Cytokine release and serum lipoprotein (a) alterations during hemodialysis

It has been reported recently that a number of cytokines, mainly tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6, can alter lipid metabolism and produce hyperlipidemia. Studies in hemodialysis (HD) patients have demonstrated increased production of these cytokines during HD. In order to investigate any possible relationship between changes of cytokines and lipid concentrations during HD in the serum of 25 uremic patients on chronic HD using modified cellulose membranes, TNFalpha, IL-1beta, IL-6, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein a (Lp[a]), and total proteins were measured immediately before (pre-HD) and after HD (post-HD), in one session. The post-HD values were corrected according to the hemoconcentration based on the changes in serum total proteins. Serum TNFalpha and IL-1beta levels were significantly increased from 38.24 +/- 17.85 pg/ml and 2. 60 +/- 3.64 pg/ml pre-HD to 48.86 +/- 25.21 and 3.49 +/- 4.08 pg/ml post-HD, p < 0.001 and p < 0.05 respectively. Also Lp(a) levels presented a statistically significant increase post-HD and were almost doubled (pre-HD: 15.41 mg/dl, to post-HD: 27.39 mg/dl, p < 0. 05). Serum IL-6 as well as serum TC, TG, HDL-C, and LDL-C did not show any statistically significant alterations during HD. A significant positive correlation was detected between TNFalpha and Lp(a) values post-HD (r: 0.413, p: 0.04), but not between pre-HD values. No further relationship between serum cytokines and the other estimated lipid parameters was observed, either between pre- or post-HD values. Our results indicate that release of TNFalpha and IL-1beta during HD have no effect on serum lipids concentration, except on Lp(a). It seems that the acute rise of this lipoprotein during hemodialysis may be related with the TNFalpha overproduction.     

Effect of dialysis type on serum lipids, apolipoproteins, and lipoproteins

AIM: Dyslipidemia is common among patients with end-stage renal disease, whether treated by hemodialysis (HD) or peritoneal dialysis (PD). However, there are not enough data about the effect of dialysis type on serum lipoprotein (a) [Lp(a)], apolipoprotein (a) [Apo(a)], apolipoprotein (b) [Apo(b)], and lipid levels. The aim of this study was to determine the effect of dialysis type on serum lipid levels. MATERIALS AND METHODS: This study enrolled 40 HD patients (20 men and 20 women, aged 48.1 +/- 17.6 years) and 69 PD patients (35 men and 34 women, aged 45.2 +/- 16.3 years). Serum lipid profile including total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglyceride (TG), Apo(a), Apo(b), and Lp(a) were determined in HD and PD patients. Patients who have used statins within the last six months were not included in the study. RESULTS: No significant differences in TC, LDL-C, HDL-C, TG, Apo(a), Apo(b), or Lp(a) serum levels were found between HD and PD patients. Serum TC, LDL-C, HDL-C, TG, Apo(a), Apo(b), and Lp(a) in HD and PD patients were 172.2 +/- 42.7 (mg/dL) vs. 181.0 +/- 53.0 (mg/dL), 97.2 +/- 36.2 (mg/dL) vs. 101.4 +/- 33.6 (mg/dL), 45.3 +/- 11.9 (mg/dL) vs. 41.4 +/- 11.1 (mg/dL), 144.7 +/- 71.8 (mg/dL) vs. 173.0 +/- 76.8 (mg/dL), 1.2 +/- 0.5 (g/L) vs. 1.0 +/- 0.2 (g/L), 0.9 +/- 0.3 (g/L) vs. 1.2 +/- 0.3 (g/L), and 43.1 +/- 40.6 (mg/dL) vs. 46.0 +/- 42.7 (mg/dL), respectively. CONCLUSION: The results of this study show that the maintenance CAPD treatment is associated with more pronounced alterations of the lipoproteins and lipid metabolism than those observed during HD treatment.     

The role of heparin in the changes of lipid patterns during a single hemodialysis

The effects of heparin administered during dialysis on serum lipids and lipoproteins were evaluated by comparing dialysis with heparin and dialysis without heparin. Gabexate mesilate (GM), a synthetic proteinase inhibitor, was used as an anticoagulant during dialysis without heparin. In dialysis with heparin, significant increases were observed in free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), and plasma lipolytic activity (PLA). Triglyceride (TG) was decreased reciprocally and the lipoprotein electrophoretic pattern was markedly modified. In contrast, in dialysis without heparin, no significant changes were observed in all parameters of lipid metabolism. These data suggest that dialysis induced changes in lipids are mainly caused by heparin and that acetate and glucose in dialyzate make an almost negligible contribution to abnormal lipid patterns in patients on maintenance hemodialysis.     

The impact of haemodialysis-associated variables on lipid profile in Egyptian haemodialysis population

Introduction Haemodialysis (HD) patients appear to have particular susceptibility for cardiovascular (CV) diseases with lipid abnormalities among its significant contributors. However, there is controversy concerning the combined effect on lipid constituents during HD of the three commonly used variables; the type of heparin, dialysis membrane and the constituent of dialysate buffer bases. Consequently, this controlled prospective study was thought of. Patients Randomly 63 patients were assigned from Urology and Nephrology haemodialysis (HD) unit, Mansoura, Egypt for the planned study. Their mean age was 45.79 ± 13.11 years. Fourteen patients with end-stage renal disease (ESRD) served as control group for the remaining 49 HD patients. They were subdivided according to the HD duration (< and > 1 year), anticoagulant used (unfractionated [UFH] and low-molecular weight heparin [LMWH, Enoxaparin), membrane type (Hemophane [HP] and polysulfone [PS] membrane) and dialysate buffer bases (bicarbonate versus acetate based). Methods Determining the fasting lipid value of total cholesterol (TC) and triglycerides (TG) as well as lipoproteins including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and lipoprotein (a) [Lp (a)] was completed. Results Bicarbonate dialysate was associated with significantly lower TG (134.7 ± 11 mg/dl vs. 153 ± 14 mg/dl, p = 0.004), higher HDL-C (33.1 ± 3 vs. 28.3 ± 2, p = 0.0002) and subsequently better atherosclerosis risk ratio [TC/HDL-C (ARR)] (6.02 ± 0.09 vs. 5.3 ± 0.9, p = 0.001) despite its insignificant effect on TC and LDL-C. However, logarithm (log) Lp (a) level was significantly higher (1.92 ± 0.05 vs. 1.82 ± 0.04 p = 0.001) in comparison with acetate dialysate. Membrane type was not influential in those dialyzed for < 1 year before intervention while after a year of HD, PS (n = 11) compared to HP filters (n = 11) significantly lowered TC (151.7 ± 16 vs. 172.6 ± 12, p = 0.003), TG (127.8 ± 15 vs. 155.7 ± 15, p = 0.004), LDL-C (122.1 ± 5 vs. 130.6 ± 7, p = 0.006) levels as well as ARR (5.9 ± 0.5 vs. 5.4 ± 0.3, p = 0.02). Likewise was the reduction in log Lp (a) (1.9 ± 0.03 vs. 1.8 ± 0.04, p = 0.002) with insignificant effect on HDL-C. After 6 months, Enoxaparin caused significant improvement of TC (0.0004), TG (p = 0.018), LDL-C (p = 0.006), HDL-C (0.041) and Lp (a) (0.047) compared to UFH. Patients who continued on Enoxaparin for 3 more months displayed an even better attenuation in most of lipid parameters whilst continuation of UFH was insignificant. Switching few patients (n = 4) from UFH to LMWH for 3 months resulted in significant lowering of TC (153 ± 7 vs. 177.7 ± 3, p = 0.01), TG (127.5 ± 5 vs. 137.3 ± 4, p = 0.03) and LDL-C (124.7 ± 5 vs. 127.5 ± 5, p = 0.005). However, switching equal number of patients from LMWH to UFH caused no significant change. Conclusion Dyslipidaemia in Egyptian haemodialysis patients was improved when bicarbonate-based haemodialysis, the use of polysulfone membrane, and more so when the low-molecular weight heparin Enoxaparin were used.     

Alteration of the lipid and apolipoprotein contents of lipoprotein (a) in haemodialysis patients

BACKGROUND: To examine the possible alteration in Lp(a) composition, proteinand lipid contents of Lp(a) were determined in 10 haemodialysispatients (HD) matched with 10 controls (C) fox apo(a) phenotypes. METHODS: All subjects (HD and C) had Lp(a) concentrations greater than30 mg/dl (mean±SD : 82.3±41.4 vs 49.3±22.5mg/dl), a concentration which has been determined to be associatedwith an elevated cardiovascular risk. Apo(a)-containing particleswere isolated by immunoaffinity chromatography using a monoclonalanti-apo(a) antibody. RESULTS: The molar concentrations of lipid and protein constituents ofimmunoaffinity isolated Lp(a) were expressed as number of molesper mole of apo(a). Lp(a) from HD patients were significantlyricher in apo Clll (P<0.05) and triglycerides (TG) (P<0.05),compared to those of controls. Molar ratios of apo B, apo E,cholesterol and phospholipids per apo(a)-containing particleswere in the same range in both groups. CONCLUSIONS: Lp(a) from HD patients is characterized by an elevated contentin TG and apo Clll in comparison with those of controls. Furtherstudies are needed to evaluate in HD patients the contributionof changes in Lp(a) composition towards the metabolism of theseparticles.     

Lipoprotein abnormalities in hemodialysis and continuous ambulatory peritoneal dialysis patients

Lipid abnormalities are important variables in the development of vascular atherosclerotic lesions in ESRD patients while Lp(a) represents an independent risk factor. In order to evaluate lipid changes in HD and CAPD patients, serum cholesterol (TC), HDLc, LDLc, TG, apolipoproteins (AI,AII,B,E), Lp(a), and albumin levels were estimated in 109 ESRD dialyzed patients, 46 in HD and 63 in CAPD (mean duration 50 +/- 40 and 25 +/- 19 months, respectively), and 45 volunteers with high serum levels of C and TG, without renal insufficiency. Both HD and PD group revealed statistically significantly higher levels than controls for TC, TG, LDL-C, Apo-B,-E, while HDL-C levels were significantly lower. Except for the lower serum albumin levels in both dialyzed groups after six months lower ApoAI levels and higher ApoB levels were observed in HD and PD patients respectively. Lp(a) levels remained unchanged in HD group, while a statistically significant increase appeared in PD patients that was negative correlated with the decreased serum albumin levels. These results indicate that renal replacement modalities result in a different effect in lipoprotein metabolism that may play an important role in atherosclerotic vascular disease of dialyzed ESRD patients.     

Effect of Dialysis Type on Serum Lipids,Apolipoproteins, and Lipoproteins

Aim. Dyslipidemia is common among patients with end-stage renal disease, whether treated by hemodialysis (HD) or peritoneal dialysis (PD). However, there are not enough data about the effect of dialysis type on serum lipoprotein (a) [Lp(a)], apolipoprotein (a) [Apo(a)], apolipoprotein (b) [Apo(b)], and lipid levels. The aim of this study was to determine the effect of dialysis type on serum lipid levels. Materials and Methods. This study enrolled 40 HD patients (20 men and 20 women, aged 48.1?±?17.6 years) and 69 PD patients (35 men and 34 women, aged 45.2?±?16.3 years). Serum lipid profile including total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglyceride (TG), Apo(a), Apo(b), and Lp(a) were determined in HD and PD patients. Patients who have used statins within the last six months were not included in the study. Results. No significant differences in TC, LDL-C, HDL-C, TG, Apo(a), Apo(b), or Lp(a) serum levels were found between HD and PD patients. Serum TC, LDL-C, HDL-C, TG, Apo(a), Apo(b), and Lp(a) in HD and PD patients were 172.2?±?42.7 (mg/dL) vs. 181.0?±?53.0 (mg/dL), 97.2?±?36.2 (mg/dL) vs. 101.4?±?33.6 (mg/dL), 45.3?±?11.9 (mg/dL) vs. 41.4?±?11.1 (mg/dL), 144.7?±?71.8 (mg/dL) vs. 173.0?±?76.8 (mg/dL), 1.2?±?0.5 (g/L) vs. 1.0?±?0.2 (g/L), 0.9?±?0.3 (g/L) vs. 1.2?±?0.3 (g/L), and 43.1?±?40.6 (mg/dL) vs. 46.0?±?42.7 (mg/dL), respectively. Conclusion. The results of this study show that the maintenance CAPD treatment is associated with more pronounced alterations of the lipoproteins and lipid metabolism than those observed during HD treatment.     

Cardiovascular Risk Factors in Non-Diabetic Hemodialysis Patients: A Comparative Study

Patients on hemodialysis (HD) are prone to atherosclerotic cardiovascular complications. In an attempt to determine the significance of several atherosclerotic and thrombogenic parameters as risk factors for atherothrombotic cardiovascular disease (CVD) in these patients, we compared two groups of non-diabetic HD patients matched for age and sex, selected according to the absence (group 1, n?=?30) or presence (group 2, n?=?30) of symptomatic atherothrombotic vascular disease affecting the coronary, cerebral, or peripheral arteries. Duration of HD, primary renal disease (PRD), presence of hypertension, EPO treatment, and smoking habits were recorded. Serum total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, TC/HDL-C ratio, lipoprotein(a) (Lp(a)), fibrinogen (FG), plasminogen (PLG), fibronectin (FN), and hematocrit (HCT) were measured pre-HD in a midweek session. The same blood parameters were also assessed in twenty matched clinically healthy subjects (controls). None of the blood parameters differed between groups 1 and 2, except for serum Lp(a) and FN, which were higher in group 2 (p?=?0.005 and p?=?0.041, respectively). Both groups were not different regarding PRD, duration of HD, and EPO treatment, but the presence of hypertension and smoking habits were more common in group 2 (p?=?0.008 and p?=?0.045, respectively). Moreover, multiple stepwise logistic regression analysis with Lp(a), FN, hypertension, and smoking showed that the presence of hypertension (p?=?0.016) and the Lp(a) (p?=?0.027) and FN (p?=?0.024) levels, but not smoking, were independent predictors for the presence of atherothrombotic CVD. Our results suggest that hypertension, abnormal lipid particles, and thrombogenic proteins may contribute to the high prevalence of CVD in HD patients.     

Is arterial hypertension an underlying factor in the increased serum Lp(a) levels in ESRD dialyzed patients?

Except for the disorders in lipoprotein metabolism several other factors have been involved in the development of atherosclerotic changes in ESRD patients, including arterial hypertension. Serum lipid profile (total cholesterol (TC), triglycerides (TG), apolipoproteins (AI,AII,B,E) and Lp(a)) was evaluated in 109 ESRD dialyzed patients, 46 in HD and 63 in CAPD and 45 hyperlipidemic patients without renal failure (HL-group). According to the presence of arterial hypertension the dialyzed patients were divided in two groups: group A of 42 hypertensive patients, (mean age 62.3 +/- 15.5 years), which were satisfactorily controlled with anti-hypertensive medication, and group B of 67 non-hypertensive patients, (mean age 66.6 +/- 11.9 years). Lp(a) levels were statistically significantly higher than HL group in both HD (p = 0.001) and PD (p < 0.05) patients. Besides, by dividing HD and PD group in hypertensive and non-hypertensive patients, Lp(a) levels were statistically significantly higher in hypertensive patients, while such a difference was not observed among non-renal failure patients. These results indicate that arterial hypertension may play an important role in Lp(a) serum titles, in ESRD patients undergoing either HD or PD.     

Elevated Hepatocyte Growth Factor Levels at the Beginning of High-Flux Hemodialysis Are Due to Heparin Administration

Background. It has been reported that hemodialysis (HD) stimulates hepatocyte growth factor (HGF) release, but it is not clear if this stimulation is due to HD itself or to heparin used during HD. To clarify this issue, we undertook the present study. Methods. We studied 18 HD patients using high-flux dialyzers, during a single 4-hr hemodialysis session (session A). The dialyzers were pre-rinse with normal saline without heparin, and HD was started with zero ultrafiltration and without anticoagulation. Anticoagulation was administered as IV injection (80 IU/kg of LMWH enoxaparin sodium) 10 min after the beginning of HD. HD was continued for 10 more minutes and then as prescribed. HGF serum levels were measured before the beginning of the HD session (sample t0) as well as 10 and 20 minutes after the beginning of the session (samples t10 and t20). In six more patients (controls), the same study was repeated but without the administration of LMWH during the first 20 min of HD initiation (session B). Results. In comparison with t0, t10 HGF serum levels changed significantly in neither session A nor in session B. However, at t20, HGF levels increased significantly in session A compared with t0 (increment 666.3 ± 211.0%, p < 0.0001) and t10 (increment 894.2 ± 506.0%, p < 0.0001), but not in session B. No differences were found between sessions A and B at samples t0 and t10 (p?=?NS). HGF serum levels at t20 in session A were found to be higher compared with corresponding levels in session B (p < 0.0001). Conclusion. Elevated HGF serum levels at the beginning of high-flux HD session are due to LMWH administration.     

Effect of hemodiafiltration on pregnancy-associated plasma protein A (PAPP-A) and related parameters

BACKGROUND: Dialysis patients are at high risk of vascular/cardiovascular complications with multifactorial pathogenesis, and pregnancy-associated plasma protein A (PAPP-A) is one of the new markers related to cardiovascular risk. Because hemodiafiltration (HDF) is supposed to be better for cardiovascular status, the aim of this study was to describe whether it has any advantage concerning changes of PAPP-A and related molecules during the session in comparison with hemodialysis (HD). METHODS: The studied group consisted of 20 chronic hemodialysis patients. In each patient, PAPP-A and related parameters-IGFBP-4 (insulin like growth factor binding protein), IGF-I (insulin like growth factor), and two MMPs (matrix metalloproteinases)-2 and 9-were determined both during a single online HDF session (high-flux polysulfone membrane HF80, postdilution) and during a single HD session (low-flux polysulfone membrane F6, F7) at time 0 (start), 15 min, 120 min, and 240 min (end) of the session. RESULTS: PAPP-A, elevated at baseline in dialysis patients, changes significantly both during HDF and HD without significant differences between these two procedures (mean levels during HDF were 24.3, 53.9, 24.3, and 27.3 mIU/L). It increases more than two-fold from 0 to 15 min of the session (p < 0.001) and then decreases until the end of the session (p < 0.001). MMP-2 decreased slightly during both sessions (p < 0.001), and changes of other molecules were only minimal. CONCLUSION: A single HDF session compared to HD has no advantage in the decrease of PAPP-A and other tested molecules, all of them related to cardiovascular risk. Studies aimed at a long-term effect of both procedures on these parameters would be needed to further evaluate these therapeutical strategies.     

Inflammation as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis in haemodialysis patients: the role of chlamydia and cytomegalovirus infection

OBJECTIVES: Atherosclerotic vascular disease is the most frequent complication seen in haemodialysis (HD) patients. Evidence suggests that inflammation may play a role in the pathogenesis and progression of atherosclerosis. Our aim was to evaluate the causative role of inflammation in atherosclerosis among HD patients. METHODS: Intima-media thickness (IMT) in carotid arteries was determined in 54 HD patients and 52 controls. Plasma levels of lipids, glucose, albumin and several acute phase proteins, and immunoglobulin G titres against chlamydia and cytomegalovirus were measured in all subjects. RESULTS: Mean carotid IMT was significantly greater in HD patients than in controls (0.75 mm vs 0.56 mm, P < 0.005). While plasma levels of C-reactive protein (CRP), serum amyloid A (SAA), lipoprotein (a) Lp(a), fibrinogen and ferritin were higher in HD patients, albumin levels were lower. In HD patients, carotid IMT was correlated positively with CRP (R = 0.29, P = 0.019), SAA (R = 0.69, P < 0.001), Lp(a) (R = 0.42, P = 0.001), fibrinogen (R = 0.57, P < 0.001) and chlamydia pneumonia immunoglobulin G titres (R = 0.50, P < 0.001), and negatively with albumin levels (R = -0.33, P = 0.02); there was no relationship between carotid IMT and hypertension, plasma lipid levels and cytomegalovirus. In multivariate regression analysis, these variables still showed a significant relationship with IMT (R(2) = 0.694 and P < 0.001). CONCLUSION: We conclude that atherosclerotic changes are more common in HD patients than in controls, and that inflammatory processes may play a role in the pathogenesis of atherosclerosis.     

Heat shock proteins in children and young adults on chronic hemodialysis

Chronic inflammation, lipid and autoimmune disorders are hallmarks of atherogenesis, and hemodialysis per se may be an additional factor predisposing to accelerated atherosclerosis. Elevated levels of heat shock proteins (HSP) and antibodies against these HSP have been described in adults with atherosclerotic lesions and cardiovascular events, but to date there has been a scarcity of investigations on these parameters in adult and pediatric patients on hemodialysis (HD). We have investigated the HSP profile in hemodialyzed children and the impact of a single HD session on those proteins and their correlations with known risk factors for atherosclerosis. The study group consisted of 17 children and young adults undergoing HD with polysulfone membranes. The control group comprised 15 age-matched subjects with normal kidney function. The serum concentrations of Hsp60, Hsp90alpha, anti-Hsp60, anti-Hsp70, and sE-selectin were assessed by an enzyme-linked immunosorbent assay, and serum concentration of high-sensitivity-C-reactive protein was assayed by nephelometry. The serum lipid profile [total cholesterol (CHOL), high-density lipoprotein-CHOL, low-density lipoprotein-CHOL, triglycerides] was also estimated. Compared to the control values, the median values of Hsp60 before the HD session were lower, whereas those of Hsp90alpha and anti-Hsp60 were higher. A single HD session raised the median values of Hsp60 and Hsp90alpha and decreased the concentrations of anti-Hsp60 and anti-Hsp70. In addition, the concentrations of HSPs and the antibodies against them correlated with the lipid markers both before and after HD. The altered HSP and anti-HSP concentrations in HD children, which correlated with the lipid profile and the endothelial markers, suggest a dysfunctional HSP system in this population and the possibility of HSPs being classified as new markers of atherosclerosis.     

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.     

Body mass index and cardiovascular risk factors and biomarkers in hemodialysis patients

BACKGROUND: Being overweight and obesity are associated with improved survival in hemodialysis (HD) patients, based on mechanisms that are presently uncertain. We compared traditional and uremia-related cardiovascular risk factors in HD patients stratified according to their body mass index (BMI). METHODS: One hundred sixteen HD patients were stratified into 4 groups according to the BMI: underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9) and obese (> or =30). Blood samples were obtained before the HD session to measure serum albumin, high-sensitivity C-reactive protein, fibrinogen, ferritin, total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein A-I and apolipoprotein B-100, apolipoprotein B (apoB) to apolipoprotein A (apoA) ratio and Lp(a) lipoprotein. RESULTS: There were 3 underweight (excluded from the analysis), 58 normal weight, 35 overweight and 20 obese patients. Their mean age was 62.1 +/- 14.1 years. There were 68 men and 45 women. Mean dialytic age was 5.32 +/- 3.2 years. The mean BMI of the study population was 25.2 +/- 4.1. The prevalence of smoking habit was similar in the 3 groups (17.2%, 8.5% and 25%, respectively; p=0.28). The prevalence of hypertension was higher in overweight (77.1%) and obese (65%) patients than in leaner counterparts (53.4%), although the difference was not significant. Conversely, diabetes prevalence was significantly higher in overweight and obese patients (22.8% and 30%, respectively) than in normal weight patients (6.9%; p=0.02). The serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, Lp(a) lipoprotein, apolipoprotein A-I, apolipoprotein B-100, and apoA/apoB ratio were similar in the 3 BMI groups. Triglycerides levels were significantly higher in obese (221.2 +/- 132.7 mg/dL) and overweight (230.5 +/- 119.3 mg/dL) patients than in those of normal weight (154.6 +/- 78.8 mg/dL; p=0.02). Most of the uremia-related cardiovascular risk factors (anemia, hyperparathyroidism, chronic inflammation) were comparable among BMI categories as well as the levels of C-reactive protein, fibrinogen and ferritin. CONCLUSION: The present study suggests that almost all traditional and uremia-related cardiovascular risk factors do not differ significantly among different categories of BMI in hemodialysis patients.     

Inflammatory markers and platelet aggregation tests as predictors of hemoglobin and endogenous erythropoietin levels in hemodialysis patients

BACKGROUND/AIMS: Chronic inflammation is a common cause of severe anemia and hyporesponsiveness to recombinant erythropoietin (EPO) therapy in maintenance hemodialysis (HD) patients. We compared various acute-phase markers and ex vivo platelet aggregation tests in relation to clinical conditions in order to find factors predictive of hemoglobin (Hb) and endogenous EPO levels in a cross-section of clinically stable HD patients. METHODS: In 100 subjects, pre-HD blood levels of C-reactive protein (CRP), alpha(1)-acid-glycoprotein (AGP), alpha(1)-antitrypsin (AT), immunoglobulin (Ig) M and G (by nephelometry), antigens of endothelial von Willebrand factor (vWF), type 1 plasminogen activator inhibitor and thrombomodulin, interleukin-6, lipoprotein(a) [Lp(a)] and EPO (by ELISA), and albumin, fibrinogen, iron metabolism indices, thyroid-stimulating hormone, phosphorus, parathormone, total cholesterol, triglycerides, viral hepatitis B/C markers, liver enzyme, and aluminium were determined. Platelet aggregations in response to ristocetin (RIPA), adenosine diphosphate, and collagen were measured in whole blood (electric impedance method) and platelet-rich plasma (optical aggregometry). RESULTS: Hb levels inversely correlated with IgM, Lp(a), soluble vWF antigen, phosphorus, and all platelet aggregations in whole blood, but not in platelet-rich plasma. HD duration and triglycerides were positive correlates of anemia. In a multivariable analysis, increased IgM, short HD duration, increased Lp(a) and enhanced whole blood RIPA (in descending order of significance) were independent predictors of low Hb levels. In 51 patients not treated with recombinant EPO, serum levels of this hormone inversely correlated with whole blood RIPA, AT, age, vWF antigen, AGP, and positively with viral hepatitis marker. Anemia and EPO levels were not affected by gender, body mass index, cause of renal failure, residual renal function, HD dose, protein catabolic rate, use of different heparins or dialysate buffers, ACE inhibitor therapy, and parathyroid or thyroid function. In additional 10 patients, single HD session resulted in an increase in IgM levels associated with a fall in total lymphocyte counts. CONCLUSION: Subclinical inflammation is an important determinant of anemia in maintenance HD patients. Increased serum IgM reflecting a microinflammatory effect of HD procedures, enhanced whole blood RIPA as a surrogate of vascular endothelial damage, and Lp(a) as its promoter could be markers of such impaired erythropoiesis.     

低分子肝素对血液透析患者脂质代谢影响的临床研究

目的 探讨长期应用低分子肝素抗凝对尿毒症血液透析患者脂质代谢的影响。方法 采用为期１年的长期开放、随机对照的方法,选择３５例无明显出血倾向尿毒症患者,随机分成普通肝素（ＵＦＨ）组（１３例）及低分子肝素（ＬＭＷＨ）组（２２）例,于透前分别按个体剂量给予普通肝素及低分子肝素钠动脉血路端注射,并在治疗前、治疗后６月及１２月检测血脂、脂蛋白、载脂蛋白水平及脂酶活性。结果 （１）两治疗组透析前血甘油三酯（Ｔ     

Impact of membrane choice and blood flow pattern on coagulation and heparin requirement - potential consequences on lipid concentrations

Background: We reasoned that procoagulant activity, and by implication heparin requirement, during haemodialysis are influenced, amongst other factors, by the type of membranes and the geometry of the blood line system. In addition, there are indications that heparin has dose-dependent effects on the lipid status of chronic haemodialysis patients. Methods: In a parallel group design we compared patients treated with cuprophane (CU) and polycarbonate-polyether (PC-PE) plate dialysers. In both groups, blood line geometry was varied by including in a first phase and omitting in a second phase drip chambers in the arterial blood line. End-points were changes in coagulation parameters, i.e. thrombin-antithrombin III complex (TAT), plasmin-anti-plasmin complex (PAP), and prothrombin fragment (F1+2) concentrations measured by sandwich ELISA. Subsequently all patients were switched to PC-PE dialysers for 6 months and the heparin dose was reduced in a stepwise fashion. Lipid levels and coagulation parameters were monitored. Finally, in an ancillary study, the correlation between heparin dose and LDL/HDL ratio was assessed in patients chronically exposed to PC-PE membranes and low doses of heparin. Results: Post-dialytic concentrations of coagulation and fibrinolysis parameters were significantly lower in the PC-PE group (TAT 21.0±4.4 &mgr;g/l; PAP 1180±1148 &mgr;g/l; F1+2 4.2±0.4 nmol/l) compared to the CU group (TAT 57.3±10.8 &mgr;g/l; PAP 1789±185 &mgr;g/l; F1+2 8.8±1.0 nmol/l), independently of the use of an arterial drip chamber. Omission of the arterial drip chamber led to lower TAT in the CU group (42.2±5.8 &mgr;g/l, P <0.05), but not in the PC-PE group. In contrast, PA and F1+2 concentrations did not change significantly in either group. Down-titration of heparin dose (from 20.4±1.1 to (9.4±0.9 IU/kg/h) was associated with a significant decrease in serum triglycerides (from 2.9±0.9 to 2.0±0.6 mmol/l, P <0.05), LDL-cholesterol (from 3.4±0.2 to2.7±0.4 mmol/l, P <0.05) and LDL/HDL-ratio (from 3.2±0.3 to 2.0±0.3, P <0.05) with no significant change of total or HDL-cholesterol after 6 months. In an ancillary analysis, a correlation between lipid parameters (LDL/HDL ratio) and heparin dose was confirmed in 24 patients chronically exposed to PC-PE membranes (r=0.473, P <0.05). Conclusions: In a prospective exploratory study (I) heparin requirement is lower with the use of a polycarbonate-polyether membrane compared to a cuprophane membrane, (ii) heparin requirement is influenced by blood line geometry (decreased with omission of an arterial drip chamber), and (iii) in patients on polycarbonate-polyether membranes down-titration of heparin is associated with a reduction of serum triglycerides, LDL cholesterol, and LDL/HDL ratio. Our data suggest that reduction of heparin dose improved lipid profile. These preliminary observations require confirmation by parallel group controlled studies with controlled dietary intake.     

Effect of Hemodiafiltration on Pregnancy-Associated Plasma Protein A (PAPP-A) and Related Parameters

Background. Dialysis patients are at high risk of vascular/cardiovascular complications with multifactorial pathogenesis, and pregnancy-associated plasma protein A (PAPP-A) is one of the new markers related to cardiovascular risk. Because hemodiafiltration (HDF) is supposed to be better for cardiovascular status, the aim of this study was to describe whether it has any advantage concerning changes of PAPP-A and related molecules during the session in comparison with hemodialysis (HD). Methods. The studied group consisted of 20 chronic hemodialysis patients. In each patient, PAPP-A and related parameters—IGFBP-4 (insulin like growth factor binding protein), IGF-I (insulin like growth factor), and two MMPs (matrix metalloproteinases)-2 and 9—were determined both during a single online HDF session (high-flux polysulfone membrane HF80, postdilution) and during a single HD session (low-flux polysulfone membrane F6, F7) at time 0 (start), 15 min, 120 min, and 240 min (end) of the session. Results. PAPP-A, elevated at baseline in dialysis patients, changes significantly both during HDF and HD without significant differences between these two procedures (mean levels during HDF were 24.3, 53.9, 24.3, and 27.3 mIU/L). It increases more than two-fold from 0 to 15 min of the session (p < 0.001) and then decreases until the end of the session (p < 0.001). MMP-2 decreased slightly during both sessions (p < 0.001), and changes of other molecules were only minimal. Conclusion. A single HDF session compared to HD has no advantage in the decrease of PAPP-A and other tested molecules, all of them related to cardiovascular risk. Studies aimed at a long-term effect of both procedures on these parameters would be needed to further evaluate these therapeutical strategies.     

Course of serum lipoprotein(a) and acute phase protein levels in patients undergoing open heart surgery

BACKGROUND: Lipoprotein(a) [Lp(a)] is an important risk factor in the pathogenesis of coronary artery disease because of its thrombogenic and atherogenic properties. Lp(a) also displays another property by acting as an acute phase reactant. METHODS: In this work, the study group consisted of 20 male patients having coronary artery bypass under cardiopulmonary bypass (CPB). Preoperative and postoperative levels of plasma total cholesterol, triglyceride, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), alpha-1 antitrypsin (a1-AT), alpha-2 macroglobulin (alpha 2-MG), alpha-1 acid glycoprotein (alpha 1-AG), Lp(a) were measured in all patients one day before and after the 1st, 2nd, 4th, and 10th days of CPB. RESULTS: It was observed that the levels of Lp(a) levels gradually reached the preoperative levels at the 10th postoperative day period. Observed change of the Lp(a) levels was similar to that of the other acute phase proteins which are synthesized and released from liver. In contrast, alpha 2-MG has shown different behaviour in terms of operative values. The changes observed for all these 3 parameters were found to be statistically significant (p<0.01). CONCLUSIONS: The data has indicated that Lp(a) levels show similar progress with alpha 2-MG levels. It can be concluded that serum levels of Lp(a) after coronary arterial bypass decrease depending upon several factors and reach basal levels at the end of a 10 day-period of postoperation. The main cause for this decrease might result from the contact of blood with foreign surfaces of the heart-lung machine.