraction of consent during the follow-up period (n = 204) were excluded, and 867 patients contributed to analysis of mortality. Propensity score (PS) for use of ARB and that for CCB was calculated using a multiple logistic regression model.

Results

ARB and CCB were prescribed in 45.6 and 54.7 % of patients at enrollment. During the 3-year follow-up period, all-cause mortality and cardiovascular mortality rates were 18.8 and 5.1 %, respectively. Kaplan–Meier curves showed that all-cause and cardiovascular mortality rates were lower in the ARB group than in the non-ARB group, though the mortality rates were similar in the CCB group and non-CCB group. In PS-stratified Cox regression analysis, ARB treatment was associated with 34 and 45 % reduction of all-cause death and cardiovascular death, respectively. In PS matching analysis, ARB treatment was associated with a significant reduction (46 % reduction) in the risk of all-cause death. A significant impact of CCB treatment on all-cause or cardiovascular mortality was not detected in PS analysis.

Conclusions

The use of an ARB, but not a CCB, is associated with reduced all-cause and cardiovascular mortalities in patients on HD.

     

Serum concentration of adhesion molecules in postoperative biliary atresia patients: relationship to disease activity and cirrhosis

BACKGROUND/PURPOSE: Biliary atresia (BA) is associated with progressive liver fibrosis, which may be mediated by immunologic abnormalities involving adhesion molecules. This study investigates the relationship between serum intercellular adhesion molecule-1 (sICAM-1), serum vascular cell adhesion molecule-1 (sVCAM-1), and the clinical and histologic severity of BA. METHODS: Serum ICAM-1 and VCAM-1 levels were measured by enzyme-linked immunosorbent assay in 35 patients with BA and 20 healthy controls. Standard liver function tests (LFTs), and frozen section liver biopsy specimens were used to determine liver status. On the basis of LFT results, the BA patients were classified into group I (n = 10; normal LFTs), group II (n = 15; elevated LFTs, anicteric), and group III (n = 10; elevated LFTs, icteric). Eight subjects in group II, and all subjects in group III had portal hypertension (PH). RESULTS: sICAM-1 levels were significantly elevated in group III (1760.0 +/- 717.5 ng/mL) compared with group II (555.1 +/- 199.4 ng/mL), group I (272.1 +/- 59.9 ng/mL) and controls (256.3 +/- 71.6 ng/mL). Although sVCAM-1 levels were significantly elevated in group III (1932.9 +/- 282.6 ng/mL) compared with group II (1054.3 +/- 297.0 ng/mL), group I (605.4 +/- 112.4 ng/mL), and controls (616.0 +/- 112.0 ng/mL; P <.001), there was no statistically significant difference between groups I, II, or controls. sVCAM-1 levels were elevated significantly in BA subjects in group II with PH (1253.0 +/- 245.1 ng/mL) compared with those who did not have PH (827.3 +/- 151.7 ng/mL; P <.01). PH did not affect sICAM-1 levels. There was strong expression of ICAM-1 and VCAM-1 in proliferating bile ductules, endothelial cells, and liver cells in group III compared with group II and controls. CONCLUSIONS: In BA, sICAM-1 and sVCAM-1 levels could be useful as markers of end-stage liver disease, with sVCAM-1 being more specific for PH. Induction of ICAM-1 and VCAM-1 may be an important factor in the development of cirrhosis.     

The relationship between the method of cardioplegia and vascular endothelial cell derived soluble adhesion molecules in myocardial ischemia-reperfusion injury

The relative role of different adhesion molecules in the ischemia-reperfusion injury after cardioplegic arrest in the clinical setting is unknown, because of protective effects of cardioplegia and hypothermia. The aim of this study is to determine the relationship between the method of the cardioplegia and endothelial derived soluble adhesion molecules; soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in myocardial ischemia- reperfusion injury. Fourteen male patients who underwent aortocoronary bypass surgery with cardiopulmonary bypass were included in this study. They were randomised to be given blood or crystalloid cardioplegia for myocardial protection. Group I (n=7) received blood cardioplegia and group II (n=7) received crystalloid cardioplegia. The cross-clamp times were not significantly different between the two groups, 49.4+/-4.6 min for group I and 54.8+/-2.5 min for group II. Mean age of patients was 58+/-2.1 years for group I and 54+/-2.6 years for group II. Blood samples were taken from both the aorta and coronary sinuses of all patients before cross-clamp, after cross-clamping and at 30th min of reperfusion. Plasma were obtained from blood samples and then stored at -70 degrees C. sVCAM-1 and sICAM-1 levels were measured by ELISA in the samples. There were no significant differences in the levels of sICAM-1 and sVCAM-1 at the beginning of reperfusion and at 30th min of reperfusion in coronary sinus of group I patients. But, increased sICAM-1 and sVCAM-1 levels were observed at 30th min of reperfusion in blood taken from coronary sinuses of group II patients compared with beginning of reperfusion (respectively p=0.01, p=0.03). In conclusion, these results have shown that ischemia-reperfusion injury is more likely to occur in patients protected by crystalloid cardioplegia, and suggest that blood cardioplegia may be preferred especially in borderline myocardial functioned patients.     

Impact of estimated glomerular filtration rate on the 15-year outcome after coronary artery bypass surgery.

OBJECTIVE: The aim of the present study was to evaluate the impact of estimated glomerular filtration rate (eGFR) on the 15-year outcome after coronary artery bypass surgery (CABG) in a community-wide population study. METHODS: Eight hundred and eighty-two patients who underwent CABG were included in this study. eGFR was estimated by the modified Modification of Diet in Renal Disease study equation. RESULTS: Among 30-day operative survivors, patients with eGFR<60 ml/min/1.73 m(2) had significantly poorer overall survival (at 5, 10 and 15 year, 84.7%, 63.5% and 43.8% vs 92.8%, 77.6% and 58.3%, respectively, p<0.0001). eGFR (HR 0.989, 95% CI 0.981-0.997, as well as eGFR<60 ml/min/1.73 m(2): HR 1.470, 95% CI 1.092-1.979) was an independent predictor of late all-cause mortality only when patients' age was excluded from the regression model. This was probably due to strong impact of age on eGFR. eGFR (HR 0.987, 95% CI 0.975-0.998, as well as eGFR<60 ml/min/1.73 m(2); HR 1.612, 95% CI 1.086-2.395) was an independent predictor of cardiovascular mortality secondary to ischemic heart disease or ischemic stroke. eGFR (HR 0.991, 95% CI 0.983-0.999, as well as eGFR<60 ml/min/1.73 m(2): HR 1.396 95% CI 1.031-1.891) was an independent predictor of cardiovascular mortality and morbidity (myocardial infarction, stroke, need for redo CABG or PCI). When both preoperative serum creatinine and eGFR were included in the regression model, only eGFR was predictive of all-cause mortality, cardiovascular mortality and combined cardiovascular mortality and morbidity. CONCLUSIONS: This study showed that an eGFR<60 ml/min/1.73 m(2) is an important determinant of long-term outcome after isolated CABG. Since its predictive value seems to be superior to serum creatinine, eGFR may be useful to identify those patients undergoing CABG with subclinical chronic kidney disease.     

Long term angiotensin converting enzyme-inhibition in patients after coronary artery bypass grafting reduces levels of soluble intercellular cell adhesion molecule-1.

OBJECTIVE: to examine the effect of angiotensin converting enzyme inhibition (ACEI) on soluble intercellular adhesion molecule 1 (sICAM-1) and C-reactive protein (CRP) in patients requiring coronary artery bypass grafting (CABG). METHOD: subgroup analysis of 42 patients randomised to Quinapril (40 mg daily determined) and 45 to placebo. sICAM-1 and CRP were > or = 4 weeks before and 1 year after surgery. RESULTS: there was no difference in sICAM-1 at baseline (142.2 microg/L vs 136.6 microg/L). There was significant reduction in s-ICAM-1 in patients receiving quinapril (142.2+/-10.8 microg/L vs 125.6+/-9.4 microg/L, p<0.05) but not placebo (136.6+/-10.2 microg/L vs 131.2+/-11.7 microg/L, p=NS). Levels of C-reactive protein remained unchanged in both groups (3.70+/-0.85 vs 2.73+/-0.32 mg/L, 2.85+/-0.48 vs 3.16+/-0.50 mg/L). CONCLUSIONS: ACEI reduces sICAM-1 in patients undergoing CABG. The benefits of ACEI may partly be due to a reduction of the vascular inflammatory response.     

Blood pressure, antihypertensive treatment, and graft survival in kidney transplant patients

Whether the use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker inhibitor (ACEI/ARB) is beneficial in renal transplant recipients remains controversial. In this retrospective study on 505 renal transplant recipients, we analyzed blood pressure and graft survival according to antihypertensive treatment with ACE-I/ARB and/or calcium channel blockers (CCB) over a period of 10 years. Patients were stratified according to their blood pressure 1 year after transplantation [controlled (≤130/80 mmHg; CTR, 181 patients) and noncontrolled (>130/80 mmHg; non-CTR, 324 patients)] and according to antihypertensive treatment (ACE-I/ARB and/or CCB taken for at least 2 years). One year after transplantation, 88.4% of CTR and 96.6% of non-CTR received antihypertensive treatment ( P  < 0.05). Graft survival was longer in CTR than in non-CTR ( P  < 0.05). Importantly, graft survival was longer in patients who received long-term treatment with ACEI/ARB, CCB, or a combination of ACEI/ARB and CCB ( P  < 0.001). The beneficial effect of ACEI/ARB therapy was more pronounced in non-CTR compared with that of CTR. We conclude that blood pressure control is a key target for long-term graft survival in renal transplant patients. Long-term ACEI/ARB and CCB therapy is beneficial for graft survival, especially in patients with diabetes and/or albuminuria.     

Patient characteristics rather than the type of dialyser predict the variability of endothelial derived surface molecules in chronic haemodialysis patients.

BACKGROUND: Cardiovascular disease (CVD) is a frequent complication in chronic haemodialysis (HD) patients. Endothelial dysfunction, as measured by soluble cellular adhesion molecules (sCAM) and von Willebrand factor (vWf) in plasma, is an early manifestation of CVD. Today, it is unknown if, and to what extent, their levels are influenced by the type of dialyser. METHODS: Four dialysers, low-flux cuprammonium (CU); high-flux and low-flux polysulfone and super-flux polyethersulfone, were compared in 15 chronic HD patients in a randomized cross-over fashion. sCAM and vWf were measured at baseline as well as after 4 weeks, and both intra-dialytical and after 24 h (t24 h). Twenty healthy subjects served as controls. RESULTS: Baseline levels were considerably higher in chronic HD patients than in controls (soluble intercellular adhesion molecule-1: sICAM-1 732+/-216 vs 572+/-259 ng/ml, P = 0.06; soluble vascular cell adhesion molecule-1: sVCAM-1 1917+/-492 vs 1126+/-338 ng/ml, P<0.001; vWF: 205+/-55% vs 98+/-52%, P<0.001). After 4 weeks, no changes were observed. During and after HD, sCAM did not change, except in the case of CU (sICAM-1: 719+/-259 to 772+/-261 ng/ml, P = 0.04). CU induced a rise in vWF directly after HD (t4 h; from 188+/-48% to 255+/-92%, P<0.01), whereas all modalities induced a significant increase at t24 h (mean 228+/-54%, P = 0.02). The levels of sCAM and vWf appeared to be dependent on the individual patients rather than on the type of dialyser (explained variance by different patients: 66%-91%, P<0.001; by type of dialyser 0.4-1.2%). CONCLUSIONS: Baseline levels of sCAM and vWf were markedly higher in chronic HD patients than in controls and did not change after 4 weeks with any dialyser. All membranes induced a marked rise in vWf at t24 h, whereas sICAM-1 increased only in the case of CU at t4 h. As sCAM showed no marked changes during HD with any other modality, our study suggests activation of blood cells rather than endothelial cells. As pre-dialysis levels of sCAM and vWf varied noticeably between individual patients, endothelial dysfunction seems to be far more dependent on patient-related factors than on the HD treatment itself.     

Calcium channel blocker use and mortality among patients with end-stage renal disease

BACKGROUND: Patients on dialysis suffer from alarming rates of cardiovascular disease. While calcium channel blockers (CCBs) are prescribed widely to patients with end-stage renal disease (ESRD) for the treatment of hypertension, the long-term outcomes associated with the use of these medications are not known. We sought to determine the association between CCB use and mortality among a cohort of ESRD patients. METHODS: Data were utilized from the United States Renal Data System Dialysis Morbidity and Mortality Wave II, a randomly selected prospective cohort of 4065 ESRD patients who began dialysis in 1996. Clinical data, including medication information, were collected 60 days after the start of dialysis. Subsequent survival status and cause of death were ascertained. The Cox proportional hazards model was used to estimate the relative risk of death associated with CCB use. RESULTS: Data from 3716 patients (91.4%) were available for analysis. Fifty-one percent of the study patients were prescribed a CCB. The use of a CCB was associated with a 21% lower risk of total mortality (RR 0.79, CI 0.69 to 0.90) and a 26% lower risk of cardiovascular specific mortality (RR 0.74, CI 0.60 to 0.91). For patients with pre-existing cardiovascular disease, CCB use was associated with a 23% (RR 0.77, CI 0.65 to 0.91) and 32% (RR 0.68, CI 0.53 to 0.87) lower risk of total and cardiovascular mortality, respectively. CONCLUSION: After controlling for known risk factors and potential confounders, CCBs were found to be associated with a lower risk of mortality among ESRD patients.