Association of age with muscle mass, fat mass and fat distribution in non-diabetic haemodialysis patients.

BACKGROUND: In the general population, aging induces changes in body composition, such as sarcopenia or a relative increase in visceral fat, but it remains unclear if similar changes occur in elderly haemodialysis (HD) patients. METHODS: Age-related changes in muscle and fat mass and fat distribution in the thigh and abdomen were cross-sectionally investigated in Japanese HD patients. The thigh muscle area (TMA), thigh intermuscular fat area (IMFA), thigh subcutaneous fat area (TSFA), abdominal muscle area (AMA), abdominal visceral fat area (AVFA) and abdominal subcutaneous fat area (ASFA) were measured by computed tomography in 134 non-diabetic patients between 21 and 82 years on HD. AMA, AVFA and ASFA were also measured in 70 age-matched controls. RESULTS: Muscle mass, fat mass and fat distribution differed significantly with age in both HD patients and controls, without significant differences in BMI. In both male and female HD patients, TMA and AMA showed significant negative correlations with age. All measures of subcutaneous fat-including TSFA, ASFA and the triceps skinfold thickness, were inversely associated with age in the female patients. In contrast, both IMFA and AVFA showed significant positive correlations with age in both male and female patients. The increase in the AVFA/ASFA ratio with age suggests progression of visceral fat accumulation in the elderly HD patients. Controls showed similar relationships between age and muscle mass and visceral fat accumulation. CONCLUSIONS: We found an association between age and decrease in muscle mass as well as increase in visceral and intermuscular fat in non-diabetic HD patients. Such changes may be associated with the metabolic abnormalities and increased mortality in elderly HD patients.     

Effect of erythropoietin on lipid profile in haemodialysis patients

Summary: Effect of recombinant human erythropoietin (rHuEPO) was determined on lipid levels (i.e. total cholesterol, triglycerides, high density lipoproteins [HDL], low density lipoproteins [LDL]) of 17 anaemic patients on maintenance haemodialysis. Estimations were done before initiating rHuEPO therapy and repeated 6 months later. There was an increase in haemoglobin (7.6 ± 1.09 to 10.9 ± 1.62 gm/dL, P < 0.001), and a significant decrease in total cholesterol (217 ± 22 to 196 ± 18 mg/dL, P < 0.001) and triglyceride levels (200 ± 20 to 186 ± 15 mg/dL, P < 0.001). There was no significant effect on HDL and LDL levels.     

Atherogenic lipid profile and lipoprotein(a) in relation to serum albumin in haemodialysis patients

Malnutrition in haemodialysis patients is associated with anincreased cardiovascular mortality. Lipoprotein(a) (Lp(a)) isan independent risk factor for atherosclerotic cardiovasculardisease. To evaluate the relationship between atherogenic lipidprofile and serum albumin in haemodialysis patients we measuredfasting serum Lp(a), total cholesterol (TC), high-density lipoprotein-cholesterol(HDL-C), triglyceride (TG), apoprotein A-I (ApoA-I), apoproteinB (ApoB) and albumin in 101 haemodialysis patients and in 46healthy subjects as a control. The haemodialysis patients weredivided into two groups on the basis of the level of serum albumin:group I, serum albumin <4.0 g/dl; group II, serum albumin>4.0 g/dl. Haemodialysis patients as a whole (n=101, 17.1 mg/dl (10.3–30.9))had higher serum Lp(a) than normal subjects (n = 46, 10.5 mg/dl(3.3–24)) (P<0.05). Lp(a) in group I (n = 38, 27.1mg/dl (14.6-35.0)) was significantly higher than in group II(n = 63, 14.5mg/dl(7.7–21.7), P<0.005) and normal subjects(P<0.0005). However, serum Lp(a) level of group II was notdifferent from those of normal subjects. There was a significantinverse correlation between serum Lp(a) and albumin concentration(r_s = -0.26, P<0.01). TC, TG, HDL-C, ApoA-I, ApoB, TC/HDL-C,and ApoA-I/ApoB ratios were not different between group I andgroup II. No correlation was found between albumin and TC, TG,HDL-C, TC/HDL-C, and ApoA-I/ApoB ratios. These results suggest that Lp(a) could be responsible for anincreased cardiovascular mortality in haemodialysis patientswith malnutrition.     

The significance of serum homocysteine levels in diabetic patients on haemodialysis.

BACKGROUND: Atherosclerotic diseases are the major cause of mortality and morbidity in patients on haemodialysis (HD). Furthermore, the prognosis of diabetic patients on HD is especially poor due to atherosclerotic complications. Because homocysteine (Hcy), a sulfur-containing amino acid, is emerging as an important risk factor for atherosclerosis in patients with end-stage renal disease, we examined the significance of serum Hcy levels in diabetic patients on HD. METHODS: We measured total serum Hcy levels (tHcy) in 31 patients with diabetes mellitus on HD (DM group) and 37 non-diabetic patients on HD (N group), adjusting for age and HD duration. Linear regression analysis was used to assess the correlation of multiple variables to tHcy. RESULTS: The proportion of atherosclerotic disease in the DM group was significantly higher than in the N group. However, serum tHcy, serum creatinine and per cent creatinine generation rate in the DM group were significantly lower than in the N group. In the DM group, serum tHcy was positively correlated with creatinine, albumin and per cent creatinine generation rate, respectively. This was not the case in the N group. CONCLUSIONS: The demethylation pathway in methionine metabolism in the liver, which is linked directly to the creatinine generation system, may be disturbed in diabetic patients on HD. This may be the reason why serum tHcy and creatinine in diabetic patients on HD are lower than in non-diabetic patients on HD. Therefore, it is necessary to consider the possibility of an altered relation between serum tHcy and vessel disease when evaluating the atherogenic risk in diabetic patients on HD.     

Coronary calcification and its association with mortality in haemodialysis patients

Aim:   Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality.
Methods:   A cross-sectional study was conducted in 59 haemodialysis patients. CaCs was assessed by multidetector-row computed tomography and stratified as: CaCs of less than 10 Agatston units (U), no calcification; CaCs of 10–400 U, mild-to-moderate; and CaCs of more than 400 U, severe calcification. The effects of age, haemodialysis duration and biochemical and inflammatory markers on CaCs logarithm were evaluated by multiple linear regression analysis. Cox regression analysis was used to measure the impact of CaCs of more than 400 on 2-year mortality.
Results:   Coronary calcifications were detected in 64.5% of patients, and the median of CaCs was 31.7 U (0–589.7) with a range of 0–5790.0 U. Twenty-one (35.5%) patients had mild-to-moderate and 17 (29%) severe CaCs. Patients with severe CaCs were older and showed a higher prevalence of ischaemic heart disease and a higher body mass index ( P  = 0.04). A trend towards higher C-reactive protein levels was found in patients with severe CaCs. Advanced age was the only variable that influenced CaCs logarithm independently. The effect of severe CaCs on 2-year mortality did not persist after adjustment for other covariates.
Conclusion:   Coronary calcification was highly prevalent in these uraemic patients on chronic haemodialysis. A correlation was evidenced between CaCs and advanced age, but severity of the CAC score did not have an impact on 2-year mortality of this cohort.     

Homocysteine and lipid peroxidation in haemodialysis: role of folinic acid and vitamin E.

BACKGROUND: Cardiovascular diseases are the leading cause of death in haemodialysis patients. Hyperhomocysteinaemia is an independent risk factor. Basic research has provided strong evidence that oxidation of low-density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis. Oxidative stress, lipid metabolism alterations, and hyperhomocysteinaemia observed in haemodialysis patients could induce increases in LDL oxidation. This study was designed to determine the effect of folinic acid on hyperhomocysteinaemia and to assess the antioxidant efficacy of folinic acid. The antioxidant effect of folinic acid was compared with that of vitamin E. METHODS: Sixteen stable patients (11 men, five women; mean age 54.3+/-6.32 years) on standard haemodialysis received 400 mg of vitamin E, orally, at the end of each haemodialysis session for 3 months. After a 1-month wash-out, they received 10 mg of folinic acid, intravenously, at the end of each haemodialysis session for an additional 3 months. Blood samples were drawn in the morning after an overnight fast and before dialysis. Plasma vitamin E was analysed by high-pressure liquid chromatography. Malondialdehyde (MDA) was determined using a fluorimetric method and plasma copper oxidized anti-LDL antibodies (Ab-LDLox) were measured with an ELISA method using native LDL and oxLDL as antigens. Plasma homocysteine was determined by an FPIA method. RESULTS: Folinic acid supplements significantly reduced hyperhomocysteinaemia (-44%), MDA concentrations (-40%), and IgG-LDLox titres (-13%). CONCLUSIONS: Treatment with folinic acid lowers plasma homocysteine levels and, like vitamin E, affords antioxidant protection, which prevents lipid peroxidation. This lowering of lipid peroxidation may reduce the risk of atherosclerosis and prevent or delay cardiovascular complications in HD patients.     

Possible involvement of increased glycoxidation and lipid peroxidation of elastin in atherogenesis in haemodialysis patients.

BACKGROUND: Glycoxidation and lipid peroxidation products accumulate in collagen of various tissues in haemodialysis patients with end-stage renal disease (ESRD). The purpose of this study was to test the hypothesis that increased glycoxidation and lipid peroxidation of aortic elastin is implicated in the cardiovascular complications, particularly atherosclerosis, of chronic haemodialysis patients. METHODS: Post-mortem aortic samples were obtained from 16 deceased subjects, including chronic haemodialysis patients (group 1 n=6, age 64.7+/-11.4 years) and control subjects (group 2 n=10, age 61.1+/-10.4 years). The samples were divided into three vessel wall sites: atherosclerotic intima, lesion-free intima, and media. They were sequentially treated with 0.01 M phosphate-buffered saline, collagenase, and elastase to obtain three fractions, namely soluble (SF), collagen (CF), and elastin (EF) fractions, respectively. Using spectrophotofluorometry, the pentosidine- and malondialdehyde (MDA)-linked fluorescence of these fractions was measured at wavelengths 335/385 and 390/460 (excitation/emission), respectively. RESULTS: Samples from haemodialysis patients (group 1) exhibited a significant increase in both pentosidine- and MDA-linked fluorescence of EF in atherosclerotic intima, lesion-free intima, and media samples, compared with samples from control subjects (group 2). In group 1, the levels of pentosidine- and MDA-linked fluorescence of EF were highest in atherosclerotic intima among the three aortic sites. Interestingly, in both groups, the levels of pentosidine- and MDA-linked fluorescence of EF were significantly higher than those of CF in all aortic sites. There was a strong correlation between the levels of pentosidine- and MDA-linked fluorescence in CF and EF for all aortic sites. In group 1, the pentosidine- and MDA-linked fluorescence levels of EF correlated significantly with the duration of haemodialysis in lesion-free intima and media. CONCLUSIONS: Our study provides the first biochemical evidence for a close link between aortic elastin glycoxidation and lipid peroxidation. In addition, we demonstrated high levels of these products in the aortic elastin of haemodialysis patients with ESRD. Our findings support the hypothesis that modification of aortic elastin by glycoxidation and lipid peroxidation may contribute to the development of vascular complications, particularly atherosclerosis, in patients with end-stage renal failure.     

Serum levels of beta-trace protein and its association to diuresis in haemodialysis patients.

BACKGROUND: Beta-trace protein (BTP) has been proposed as an alternative endogenous marker of the glomerular filtration rate. However, possible determinants of BTP in ESRD patients undergoing regular renal replacement therapy have not been evaluated. METHODS: Serum levels of BTP, beta-2-microglobulin, creatinine and urea were analysed before and after dialysis treatment in 73 patients [haemodialysis (HD) n=52; haemodiafiltration (HDF) n=21]. Patients were categorized into four groups with residual diuresis (RD)<0.5 l/day (group 1; n=24), 0.5-1 l/day (group 2; n=18), 1.1-1.5 l/day (group 3; n=12) and >1.5 l/day (group 4; n=19). Subsequently RD was compared to pre-treatment levels of BTP. RESULTS: HD treatment did not affect BTP serum levels [pre-treatment 8.1+/-4.1 mg/l (mean+SD) vs post-treatment 7.7+/-4.1 mg/l; -0.6 +/- 16.1%; ns]. However, in 6 out of 21 patients undergoing HDF BTP levels were reduced by more than 20%. Overall, the resulting decrease in serum concentration was minuscule (9.6+/-6.2 vs 8.3+/-4.9 mg/l; -14+/-21.9%; P=0.03). BTP serum levels were tightly associated to RD of the four groups. Comparison of BTP levels showed significant differences between patients of groups 1 vs 3 and 4 as well as 2 vs 4. CONCLUSIONS: BTP serum levels may serve as a surrogate marker for residual renal function since HD and HDF do not exert clinical relevant alterations on them. Furthermore, BTP serum concentrations appear strongly associated to RD.     

Circulating levels of ICAM-1, VCAM-1, and MCP-1 are increased in haemodialysis patients: association with inflammation, dyslipidaemia, and vascular events.

BACKGROUND: Increased levels of circulating adhesion molecules and chemokines have been reported in haemodialysis (HD) patients but the influence of the HD membranes on their secretion, as well as their pathophysiological implications, remains largely unknown. METHODS: Circulating levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) were measured by immunosorbent assay (ELISA) in 81 HD patients (45 male, mean age 57+/-13 years) and 35 normal subjects. All patients had been stabilized on renal replacement therapy for >3 months and were free of active infection. Thirty-three patients (40.7%) were routinely dialysed with modified cellulose membranes and 48 patients (59.3%) were dialysed with polysulfone membranes. Blood samples were taken directly from the arteriovenous fistula immediately before and at the end of a routine HD session. RESULTS: Pre-dialysis levels were significantly elevated in HD patients compared with controls (ICAM-1 515+/-177 vs 238+/-664 ng/ml, P<0.0001; VCAM-1 2107+/-648 vs 1012+/-115 ng/ml, P<0.0001; MCP-1 427+/-148 vs 125+/-42 pg/ml, P<0.0001). The HD session resulted in a significant increase in the levels of all three molecules measured (515+/-177 vs 679+/-187 ng/ml, P<0.0001; 2107+/-648 vs 2662+/-800 ng/ml, P<0.0001; 427+/-148 vs 567+/-153 pg/ml, P<0.0001, respectively). There was no difference in pre- or post-dialysis levels of the above molecules between patients routinely dialysed with either modified cellulose or polysulfone membranes. MCP-1 levels had a positive correlation with ICAM-1 levels (r=0.41, P<0.0005). VCAM-1 levels had a negative correlation with HDL levels (r=-0.30, P<0.01) and were significantly elevated in patients with HDL <35 mg/dl compared with patients with HDL > or = 35 mg/dl (2300+/-606 vs 1890+/-633 ng/ml, P<0.005). Log-transformed exact C-reactive protein (CRP) values were significantly correlated with ICAM-1 and VCAM-1 levels (r=0.41, P<0.005 and r=0.43, P<0.005, respectively). In addition, compared with patients with normal CRP values, patients with elevated CRP had significantly increased levels of ICAM-1 (466+/-166 vs 580+/-172 ng/ml, P<0.005). Patients with cardiovascular, cerebrovascular, or peripheral vascular diseases had significantly increased serum CRP and ICAM-1 levels compared with patients with no evidence of vascular disease (19.2+/-12.9 vs 7.9+/-11.8 mg/l, P<0.001 and 608+/-189 vs 474+/-155 ng/ml, P<0.005 respectively). CONCLUSIONS: Serum levels of ICAM-1, VCAM-1, and MCP-1 are increased in HD patients and probably result from either inadequate clearance or enhanced synthesis and release. HD session resulted in a significant increase of the above molecule levels but the exact mechanism(s) responsible for these alterations are yet to be fully elucidated. Increased levels of adhesion molecules are associated with inflammation, dyslipidaemia, and cardiovascular events. However, the potential link between these processes and its clinical significance warrants further investigation.     

Atherosclerosis in patients with analgesic nephropathy treated with haemodialysis

SUMMARY: Accelerated atherosclerosis was reported to be associated with chronic analgesic consumption, but most studies were retrospective, and individual findings have almost never been controlled with regard to other atherosclerotic risk factors. Ten haemodialysis patients with analgesic nephropathy (group I) and 19 haemodialysis patients where renal failure was not caused by analgesic nephropathy (group II) were included in the study. All patients were female without diabetes. Using B-mode ultrasonography, we compared intima-media thickness (IMT) in the carotid arteries and plaque occurrence, and their thickness in group I with that in group II. the possible differences in atherosclerotic risk factors in both groups were also investigated. In group I, the average age was 60.2 years, and the average dialysis treatment was 55.7 months. In group II, the average age was 54.6 years, and the average duration of dialysis treatment was 50.4 months. We found no statistically significant difference in the age and duration of dialysis treatment between groups I and II. the IMT values of the carotid arteries (0.97 vs 0.78 mm; P = 0.027) were significantly higher in group I. More patients had plaques in group I (90 vs 57.9%), and the number of plaques ( P = 0.037) and their thickness ( P = 0.043) were significantly higher in this group. There was no statistically significant difference in the atherosclerotic risk factors between groups I and II. the results indicate that patients with analgesic nephropathy treated with haemodialysis showed advanced atherosclerosis compared with other haemodialysis patients, despite no difference being found in the atherosclerotic risk factors between these patients.     

Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients.

BACKGROUND: Short-term studies have suggested that sevelamer hydrochloride, a non-aluminium- and non-calcium-containing hydrogel, is an effective phosphate binder in haemodialysis patients, and may produce favourable changes in the lipid profile. METHODS: To determine the long-term effectiveness of sevelamer hydrochloride, we performed an open-label clinical trial in 192 adult patients with end-stage renal disease on haemodialysis. Drug-related changes in the concentrations of serum phosphorus, calcium, calcium x phosphate product, parathyroid hormone, and low- and high-density lipoprotein cholesterol concentrations were the major outcomes of interest. RESULTS: Treatment with sevelamer was associated with a mean change in serum phosphorus of -0.71+/-0.77 mmol/l, serum calcium of 0. 08+/-0.22 mmol/l, and calcium x phosphate product of -1.46+/-1.78 mmol/l (P<0.0001 for all comparisons). There were no significant overall treatment-related changes in parathyroid hormone. Serum levels of LDL cholesterol decreased by 0.81+/-0.75 mmol/l (mean -30%, P<0.0001) and HDL cholesterol increased by a mean of 0.15+/-0.29 mmol/l (mean +18%, P<0.0001). Drug-related adverse events were infrequent and most were of mild intensity. CONCLUSION: Sevelamer is a safe and effective phosphate binder that leads to significant improvements in the calcium x phosphate product and lipid profile of haemodialysis patients.     

The role of oral dryness in interdialytic weight gain by diabetic and non-diabetic haemodialysis patients.

BACKGROUND: Factors influencing the percentage of daily interdialytic weight gain (IDWG%) and their interactions in haemodialysis (HD) patients have not been well-defined, especially in diabetic patients. We analysed contributing factors for the increase of IDWG%, particularly xerostomia (oral dryness), among diabetic and non-diabetic HD patients. METHODS: We collected 3 month prospective data in 184 stable HD patients (116 non-diabetic and 68 diabetic), including assessments of xerostomia by 100 mm visual analog scales (VASs), and the unstimulated whole salivary (UWS) flow rate was measured in 91 patients by a spitting method. RESULTS: Diabetic patients have higher IDWG% (P = 0.042) and VAS oral dryness score (P = 0.021), whereas, have lower UWS (P = 0.032). In non-diabetic patients, the VAS oral dryness score, age, Kt/V and blood urea nitrogen (BUN) level correlated independently with IDWG%. In diabetic patients, the haemoglobin A(1C) (HbA(IC)) correlated significantly with IDWG% after controlling for age, Kt/V and BUN level; however, when VAS oral dryness score was introduced into the regression model, the effect of HbA(IC) became marginally significant (P = 0.073) while the VAS oral dryness score became significantly correlated with IDWG%. The increases in IDWG% per unit change in VAS oral dryness score did not show significant difference between the non-diabetic and total diabetic patients; however, it was larger in patients with HbA(IC) >or=9%. CONCLUSIONS: Xerostomia plays a significant role in increasing IDWG% among diabetic and non-diabetic HD patients. In diabetic patients, the increased IDWG% associated with the increasing HbA(1C) level is largely dependent on the severity of xerostomia, and we speculate that insulin deficiency may operate synergistically with xerostomia in increasing IDWG% in patients with HbA(1C) >or=9%.     

A registry of haemodialysis patients and the progress of haemodialysis services in Lithuania.

Background. Until 1990, haemodialysis (HD) in Lithuania wasunderdeveloped, but after independence, development of HD started.Until 1996, no precise data about HD patients in Lithuania wereavailable. In order to create a registry of HD, we started tocollect data about dialysis services and HD patients in 1996.Every collection of data was followed by distribution and discussionof the results within the nephrological community. This studydescribes the changes of Lithuanian HD between 1996–2002. Methods. Between 1996 till 2002 all HD centres in Lithuaniawere annually visited and data were collected about all HD patients(response rate of 100%). The evaluation of the results duringour observational study was made according to the European BestPractice Guidelines. During annual conferences for nephrologists,the guidelines and data of our HD registry were presented. Results. There was an increase in the number of HD stations(from 25 p.m.p. to 75 p.m.p., P<0.001), in HD patients (from60 p.m.p. to 237 p.m.p., P<0.001) and in the incidence ofnew HD patients (from 54.3 p.m.p. to 103 p.m.p., P<0.01).The mean age of HD patients increased from 47.2±16.1years in 1996 to 56.0±14.9 in 2002 (P<0.001). Themain underlying cause of ESRD was chronic glomerulonephritis,but its rate decreased from 54.5% in 1996 to 27.5% in 2002 (P<0.001).The percentage of diabetics increased from 7.1% to 16.4%, P<0.05,and in hypertensive nephropathy from 3.1% to 10.9%, P<0.05.We observed improvement of the quality of HD in Lithuania duringthese 5 years. The percentage of patients on bicarbonate HDincreased from 7.1% in 1996 to 100% in 2002 (P<0.001). Thepercentage of patients receiving more than 12 h HD/week increasedfrom 30.8% in 1996 to 53.5% in 2002 (P<0.001). The mean Kt/Vin 1999 was 0.81±0.53, but it increased in 2002 to 1.22±0.27,P<0.001. In 2002, 84.6% of all HD patients were examinedfor HB_sAg, 82.3% for anti–HCV, 31.2% for anti-HB_s and57.1% for anti-HB_c. The percentage of patients receiving phosphatebinders increased from 65.2% in 1996 to 84.4% in 1997 and 90.5%in 2002. Serum parathyroid hormone (PTH) levels were measuredin 27.3% of HD patients in 1999 but in 85.2% of patients in2002. The mean haemoglobin (Hb) concentration increased from92±15.4 g/l to 105±14.7 g/l; the percentage ofpatients with Hb>100 g/l increased from 27.5% to 64% in 2001.The percentage of HD patients receiving epoetin was 94.6% in2001 as compared with 78% in 1997. There was a marked increasein the use of intravenous iron (from 7.5% patients in 1997 to70.8% in 2000). The mean weekly dose of Epo was lower in HDpatients receiving intravenous iron than in patients receivingoral iron. Conclusions. Over the period of 1996–2002 the HD servicessignificantly expanded in Lithuania. The introduction of EuropeanBest Practice Guidelines and the establishment of a HD registrywith feedback of the results stimulated the significant progressin the quality of HD and in the management of the patients.     

Relationship between serum albumin level before initiating haemodialysis and angiographic severity of coronary atherosclerosis in end-stage renal disease patients.

BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded.     

Impact of Helicobacter pylori infection on serum gastrin in haemodialysis patients.

BACKGROUND: Helicobacter pylori infection is associated with increased gastrin release in patients with normal renal function. Hypergastrinaemia is a common finding in haemodialysis patients and, in many cases, may be linked to H. pylori infection. The aim of this study was to examine the effect of H. pylori infection, and its eradication, on elevated gastrin levels in haemodialysis patients. METHODS: Eighty-nine dyspeptic patients were included in the study. While 44 patients had normal renal function, the remaining 45 were end-stage renal failure patients. Patients were assigned to one of four groups according to their H. pylori and renal function status. Infected patients were re-evaluated after 2 months following eradication treatment. Serum gastrin levels were measured in these groups both before and after eradication treatment. RESULTS: Haemodialysis patients with H. pylori infection had higher serum gastrin levels than did H. pylori negative haemodialysis patients (321+/-131 pg/ml vs 154+/-25 pg/ml) (P<0.05). Mean serum gastrin concentration was 152+/-21 pg/ml in the non-uraemic H. pylori-positive group. This value was 58+/-17 pg/ml in the non-uraemic H. pylori-negative group (P<0.05). There were significant decreases in serum gastrin levels from pre- to post-eradication of H. pylori in the infected haemodialysis and non-uraemic patient groups (312+/-131 pg/ml to 179+/-85 pg/ml and 152+/-21 pg/ml to 72+/-2.4 pg/ml respectively, P<0.05). Four patients in group Ib and 5 patients in group IIb who had persistent infection did not have a decrease in serum gastrin level. All patients with successful eradication had a decrease in serum gastrin concentration. CONCLUSION: Our findings suggest that H. pylori infection contributes to hypergastrinaemia in haemodialysis patients. More research is needed regarding the clinical consequences of hypergastrinaemia in these individuals.     

Relationships between plasma ferritin and aminotransferase profile in haemodialysis patients with hepatitis C virus

BACKGROUND.: HCV infection is a major complication among patients undergoingdialysis therapy throughout the world. In the years prior tothe use of human recombinant erythropoietin (rHuEpo), patientsundergoing haemodialysis were subjected to an excessive ironload as a consequence of frequent blood transfusions. Recentdata in the non-dialysis population have shown a positive correlationbetween iron deposits and the severity of HCV hepatitis andbetween iron deposition and an impaired response to interferontherapy. METHODS.: One hundred and five haemodialysis patients were studied. Everypatient was screened for HCV infection by ELISA II and HCV RNA.Serum biochemistries were analysed by SMAC20. Ferritin was measuredby radioimmunoassay. RESULTS.: The aminotransferase levels for the HCV positive (n=39) andnegative patients (n=66) were below the normal levels for thegeneral population. The mean values of aminotransferases andplasma ferritin were, however, higher in the HCV-positive patientsthan in the HCV-negative patients. A positive correlation betweenaminotransferases and plasma ferritin was evident in HCV-positivepatients, which was absent in the HCV-negative individuals.The histological severity of liver disease (n=7) was, however,not statistically related with the levels of either ferritinor aminotransferases. CONCLUSIONS.: HCV infection is a relevant variable when estimating iron depositsby measuring plasma ferritin. Accordingly, a misinterpretationof the actual amount of iron deposits may occur in HCV-positivepatients, which should be taken into account at the time ofplanning their iron reposition therapy. On the other hand, thelevel of iron deposits might have a significant role in theevolution of HCV-related liver disease.     

Decreased high-density lipoprotein cholesterol is associated with inflammation and insulin resistance in non-diabetic haemodialysis patients

Aim: Lower serum high‐density lipoprotein cholesterol (HDL‐C) is associated with inflammation, insulin resistance and poor cardiovascular outcomes in the general population. However, in a large‐scale study, the association between HDL and survival in haemodialysis patients was not present. The exact cause of lack of HDL‐C protection in the dialysis population is still obscure. Methods: A total of 89 stable non‐diabetic haemodialysis patients were recruited. Fasting serum biochemical parameters, complete blood counts and inflammatory markers were obtained before the mid‐week dialysis. Insulin resistance was assessed by the Homeostasis Model Assessment of Insulin Resistance (HOMA‐IR). Results: The mean age was 58.2 ± 13.1 years, 37 (41.6%) patients were male. The mean HDL‐C level was 56.3 ± 17.1 mg/dL. By bivariate correlation analysis, a lower serum HDL‐C level was related to higher body mass index (r = ?0.425; P < 0.001), higher triglyceride (r = ?0.479; P < 0.001) and higher HOMA‐IR (r = ?0.211; P < 0.05) levels. The serum HDL‐C level was also inversely related to high‐sensitivity C‐reactive protein (hsCRP) (r = ?0.297; P = 0.005) and tumour necrosis factor‐α (TNF‐α) (r = ?0.295; P = 0.005) and directly correlated with adiponectin (r = 0.560; P < 0.001). In multivariate linear regression analysis, HDL‐C was found to be directly correlated with adiponectin (β‐coefficient = 0.569; P < 0.001) and inversely correlated with TNF‐α (β‐coefficient = ?0.292; P = 0.001). Conclusion: A strong association between HDL‐C, inflammatory surrogates, and insulin resistance in this non‐diabetic, non‐obese haemodialysis patient group is demonstrated. The HDL‐C level is still a good parameter to screen high‐risk patients.     

5-methyltetrahydrofolate restores endothelial function in uraemic patients on convective haemodialysis.

BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for the development of atherosclerosis. In patients with chronic renal failure, the administration of folic acid or its metabolites reduces but does not normalize plasma homocysteine concentrations. Furthermore, homocysteine induces endothelial dysfunction by an increased inactivation of nitric oxide. METHODS: We examined the effect of the active metabolite of folic acid, 5-methyltetrahydrofolate (5-MTHF), 45 mg/week i.v. for 10 weeks, combined during the last 2 weeks with vitamin B12, 500 microg s.c. twice weekly, on homocysteinaemia and endothelial function in 15 patients undergoing convective haemodialysis. Endothelial function was evaluated by B-mode ultrasonography on the brachial artery. Flow-mediated dilation (FMD) was recorded during reactive hyperaemia produced by inflation of a pneumatic tourniquet. Nitroglycerine-mediated dilation (NMD) was recorded after administration of isosorbide dinitrate. Finally, the presence of the thermolabile variant of methyltetrahydrofolate reductase (t-MTHFR) was assessed by genotype analysis. RESULTS: Plasma homocysteine concentrations fell by 47% after treatment with 5-MTHF alone and by a further 13.6% after the addition of vitamin B12. The reduction was more marked in homo- and heterozygous patients than in normal genotypes for t-MTHFR. Flow-mediated endothelial vasodilation, measured by ultrasonography of the brachial artery, improved after administration of 5-MTHF (12.52+/- 2.47% vs. 7.03+/-1.65%; P<0.05), but there were no further changes following the addition of vitamin B12. CONCLUSIONS: Our study demonstrated that 5-MTHF administration not only reduced plasma homocysteine but also improved endothelial function in uraemic patients undergoing convective haemodialysis.     

Influence of body composition on 5 year mortality in patients on regular haemodialysis.

BACKGROUND: Reduction of body mass index (BMI) significantly affects mortality in haemodialysis (HD) patients, but it remains to be determined which of the body components influences mortality. METHODS: We examined the whole body composition of 262 HD patients by dual-energy X-ray absorptiometry (DEXA) (age: 60+/-12 years; HD duration 9+/-7 years; male/female: 177/85; diabetics, n=50) and subsequently followed mortality for 5 years. RESULTS: Patient age was significantly correlated with limb/trunk lean mass (LTLM) ratio (r=-0.350, P<0.01) and % fat content in whole tissue (r=0.145, P=0.02). There was a significant positive relationship between LTLM ratio and serum creatinine both in males (r=0.404, P<0.01) and females (r=0.267, P=0.01). Diabetic males and females both had a significantly lower LTLM ratio than non-diabetic males (P<0.01) and females (P<0.04). During the 5 years, 65 patients (24.8%) died mainly of cardiovascular diseases and infections. BMI was lower in the expired group than in survivors (P<0.04). LTLM ratio was significantly reduced in the expired group compared with the surviving males (0.629+/-0.097 vs 0.707+/-0.094; P<0.01) and females (0.611+/-0.101 vs 0.651+/-0.078; P<0.01). Cox's proportional hazards analysis revealed that the reduction of LTLM ratio was a significant determinant of death in men (P<0.01), while a lower percentage of fat content of trunk was a significant determinant of death in women (P<0.01). In contrast, BMI did not influence mortality in either sex. CONCLUSIONS: Measurements of regional lean and fat mass volumes by DEXA may be useful for predicting death in patients receiving long-term HD.