Systemic lupus erythematosus: A follow-up study of Japanese patients with end-stage renal failure treated with haemodialysis

Summary: In order to explore the clinical course of Japanese patients with systemic lupus erythematosus (SLE) in end-stage renal failure, the clinical findings from 26 patients who had received haemodialysis were analysed. Each patient was followed for 72 months from the onset of clinical lupus nephritis to the initiation of haemodialysis. In most patients, renal disease progressed to end-stage renal failure despite clinical quiescence of SLE, which remained inactive throughout haemodialysis treatment. Seven patients (27%) had clinically active SLE with high dose prednisolone (mean; 49.3 mg per day) at initiation of haemodialysis. These patients had relatively rapid progression of their renal failure and 2 patients died within 1 month of their first haemodialysis. During the follow-up period from starting haemodialysis for an average of 44 months, most patients received ongoing haemodialysis while their SLE remained clinically inactive. Six patients (23%) died, 5 of those within 1 month from starting hemodialysis. the results of this long-term follow up of a large number of haemodialysis patients with lupus nephritis indicate that: (i) most patients with lupus nephritis undergoing haemodialysis have an excellent survival rate; and (ii) patients with active SLE at initiation of haemodialysis have a high mortality rate (within 1 month). We therefore conclude that more effective treatment for SLE in the presence of renal failure is required for these patients.     

Evaluation of coagulation and fibrinolysis in haemodialysis patients at different haematocrit levels: Comparison between patients with and without diabetes

SUMMARY: There is an insufficient number of reports concerning the optimal haematocrit level for haemodialysis patients with diabetes. Although many reports have indicated that recombinant human erythropoietin (rHuEPO) therapy does not influence the incidence of intravascular thrombosis, no study has focused its attention on the difference of the coagulation-fibrinolysis system between haemodialysis patients with and without diabetes. We studied eight patients with diabetes and seven patients without diabetes who had been undergoing regular haemodialysis. In all 15 patients, rHuEPO administration was started at a haematocrit level of 20% and toe haematocrit tevels were gradually increased from 20 to 30%. Coagulation and fibrinolysis functions, measured at haematocrit levels of 20,25 and 30%, respectively, were compared between the two groups. In the diabetic group, platelet count, fibrinogen, thrombin-antithrombin III complex, frtmn/fibrinogen degradation products = D dimer, platelet factor 4 and platelet adhesion were statistically higher ( P < 0.05), and plasminogen and α2-plasmin inhibitor was statistically lower ( P < 0.05) than those in the non-diabetic group, even at the 20% level. These abnormalities at the baseline were extremely enhanced in connection with haematocrit increased by rHuEPO. the diabetic group, in particular, showed greater increases of platelet factor 4, platelet adhesion and thrombomodulin and a decrease of α2-plasmin inhibitor from the 20% to the 30% level ( P < 0.05) than the non-diabetic group. These findings suggest that haemodialysis patients with diabetes generally have enhanced thrombotic parameters compared with haemodialysis patients without diabetes, and the increase of haematocrit makes the difference greater. Accordingly, the target level of haematocrit for patients with diabetes should be set separately from that of patients without diabetes.     

Correlation between parathyroid hormone, bone alkaline phosphatase and N-telopeptide of type 1 collagen in diabetic and non-diabetic haemodialysis patients

BACKGROUND: Haemodialysis (HD) patients with diabetes mellitus often have renal osteodystrophy (ROD) characterized by reduced bone turnover, but little is known about the correlation between bone formation and bone resorption in this population. METHODS: The authors measured serum parathyroid hormone (PTH), bone alkaline phosphatase (BAP), N-telopeptides of type 1 collagen (NTx) and fasting glucose in 48 patients with diabetic nephropathy (DN) and 80 patients with glomerulonephritis (non-DN) who had received or=5 years HD (r = 0.568) this correlation was similar to that in the non-DN group (r = 0.653), whereas there was no significant correlation in those receiving <5 years HD. Patients receiving >or=5 years HD had a comparable glucose level (111.1 +/- 19.2 mg/dL) to the non-DN group, whereas those receiving <5 years had a higher level (196.1 +/- 53.1 mg/dL). CONCLUSION: Differences in the interaction between bone cells between DN and non-DN patients are one potential cause of lower bone turnover in the former group. Research of this correlation is needed to increase understanding of the complexities of bone metabolism in DN patients.     

Influence of ANF on the cardiovascular response to volume expansion in haemodialysis patients

Plasma ANF concentration in uraemic patients is very sensitiveto changes in extracellular volume. It is unknown, however,if the release of this vasoactive hormone has a compensatoryrole in the haemodynamic response to extracellular volume expansionin these patients. We investigated the effect of isolated ultrafiltrationfollowed by isovolumic re-expansion by saline in seven haemodialysispatients. The experiment was repeated on two occasions and theUF rate as well as the rate of volume re-expansion in the twostudies were accurately matched. During the phase of volumere-expansion, we infused either ANF (0.83 µg/mm) or aplacebo, in random order and cross-over. Central venous pressure,arterial pressure, haematocrit, and plasma ANF concentrationwere measured in baseline conditions, after ultrafiltration,and 0, 15, and 30 mm after isovolumic re-expansion. In the control experiment (placebo), isolated ultrafiltrationcaused a marked reduction in central venous pressure and inarterial pressure and a pronounced haematocrit increase. Thesechanges were reversed by volume re-expansion. In the activeexperiment, during the phase of volume re-expansion ANF infusiondoubled plasma ANF concentration as compared to control experimentbut it did not affect the ongoing haemodynamic response northe haematocrit changes. Doubling of plasma ANF concentration has no influence on thehaemodynamic and microcirculatory adaptations to acute volumeexpansion in haemodialysis patients. The data indicate thatit is unlikely that raised plasma ANF concentration has a majorrole in the cardiovascular response to acute extracellular volumeexpansion in these patients.     

Vitamin A and zinc status in patients on maintenance haemodialysis

BACKGROUND: The objective of this study was to assess the vitamin A and zinc serum levels in patients undergoing haemodialysis (HD) in the city of Recife, in the north-eastern region of Brazil. METHODS: The study comprised 55 patients and 28 healthy controls. The retinol and zinc serum concentrations were analysed by using high-performance liquid chromatography (HPLC) and atomic absorption spectrophotometry, respectively. RESULTS: The mean retinol serum concentration in patients (2.50 +/- 0.86 micromol/L) was significantly greater (P < 0.001) than that found in controls (1.26 +/- 0.86 micromol/L). The retinol serum levels in the patients were as follows: 47.3% of the patients had elevated levels (>/= 2.24 and < 3.50 micromol/L); 16.4% of the patients had serum levels >/= 3.50 micromol/L, which indicated hypervitaminosis; and 9.1% of the patients had serum levels below the normal range (<1.05 micromol/L), a rate that among the controls was 42.9% (P < 0.01). In regard to zinc, the serum levels found in the patients (10.59 +/- 3.12 micromol/L) were similar to those found in the controls (11.43 +/- 2.82 micromol/L) (P > 0.05). Although 49.1% of the patients and 35.7% of the controls were classified as deficient in zinc, this difference was not statistically significant (P > 0.05). RESULTS: The results identified a high prevalence of zinc deficiency in the groups studied, and point to a trend towards more elevated retinol serum levels in patients undergoing dialysis as compared with those in healthy controls.     

Accumulation of cyanide and thiocyanate in haemodialysis patients.

BACKGROUND: Cyanide is a toxic agent, and its detoxification product, thiocyanate, may be a major pathogenetic substance in uraemia. Recent studies examining the myeloperoxidase(MPO)/thiocyanate system have suggested a link between thiocyanate and atherosclerosis. However, inaccuracies in conventional assays for cyanide and thiocyanate have limited the understanding of their metabolism in haemodialysis (HD) patients. METHODS: We used high-performance liquid chromatography to measure cyanide in erythrocytes and thiocyanate in plasma in 43 HD patients and in a group of 46 healthy controls that included 15 current smokers. To clarify the metabolic conversion of cyanide to thiocyanate in uraemic patients, we also measured cysteine and sulfate. We then used stepwise regression analysis to analyse factors that determine erythrocyte cyanide and plasma thiocyanate. RESULTS: Mean cyanide and thiocyanate were significantly greater in HD patients than in non-smoking controls. However, cyanide was far below lethal concentrations in dialysis patients. Thiocyanate was six to seven times greater in HD patients than in non-smoking controls, and decreases in thiocyanate following dialysis were only 19.3+/-3.5%. Multiple regression analysis showed a positive correlation between cyanide and thiocyanate in controls, but a negative correlation in HD patients. In patients, an inverse relationship between thiocyanate and BUN was also observed. CONCLUSIONS: The elevation of thiocyanate in patients undergoing dialysis probably is secondary to both limited efficiency of HD and deranged metabolism of cyanide and thiocyanate. Because thiocyanate is a preferred substrate for MPO, it may play a role in uraemic complications including cardiovascular events.     

IL-1beta, TNF-alpha and IL-6 release from monocytes in haemodialysis patients in relation to dialytic age.

BACKGROUND: It has been suggested that changes in immune response to infectious agents in patients on haemodialysis might be due to impaired monocyte function; uraemic and haemodialysed patients overproduce proinflammatory cytokines, such as interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). METHODS: We quantitated the cytokines released into the plasma and into the supernatants of 24-h cultured purified monocytes, under basal conditions and after stimulation by lipopolysaccharide from Escherichia coli, in 15 healthy subjects (CON), 20 uraemic patients who had not yet started dialysis (CRF) and 60 haemodialysed patients (HD), who were divided into three groups of 20 patients corresponding to short-, medium- and long-term dialysis. RESULTS: Monocytes from HD patients spontaneously secreted significantly higher levels of cytokines than those from controls and uraemic patients who had not yet started dialysis. After stimulation with lipopolysaccharide (LPS), cytokine levels in culture supernatants of cells from HD patients were significantly lower than those from controls and uraemic patients. Moreover, levels of cytokines in monocyte supernatants and plasma from short-, medium- and long-term haemodialysed patients decreased progressively with dialytic age. Monocytes from haemodialysed patients tended to be constitutively active, but their ability to secrete proinflammatory cytokines was inversely correlated with dialytic age. CONCLUSIONS: These results indicate that prolonged treatment with dialysis can be considered a form of chronic stress that causes the progressive activation of monocytes, which ultimately leads to monocyte exhaustion and dysfunction.     

Determination of oxidative stress and cellular inflammation in patients with diabetic nephropathy and non-diabetic nephropathy being administered hemodialysis treatment due to chronic renal failure

Objectives: We aimed to evaluate oxidative stress [8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA)] endothelial damage [asymmetric dimethylarginine (ADMA)] and markers of cellular inflammation [interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), neopterin (NP) and high-sensitivity C-reactive protein (hsCRP)] in patients with diabetic nephropathy (DN) and non-diabetic nephropathy who were being administered hemodialysis treatment because of chronic renal failure. Methods: In determining 8-OHdG, IL-6 and TNF-α levels, Enzyme-Linked Immuno-Sorbent Assay method was used. Serum MDA, ADMA and NP levels were determined by using high performance liquid chromatography (HPLC). And hs-CRP values were measured with nephelometric method. Results: Serum 8-OHdG and MDA levels were found statistically to have increased when compared with those of the control group in patients groups after dialysis. However, serum ADMA and neopterin levels were observed statistically to have decreased when compared with those of the control group in patients groups after dialysis. But, decreases on ADMA and neopterin levels are still much higher than those of control. IL-6 and TNF-α levels were found to have increased when compared with those of control group in patients groups before dialysis. Conclusion: The oxidative stress in patients with DN, who were being treated with hemodialysis due to chronic renal failure, was higher than that of non-DN patients who were being treated with hemodialysis. In contrast with this, inflammation occurring in non-DN patients was found to have been higher than that of in patients with DN.     

Diabetic retinopathy may predict the renal outcomes of patients with diabetic nephropathy

Background: The patients with Type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) are prone to develop diabetic nephropathy (DN). In this study, we aimed to clarify the relationship between DR and the progression of DN in patients with T2DM.

Methods: In the cross-section study, 250 patients with T2DM and biopsy-proven DN were divided into two groups: 130 in the DN without DR group (DN group) and 120 in the DN?+?DR group. Logistic regression analysis was performed to identify risk factors for DR. Of the above 250 patients, 141 were recruited in the cohort study who received follow-up for at least 1 year and the influence of DR on renal outcome was assessed using Cox regression. Renal outcome was defined as the progression to end-stage renal disease (ESRD).

Results: In the cross-section study, the severity of glomerular lesions (class IIb?+?III) and DM history?>10 years were significantly associated with the odds of DR when adjusting for baseline proteinuria, hematuria, e-GFR, and interstitial inflammation. In the cohort study, a multivariate COX analysis demonstrated that the DR remained an independent risk factor for progression to ESRD when adjusting for important clinical variables and pathological findings (p?Conclusions: These findings indicated that the severity of glomerular lesions was significantly associated with DR and DR was an independent risk factor for the renal outcomes in patients with DN, which suggested that DR may predict the renal prognosis of patients with T2DM and DN.     

Pentraxin 3 is elevated in haemodialysis patients and is associated with cardiovascular disease.

BACKGROUND: Pentraxins are mediators of inflammation as well as markers of the acute-phase reaction. While elevation of C-reactive protein (CRP) in patients with renal failure and its association with cardiovascular disease is well described, there are no data on pentraxin 3 (PTX3) in this population. METHODS: Plasma was obtained from 44 chronic haemodialysis (HD) patients, 35 peritoneal dialysis (PD) patients, 39 patients with chronic renal failure (CRF) not on dialysis therapy and 14 age-matched normal subjects. PTX3 production in whole blood was also investigated in samples taken before and during HD. RESULTS: PTX3 plasma levels were significantly higher in HD patients (5.8 +/- 0.6 ng/ml) compared with the other three groups. There were no significant differences between PD patients (1.5 +/- 0.4 ng/ml), CRF patients (1.5 +/- 0.4 ng/ml) and normal subjects (0.76 +/- 0.2 ng/ml). In dialysis patients, PTX3 levels correlated significantly with time on renal replacement therapy (RRT) and with weekly erythropoietin dose. PTX3 levels were significantly higher in patients with coronary artery disease and peripheral artery disease compared with those without. During a single HD session, PTX3 production was higher in whole blood samples taken after 3 h HD compared with samples taken before HD. CONCLUSIONS: PTX3 levels are markedly elevated in HD patients. The increase in PTX3 production in whole blood after HD indicates that the HD procedure itself contributes to elevated PTX3 levels in HD patients. The association between PTX3 and cardiovascular morbidity suggests a possible connection of PTX3 with atherosclerosis and cardiovascular disease in HD patients.     

Increased frequency of the apolipoprotein E2 allele in maintenance haemodialysis patients in Taiwan

SUMMARY: Apolipoprotein E (apo E) regulates the metabolism of lipoproteins. Three different apo E alleles (ε2, ε3 and ε4) produce the apo E isoproteins, apo E2, apo E3 and apo E4. Previous studies had revealed that lipid abnormalities might contribute to the development and progression of kidney diseases. Thus, the apo E gene polymorphism may be associated with end-stage renal disease. to investigate the distribution of apo E genotype in patients under haemodialysis in Taiwan, we examined 205 dialysis patients and 103 age-matched normal controls. the apo E gene polymorphism was analysed by the use of polymerase chain reaction. Our study revealed that the frequency of apo E2 allele was significantly higher in dialysis patients (8.0%) than in normal controls (1.9%; P <0.01). the E3 and E4 allele frequencies were not significantly different between the groups. Our findings indicate that apo E polymorphism was apparently associated with the development of end-stage renal disease in Taiwan.     

Quality of sleep and health-related quality of life in haemodialysis patients.

BACKGROUND: Sleep complaints are common in haemodialysis patients. In the general population, insomnia impacts negatively on health-related quality of life (HRQoL). The objective of this study was to examine the association between quality of sleep and HRQoL in haemodialysis patients independent of known predictors of HRQoL. METHODS: Quality of sleep was measured using the Pittsburgh Sleep Quality Index (PSQI) and HRQoL was measured using the Medical Outcomes Study 36-item Short Form (SF-36) in 89 haemodialysis patients. RESULTS: Sixty-three (71%) subjects were 'poor sleepers' (global PSQI >5). The SF-36 mental component summary (MCS) and physical component summary (PCS) correlated inversely with the global PSQI score (MCS, r = -0.28, P < 0.01; PCS, r = -0.45, P < 0.01). The PCS score also correlated with age (r = -0.24, P = 0.02), haemoglobin (r = 0.21, P = 0.048) and comorbidity (r = -0.40, P < 0.01), and mean PCS was lower in depressed subjects (26.2 vs 35.9, P = 0.02). Subjects with global PSQI >5 had a higher prevalence of depression, lower haemoglobin and lower HRQoL in all SF-36 domains. The global PSQI score was a significant independent predictor of the MCS and PCS after controlling for age, sex, haemoglobin, serum albumin, comorbidity and depression in multivariate analysis. CONCLUSIONS: Poor sleep is common in dialysis patients and is associated with lower HRQoL. We hypothesize that end-stage renal disease directly influences quality of sleep, which in turn impacts on HRQoL.     

Histomorphometric analysis of aplastic bone disease in chronic renal failure at initiation of haemodialysis: Relation to aluminum and parathormone

SUMMARY: We studied bone histology of 134 uraemic patients without a history of vitamin D administration at the start of haemodialysis. Patients were categorized according to bone histology as follows: aplastic bone disease (ABD), ostitis fibrosa, mixed type, mild hyperparathyroidism and osteomalacia. On initiation of haemodialysis, ABD was observed in 48.5% of patients. the average age of the ABD group (50.8 ± 12.5 years) was significantly higher than that of patients with other histologies ( P <0.01). Serum parathyroid hormone (PTH) and alkaline phosphatase (ALP) concentrations were lower ( P <0.01) in the ABD group, especially in patients with diabetes mellitus. Patients with diabetes mellitus and ABD had lower serum concentrations of PTH and ALP than non-diabetic patients, suggesting that depressed PTH may be related to ABD. Eleven (55%) of the 20 patients who were receiving A1(OH)₃ also had ABD. A direct relationship was observed between serum aluminum concentration and aluminum-positive bone surface ( r =0.60; P <0.01). Aluminum staining was more frequently observed in the ABD group than in the non-ABD group ( P <0.01). Because serum intact-PTH concentrations correlate with osteoid surface area, fibrosis volume and bone formation rate, it may be a useful marker of bone histology in renal osteodystrophy. These results suggest that, in addition to conservative treatment with A1(OH)₃, other factors may be involved in the formation of ABD which is often present at the start of haemodialysis.     

Identification of risk factors on secondary hyperparathyroidism undergoing long-term haemodialysis with vitamin D3

In order to evaluate the clinical outcome as well as the effectof vitamin D3 treatment on secondary hyperparathyroidism (SHPT)in the patients undergoing long-term dialysis therapy, we conducteda long-term follow-up survey on the demographic characteristicsof 425 patients who were observed for more than 3 years. Allpatients were treated with daily 1(OH)D3 treatment after theinitiation of dialysis. Among them the percentage of patientsneeding parathyroidectomy was 4.9% aggravation of SHPT, 11.8%an increase of the parathyroid hormone (PTH) level without radiographicalabnormalities, 17.4% stable, 56.2% and a decrease of the PTHlevel, 9.7% at the final observation. The average PTH levelsincreased year by year irrespective of the difference of originalrenal disease. Gender, age at the start of dialysis, originalrenal disease, duration of dialysis treatment, the decade ofstarting dialysis, the degree of phosphate control, and thePTH level at starting dialysis were analysed as potential riskfactors for SHPT, and assessed by multivariate analysis. Multivariateanalysis revealed that only the terms of duration of dialysisand the PTH level at starting dialysis were the significantrisks for developing overt SHPT. Logistic regression analysisrevealed that the relative risk was significantly higher inthe patients with more than 10 years history of dialysis andin those with the carboxyterminal PTH levels at the start ofdialysis being more than 5 ng/ml. These results suggest thatthe treatment with daily low-dose vitamin D3 administrationafter dialysis initiation is imperfect; therefore some prophylactictherapy from the predialysis stage is necessary to prevent overtSHPT, which will occur after long-term haemodialysis.     

Hepatitis C, HCV genotypes and hepatic siderosis in patients with chronic renal failure on haemodialysis in Brazil.

BACKGROUND: The aim of this study was to investigate the HCV genotypes, hepatic siderosis, inflammatory activity and fibrosis of the liver in patients with chronic renal failure (CRF) on haemodialysis in Brazil. METHODS: A cohort of 72 CRF patients was compared with a group of 65 candidates for blood donation (CBD). For the subjects selected, who tested positive for anti-HCV antibodies and were HCV-PCR positive, a protocol with epidemiological, clinical and laboratory information was completed. An ultrasound-guided liver biopsy was performed and histological analysis of liver fragments was carried out. The presence of HCV-RNA in plasma was established by nested-RT-PCR. The genotype was determined by Restriction Fragment Length Polymorphism (RFLP) analysis of the PCR product. RESULTS: HCV genotype 1 was predominant in both groups, but genotype 2 was the second most common amongst CRF patients, and there was a significant difference when compared with the CBD group (P=0.016). Regarding inflammation and fibrosis, no significant difference was observed in the histology of the liver between the study groups. Siderosis of the liver was more prevalent in the CRF group (P=0.000). Severe complications of liver biopsies were reported in 10 CRF patients (13.2%). CONCLUSIONS: Genotype 2 was observed more frequently in the haemodialysis group. No statistically significant difference was detected between the CRF and CBD groups with regard to both inflammatory response and liver fibrosis. Hepatic siderosis has been attributed to excessive iron administration. As percutaneous liver biopsy resulted in severe complications, we suggest that other procedures of evaluating liver damage in CRF patients should be looked at thoughtfully.     

Growth hormone response to acute growth hormone releasing hormone administration in uraemic patients on haemodialysis.

To examine the response of growth hormone (GH) to growth hormone releasing factor (GHRF) in patients on haemodialysis, we performed the acute GHRF test (50 micrograms administered intravenously as a bolus) in 10 uraemic male patients on haemodialysis and eight normal controls. Each patient was tested before and after a haemodialysis session (at 08.30 and 12.30). Controls were tested on the same time schedule. At 08.30, patients had significantly greater basal and peak GH values (2.5 +/- 0.6 and 27.8 +/- 5.5 micrograms/l) than controls (0.68 +/- and 11.5 +/- 4 micrograms/l). After the haemodialysis session, basal and peak values declined significantly (P less than 0.01) in the uraemic group (0.5 +/- 0.03 and 3.1 +/- 1.1 micrograms/l), whereas the controls did not show such a change in the 12.30 test. Basal and intratest glycaemic values were comparable both before and after haemodialysis. After dialysis test results did not change either with the use of glucose-free dialysate or with bicarbonate buffer. Uraemic patients display a greater GH response to GHRF injection than normal subjects, and this response decreases after haemodialysis. The degree of reduction has no relationship with either glycaemia or the dialysate buffer. We suggest that other GH secretion regulating factors are altered by the haemodialysis procedure.     

Influence of haemodialysis and left ventricular failure on peripheral A(2A) adenosine receptor expression.

BACKGROUND: Haemodialysis (HD) sometimes accelerates left ventricular failure (LVF). As adenosine (ADO) is strongly implicated in cardiovascular functions, particularly via A(2A) receptor activation and as changes of peripheral A(2A) receptors mirror changes occurring in the cardiovascular system, we examined the influence of HD and LVF on both ADO plasma concentration and the expression of A(2A) receptors (i.e. Bmax, K(D) and mRNA amount) of peripheral blood mononuclear cells. METHODS: This cross-sectional study included 61 chronic renal failure (CRF) patients: 41 without LVF (24 haemodialysed and 17 undialysed) and 20 with LVF (9 haemodialysed and 11 undialysed). Ten LVF patients without CRF and 10 healthy subjects were also examined. RESULTS: (i) Bmax values of CRF patients without LVF were significantly decreased in undialysed patients compared with haemodialysed patients, and compared with controls (69 +/- 25 vs 98 +/- 33 vs 180 +/- 60 fmol/mg of protein, P < 0.05). Bmax values of CRF patients with LVF were lower in undialysed patients than in haemodialysed patients (60 +/- 27 vs 101 +/- 27 fmol/mg of protein, P < 0.05). Bmax values of LVF patients without CRF were lower than in controls (51 +/- 19 vs 180 +/- 60 fmol/mg of protein). (ii) A(2A) mRNA expression was increased in haemodialysed patients compared with controls (20.2 +/- 0.75 vs 17.6 +/- 1.3, P < 0.05). (iii) ADO plasma levels were high in haemodialysed patients and further increased during the HD sessions. CONCLUSION: The number of A(2A) receptors was decreased by CRF with or without LVF. However, this decrease was less important in haemodialysed patients. The changes in peripheral A(2A) receptor expression suggest a significant inflammatory response to HD and heart or kidney failure. Whether these changes do reflect alterations in cardiomyocytes needs further investigation.     

Association of interferon-gamma +874A polymorphism with reduced long-term inflammatory response in haemodialysis patients.

BACKGROUND: We have studied the effects of interferon (IFN)-gamma allelic variations on expression levels of pro- and anti-inflammatory cytokines and on long-term inflammatory status in haemodialysis patients. METHODS: Genotyping was performed in 123 patients for single nucleotide polymorphisms in the first intron of the IFN-gamma gene (+874 T/A). They were prospectively followed for 2 years. Cytokine mRNA levels in whole blood cells (detected by real time (RT)-PCR technique) and serum C-reactive protein (CRP) concentrations were compared in patient groups with different IFN-gamma genotypes. Serum CRP was evaluated every month and inflammatory state was defined as percent of abnormal values (above 5 mg/l) over total determinations. Of the total, 102 patients survived and completed 24+/-1 monthly CRP determinations. The IFN-gamma +/-874 A/A, 'low-producer' genotype was associated with decreased (P<0.05) mRNA levels of IFN-gamma and of interleukin-6 and with a lower (P<0.05) frequency of CRP elevation (37+/-6%) than the +/-874 A/T and T/T, 'intermediate and high-producer' genotypes (59+/-6%, and 60+/-5%, respectively). The mRNA levels of tumor necrosis factor-alpha, IL-10 and of transforming growth factor-beta1 were not different in the three groups of patients. Pooled analysis in deceased (10+/-3 monthly CRP determinations) and survived patients confirmed the results obtained in the patients who completed the follow-up period. CONCLUSIONS: The 'low-producer' IFN-gamma +874 A/A genotype was associated with a preventive effect on long-term CRP elevation in haemodialysis patients possibly mediated by decreased gene expression of IFN-gamma and IL-6.