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Background: Mediterranean-style diet has been considered for its important beneficial effects on the progression of CV disease. Wine is an important component of the Mediterranean diet, and moderate wine drinkers have lower mortality rates than nondrinkers and heavy drinkers in epidemiologic studies. The beneficial effects of red wine are thought to be dependent on the polyphenol compounds such as resveratrol that exhibit potent antioxidant activity. However, white wine, although lacking polyphenols, contains simple phenols, such as tyrosol (Tyr) and hydroxytyrosol (OH-Tyr), characteristic also of extra-virgin olive oil, which may share similar antioxidant and inflammatory properties. Patients and Methods: The effect of white wine and extra-virgin olive oil on inflammatory markers was evaluated in 10 healthy volunteers and in 10 patients with CKD (chronic kidney disease) K-DOQI stage III-IV in a prospective, single blind, randomized, cross-over trial. After two weeks of wash-out from alcoholic beverages, subjects were randomized to a cross-over design A-B or B-A of a 2-week treatment with white wine (4 ml/kg body weight, 0.48 g/kg of alcohol 12%, corresponding to 2-3 glasses/daily) and extra-virgin olive oil (treatment A) or extra-virgin olive oil alone (treatment B). The two study periods were separated by a two-week wash-out period. At baseline and at the end of each treatment, plasma levels of inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8) concentration were determined. Urinary levels of Tyr, OH-Tyr, and their metabolites were measured at the same time. Results: During combined consumption of white wine and extra-virgin olive oil (treatment A), plasma levels of CRP and IL-6 decreased from 4.1 ± 1.8 to 2.4 ± 1.9 mg/l (p < 0.05) and from 5.3 ± 3.2 to 3.4 ± 2.3 mg/l (p < 0.05) in CKD patients. CRP decreased from 2.6 ± 1.2 to 1.9 ± 0.9 mg/l (p < 0.05), and IL-6 decreased from 2.2 ± 1.8 to 1.7 ± 1.3 mg/l (p = ns) in healthy volunteers. No significant variation versus baseline was observed during treatment B. A significant increase in urinary Tyr and OH-Tyr was observed during treatment A (white wine and extra-virgin olive oil). Conclusions: Plasma markers of chronic inflammation were significantly reduced in CKD patients during the combined consumption of white wine and olive oil, suggesting a possible anti-inflammatory effect of this nutritional intervention.

Background Statins reduce lipid levels, inflammation and cardiovascular events in patients with coronary artery disease; CKD patients show increased risk of cardiovascular and increased plasma levels of IL-6 and IL-8. Aim To evaluate the in vitro effect of simvastatin (S) or fluvastatin (F) on the lipopolysaccharide (LPS) stimulated secretion of IL-6 and IL-8 from monocytes of chronic kidney disease patients (CKD) in K-DOQI stages 3-5. Methods and subjects Monocytes enriched peripheral blood (PBMC) from 28 CKD (15 in K-DOQI stages 3-4, Group I, and 13 in K-DOQI stage 5 on hemodialysis, Group II) and 10 healthy subjects (HS), were isolated by Ficoll-gradient centrifugation. Cells were incubated with LPS 100 ng/ml or with LPS plus increasing doses of statins (from 10−6 to 10−8 M ) for 24 h. Surnatant IL-6 and IL-8 concentrations were determined by EIA. Results Basally the mean concentration of IL-6 and IL-8 was higher in patients than in HS and in Group II than in Group I (IL6: HS 285 ± 77 pg/ml, Group I 365 ± 178 pg/ml, Group II 520 ± 139 pg/ml- IL8 HS 180 ± 75 pg/ml, Group I 1722 ± 582 pg/ml, Group II 4400 ± 1935 pg/ml). After addition of LPS the mean concentration of IL-6 and IL-8 increased in all groups (IL6: HS 1740 ± 178 pg/ml, Group I 3754 ± 672 pg/ml, Group II 4800 ± 967 pg/ml; IL8: HS 450±132 pg/ml, Group I 9700±2837 pg/ml, Group II 11608 ± 2316 pg/ml). After the addition of LPS plus increasing doses of S or F from 10−10 to 10−6 M, a significantly lower cytokine concentration compared to the data after LPS alone was observed (IL6: HS 45%, Group I 75%, Group II 50%; IL8: HS 100%, Group I 65%, Group II 35%). Conclusions These data confirm that cytokine release is increased in CKD patients and that is highest in the most severe patients. Furthermore they suggest that fluvastatin or simvastatin can be used in order to reduce the high cardiovascular risk.

Ezetimibe (E) is a new cholesterol adsorption inhibitor which prevents the adsorption of dietary and biliary cholesterol by binding to a recently described cholesterol transporter. This pilot study was performed to evaluate the safety and the low-density lipoprotein (LDL)-C and C-reactive protein lowering efficacy of atorvastatin (A) and of the association of A plus E in five renal transplant patients with hypercholesterolemia and mild renal functional impairment receiving cyclosporine-A (CsA). Patients received for three periods, each of 3 weeks, A at a dose of 20 mg/day; A at a dose of 10 mg/day and finally, A 10 mg plus E 10 mg daily. The medications were well-tolerated and no important clinical or laboratory (muscle enzyme, creatinine clearance and CsA concentration) abnormalities were observed throughout the study period. A alone lead to target LDL-C values only in two of five patients and did not significantly reduce the mean CRP values. The combination of E plus A produced the lowest lipid levels and significantly reduced CRP mean values and allowed all patients to attain target levels of LDL-C: total cholesterol decreased from 240 +/- 42 (mean +/- S.D.) to 171 +/- 34 mg/dl, LDL-C from 129 +/- 32 to 87 +/- 21 mg/dl, plasma triglycerides from 330 +/- 54 to 194 +/- 71 mg/dl and CRP from 6.2 +/- 1.9 to 3.9 +/- 2.4 mg/l (P < 0.05 for all). This pilot study suggests that the co-administration of E and A at 10 mg/day in renal transplant patients receiving CsA is well-tolerated and effective in reducing important cardiovascular risk factors.

Background: A pharmacoeconomic analysis of the RISCAVID database aimed at assessing the cost effectiveness of phosphate binders in preventing CV mortality and morbidity over 7 years was performed. Methods: Morbid or fatal events occurring in 750 chronic HD patients were recorded. Statistical analysis evaluated the distribution of variables and the effect of sevelamer on survival. A cost-effectiveness evaluation was performed using a probabilistic model based on a Markov chain. Results: Multivariate analysis showed that treatment with sevelamer was associated with a reduced stroke incidence by 52% (p = 0.04) and reduced levels of C-reactive protein (p < 0.01). Cost-effectiveness evaluation evidenced a 33% decrease in hospital-days for patients treated with sevelamer, with and without comorbidities compared to patients undergoing calcium binders treatment. Conclusion: Treatment with sevelamer was associated with a reduced risk of stroke in HD patients, with a clear saving on disease-related costs for the Italian National Healthcare System.

Resistance to erythropoiesis-stimulating agents (ESAs) is often associated with chronic inflammation. Here, we investigated how anaemia, ESA resistance and the plasma levels of biological markers of inflammation could influence all-cause and cardiovascular disease morbidity and mortality.Seven hundred and fifty-three haemodialysis (HD) patients (mean age 66 ± 14.2 years, mean dialytic age 70 ± 77 months and diabetes 18.8%) were enrolled and followed-up for 36 months. Demographic, clinical and laboratory data, co-morbidity conditions, administered drugs, all-cause mortality and fatal/non-fatal cardiovascular (CV) events were recorded. We measured ESA resistance index, C-reactive protein (CRP) and interleukin-6 (IL-6).Six hundred and fifty-one patients (86.4%) received ESAs. Patients with haemoglobin level11 g/dL (n = 225) showed increased risk of CV [relative risk (RR) 1.415, 95% confidence interval (CI) 1.046-1.914] and overall mortality (RR 1.897, 95% CI 1.423-2.530) versus patients with haemoglobin levels11 g/dL. ESA resistance values categorized into quartiles (Quartile I5.6, Quartile II 5.7-9.6, Quartile III 9.7-15.4 and Quartile IV15.4) correlated with all-cause mortality and fatal/non-fatal CV events (RR 1.97, 95% CI 1.392-2.786; RR 1.619, 95% CI 1.123-2.332, respectively). Furthermore, albumin was significantly reduced versus reference patients and correlated with all-cause mortality and CV events; CRP levels were higher in hyporesponders (Quartile IV) (P0.001) and predicted all-cause mortality and CV events. IL-6 but not CRP was a strong predictor of ESA resistance.ESA responsiveness can be considered a strong prognostic factor in HD patients and seems to be tightly related to protein-energy wasting and inflammation.

Cardiovascular disease is a significant complication in chronic kidney disease (CKD) and a major cause of death in dialysis patients. Clinical studies have shown that anemia is associated with reduced survival in patients undergoing chronic hemodialysis. Furthermore, an association between anemia and adverse cardiovascular outcomes has also been observed in patients with earlier stages of CKD not yet requiring dialysis. Although this fact still remains controversial, high-efficiency on-line hemodiafiltration (HDF) has been shown to improve anemia and to reduce the need for erythropoietin-stimulating agents in hemodialysis (HD) patients. This positive effect has been attributed to the fact that the convective methods might remove some protein-bound erythropoietic inhibitor substances. Moreover, in HD patients, renal anemia is linked to the inflammatory state of uremic syndrome. It is also worth nothing that the improvement in anemia is associated with a reduced inflammatory state in patients undergoing on-line HDF. Here, we have reviewed the current knowledge of the effect of dialysis technique on renal anemia.

Background: Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anemia. Vitamin E is a fat-soluble antioxidant that plays a central role in reducing lipid peroxidation and inhibiting the generation of reactive oxygen species. The aim of this cross-over randomized study was to compare the effects of a vitamin E-coated polysulfone (Vit E PS) membrane and a non-vitamin E-coated polysulfone (PS) membrane on inflammatory markers and resistance to erythropoietin-stimulating agents (ESAs). Methods: After a 1-month run-in period of standard bicarbonate dialysis with a synthetic membrane, 62 patients of both genders, and older than 18 years, dialysis vintage 48 ± 27 months, BMI 22 ± 3 (from 13 different dialysis units) were randomized (A-B or B-A) in a cross-over design to Vit E PS (treatment A) and to PS (treatment B) both for 6 months. C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations were determined by a sandwich enzyme immunoassay at baseline and every 2 months; red blood cell count, ESA dose and ESA resistance index (ERI) were assessed monthly. Results: Hemoglobin (Hb) levels significantly increased in the Vit E PS group from 11.1 ± 0.6 g/dl at baseline to 11.5 ± 0.7 at 6 months (p < 0.001) and remained unchanged in the PS group. Although ESA dosage remained stable during the observation periods in both groups, ERI was significantly reduced in the Vit E PS group from 10.3 ± 2.2 IU-dl/kg/g Hb week at baseline to 9.2 ± 1.7 at 6 months (p < 0.001). No significant variation of ERI was observed in the PS group. A significant reduction in plasma CRP and IL-6 levels was observed in the Vit E PS group: CRP from 6.7 ± 4.8 to 4.8 ± 2.2 mg/l (p < 0.001) and IL-6 from 12.1 ± 1.4 to 7.5 ± 0.4 pg/ml (p < 0.05). In the PS group, CRP varied from 6.2 ± 4.0 to 6.4 ± 3.7, and IL-6 from 10.6 ± 2.1 to 9.6 ± 3.5 (p = n.s.). Conclusions: Treatment with Vit E PS membranes seems to lead to a reduction in ESA dosage in HD patients; in addition, a low chronic inflammatory response may contribute to a sparing effect on exogenous ESA requirements.

Chronic inflammation may play an important role in early morbidity and mortality in hemodialysis (HD) patients. Interleukin-6 (IL-6) production is enhanced in long-term HD patients and this activated phase response has been shown to be a predictor of cardiovascular disease in the uremic syndrome as well as in the general population. Furthermore, IL-6 and C-reactive protein (CRP) have been negatively related to low serum albumin levels (MIA syndrome). Several studies have attempted to address the question as to whether the type of the dialysis membrane, the quality of the dialysate, and the dialysis technique may be responsible for the induction of a chronic inflammatory state. Recently, the Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown that high-efficiency hemodiafiltration (HDF)- treated patients had a better survival than HD-treated patients accounting for sex, dialysis dose, co-morbid condition and country specificities. Here we report data from the RISCAVID study, an observational and prospective trial including the whole chronic HD population in the north-west part of Tuscany (1,235 million people). The aim of the study was to elucidate the relevance of traditional and non-traditional risk factors on mortality and morbidity in HD patients as well as the impact of different HD modalities. Data at 30 months from this study showed the synergic effect of CRP and pro-inflammatory cytokines as the strong predictors of overall and cardiovascular mortality. HDF was associated to an improved cumulative survival independently of dialysis dose.

The endogenous inhibitor of nitric oxide (NO) synthase, asymmetric dimethylarginine (ADMA), is a strong cardiovascular (CV) risk marker in patients with chronic renal insufficiency. Statins have pleiotropic effects and are currently considered as potential ADMA-lowering agents.We investigated the effect of simvastatin on plasma ADMA levels in 35 patients with chronic kidney disease (CKD) by performing a secondary analysis of a randomized double-blind placebo-controlled trial where patients were randomized to receive simvastatin or placebo for 6 months.Plasma ADMA was higher in CKD patients (0.84 +/- 0.14 micromol/L) than in healthy subjects (0.69 +/- 0.10 micromol/L) (p0.001). In CKD patients, ADMA at baseline was related directly with triglycerides (r=0.42, p=0.01) and inversely with HDL cholesterol (r=-0.37, p=0.03) and creatinine clearance (p=0.03). As expected, simvastatin caused significant reductions in total cholesterol, LDL cholesterol and triglycerides, as well as in C-reactive protein (CRP; -28%, p=0.001) and IL-6 (-20%, p=0.05) but failed to decrease plasma ADMA both in crude and adjusted analyses.Simvastatin does not modify plasma ADMA. Because raised ADMA is known to prevent the favorable effect of statins on myocardial blood flow, cointerventions aimed at lowering or antagonizing ADMA may either prompt or potentiate the cardiovascular protective effect of simvastatin.

Chronic inflammation may play an important role in early morbidity and mortality in hemodialysis (HD) patients. Interleukin-6 (IL-6) production is enhanced in long-term HD patients and this activated phase response has been shown to be a predictor of cardiovascular disease in the uremic syndrome as well as in the general population. Furthermore, IL-6 and C-reactive protein (CRP) have been negatively related to low serum albumin levels (MIA syndrome). Several studies have attempted to address the question as to whether the type of the dialysis membrane, the quality of the dialysate, and the dialysis technique may be responsible for the induction of a chronic inflammatory state. Recently, the Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown that high-efficiency hemodiafiltration (HDF)- treated patients had a better survival than HD-treated patients accounting for sex, dialysis dose, co-morbid condition and country specificities. Here we report data from the RISCAVID study, an observational and prospective trial including the whole chronic HD population in the north-west part of Tuscany (1,235 million people). The aim of the study was to elucidate the relevance of traditional and non-traditional risk factors on mortality and morbidity in HD patients as well as the impact of different HD modalities. Data at 30 months from this study showed the synergic effect of CRP and pro-inflammatory cytokines as the strong predictors of overall and cardiovascular mortality. HDF was associated to an improved cumulative survival independently of dialysis dose.

Although several registries collecting data of patients with kidney diseases exist, only a few specifically collect data relating to renal biopsy. Kidney biopsy has been performed routinely in Pisa since 1977; the aim of this study was to report the relative frequency of nephropathies according to gender, age at time of biopsy, clinical presentation and renal function, based on histological diagnoses during the years 1977 through 2005. During this time, 3,810 kidney biopsies were performed, of which 89.3% were from native (n=3,446) and 10.7% from transplant kidneys. Throughout this period, 5% of renal biopsies were not diagnostic, so in this paper we report data regarding 3,269 native kidney nephropathies.During the years 1977 through 2005, data for renal biopsies were collected on specific registers filled out by clinicians. Information collected in the database included a variety of indicators, such as clinical anamnesis, creatinine clearance, daily proteinuria, hemoglobin levels, blood pressure, height and weight, clinical presentation, and current medications. Clinical presentation was defined as urinary abnormalities (UA), nephrotic syndrome (NS) and acute nephritic syndrome (ANS). Renal diseases were divided into 4 major categories: primary glomerulonephritis (GN), secondary GN, tubulointerstitial nephropathies (TIN) and vascular nephropathies (VN).From 1977 up to 1987, a mean of 95 +/- 18 renal biopsies/year were performed; this number significantly increased to 185 +/- 22 renal biopsies/year (range 138-200) (p0.001) in the following period (1988-2005). Renal biopsy was more frequently performed in males (59%) compared with females (41%). Of all diseases of the native kidney, primary GN was the most frequent (66%), followed by secondary GN (25.6%), TIN (4.2%) and VN (4.2%). The type of primary GN with the highest frequency was mesangial GN (both IgA and non-IgA) (45.7%), followed by membranous GN (23%), focal segmental glomerulosclerosis (19.8%), minimal change disease (5.3%), crescentic GN (4.2%) and postinfectious GN (2%). In terms of age, renal biopsy was more frequently performed in patients aged 20 to 60 years, and nearly 60% of patients presented a glomerular filtration rate (GFR)60 ml/min at the time of biopsy. The main clinical reason for performing renal biopsy was UA, in all the types of nephropathies.We confirm data that renal diseases are more frequent in men, with the exception of secondary GN. The mean age at diagnosis was 42 years resulting from the tendency not to perform renal biopsies in children and in elderly patients. Renal biopsy was mainly performed in patients with GFR60 ml/min and asymptomatic urinary abnormalities suggesting concern on the part of clinicians regarding glomerular diseases. The tendency to perform renal biopsies has been significantly increasing throughout our follow-up period.

BACKGROUND HFR [double chamber haemodiafiltration (HDF) with reinfusion of regenerated ultrafiltrate] is a novel dialytic method which combines the processes of diffusion, convection and adsorbance. In this technique an adsorbent cartridge of resin and charcoal may regenerate the ultrafiltrate suggesting its use as an endogenous substitution fluid. The aim of this multicentre randomized cross-over study was to compare HFR to online HDF in terms of inflammatory and nutritional parameters. METHODS After a 1 month run-in period of standard bicarbonate dialysis (HD) with a synthetic membrane, 25 chronic dialytic patients were randomized (A-B or B-A) to be treated by HFR (A) with a two-chamber filter (SG 8 Plus - high permeability Polysulphone HF 0.7 m2 + SMC 1.95 sqm; Bellco, Mirandola, Italy) or by online sterile bicarbonate HDF. Each study period of 4 months was separated by 1 month of HD and the entire length of the study was 10 months. CRP levels were measured by a highly sensitive nephelometric assay (Dade, Behring) with a sensitivity of 0.1 microg/ml. Cytokine concentrations were determined by EIA [Interleukin (IL) 6, Biosource, USA and IL-10 Bender MED-Systems, Vienna]. The sensitivity thresholds were < 5 pg/ml for IL-6 and < 8 pg/ml for IL-10. Serum leptin was determined with a ELISA method (Biosource, USA). All parameters were determined monthly in patients starting a midweek dialytic session. RESULTS Plasma CRP and IL-6 were significantly reduced during the 4 months of HFR and HDF: CRP from 8.0 +/- 3.2 to 5.6 +/- 3.4 mg/l with HFR (P < 0.05) and from 9.4 +/- 4.3 to 5.9 +/- 3.9 mg/l with HDF (P < 0.05). IL-6 decreased from 14.8 +/- 6.3 to 10.1 +/- 3.2 with HFR (P < 0.02) and from 12.1 +/- 4.2 to 9.6 +/- 3.7 with HDF (P = ns) with a percentage decrease after 4 months of 32% with HFR vs 21% with HDF. During the 1 month wash-out period with HD, CRP increased from 5.7 +/- 3.6 to 8.7 +/- 3.9 mg/l (P < 0.01) and IL-6 from 10 +/- 3.4 to 13.5 +/- 5.2 pg/ml (P < 0.01). A significant increase in IL-10 was detected either in HFR (from 4.8 +/- 2.1 to 6.89 +/- 1.7 pg/ml) and in HDF (from 3.3 +/- 1.7 to 8.95 +/- 4.3 pg/ml; P < 0.05) after 4 months. No significant variation in serum leptin levels were observed during the study. CRP and IL-6 were highly correlated (r = 0.54; P < 0.001) as was serum albumin and prealbumin (r = 0.39; P < 0.001). Serum albumin was negatively correlated with CRP (r = -0.26; P < 0.01) and IL-6 (r = -0.19; P < 0.05); serum prealbumin was correlated with IL-6 (r = 0.37; P < 0.001) and with CRP (r = 0.24; P < 0.01). CONCLUSIONS Haemodiafiltration with online regeneration of ultrafiltrate and online HDF are highly biocompatible techniques and no significant difference between HFR and online HDF was observed in terms of reduction of inflammatory markers. Further studies with a longer follow-up are needed to evaluate the clinical relevance of the online endogenous reinfusion to counteract the chronic inflammatory state of the uraemic patient.

Background. The beneficial effects of statins in reducing cardiovascular events have been attributed predominantly to their lipid-lowering effects, recent studies suggest that these effects might be due to their anti-inflammatory properties. We here investigate the in vivo and in vitro effects of simvastatin on cytokine production in pre-dialysis chronic renal failure patients. Methods. Our clinical study has been designed as a randomized double-blind placebo controlled study. A total of 55 chronic kidney disease (CKD) patients at stages 3 and 4 (mean creatinine clearance 45 ml/min, range 15-60) were randomly assigned to receive simvastatin 40 mg/day or placebo, added to their ongoing treatment, for 6 months. Blood samples were obtained at baseline, and after 3 and 6 months of observation for the determination of lipids, inflammatory markers and renal function. For the in vitro studies, the effect of increasing doses of simvastatin on cytokine production [namely interleukin (IL)-6 and IL-8] in human cultured monocytes from 10 healthy subjects (HS) and 15 CKD patients stimulated by lipopolysaccharide (LPS) was investigated. Results. A significant reduction in total cholesterol from 221 ± 44 mg/dl to 184 ± 41 mg/dl (3 months) and to 186 ± 39 mg/dl (6 months) (P < 0.02) and low-density lipoprotein cholesterol from 139 ± 40 mg/dl to 104 ± 29 mg/dl (3 months) and to 100 ±31 mg/dl (6 months) (P < 0.001) was observed in the 28 patients treated with simvastatin. In this group, C-reactive protein (CRP) levels significantly decreased from 2.6 mg/l [interquartile range (IQR 4.9)] to 2.0 mg/l (IQR 1.9) (P= 0.03) at 6 months (P < 0.05). A parallel reduction of IL-6 levels from 5.1 pg/ml (IQR 3.8) to 3.5pg/ml (IQR 3.1) (P=0.001) at 6 months was also observed. No significant reduction in inflammatory markers [CRP from 5.1 mg/l (IQR 1.9) to 5.4mg/l (IQR 1.3) (P=NS) at 6 months] or plasma lipids [LDL-cholesterol from 127 ± 32 mg/dl to 131 ± 21 mg/dl (6 months)] was observed in the 27 patients of the placebo group. In the in vitro studies, the average value for cell-associated IL-6 and IL-8 was higher in CKD (155 ± 95 pg/ml monocytes for IL-6 and 722 ± 921 pg/ml monocytes for IL-8) vs HS (137 ± 87 pg/ml monocytes and 186 ± 125pg/ml monocytes) (P < 0.01) and was not affected by simvastatin alone. LPS resulted in a significant increase in cytokine production (IL-6: 1954 ± 321 pg/ml monocytes for CKD and 1451 ± 237 pg/ml monocytes for HS; P < 0.001); the simultaneous addition of increasing doses of simvastatin to these cultures induced a dose-dependent inhibition of IL-6 and IL-8 production in stimulated peripheral blood mononuclear cells in all groups. Conclusions. These results indicate that simvastatin in commonly used doses has an in vitro and in vivo anti-inflammatory effect in CKD patients, and may play an important role in counteracting the mechanisms involved on the pathogenesis of cardiovascular disease.

In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and cardiovascular mortality. The aim of the present study was to evaluate CRP levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities and dialyzed with different membranes, at baseline and after 6 months. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 3 months and were prospectively followed in their initial dialytic modality for 6 months. Patients were treated with conventional bicarbonate dialysis (N = 127) or hemodiafiltration (N = 120). Patients treated with conventional bicarbonate dialysis were dialyzed with different membranes: Cuprophane (N = 51), low-flux cellulose modified membrane (N = 37) and synthetic membranes (N = 39). Hemodiafiltration was performed in post-dilution mode with polysulfone (N = 66) and polyacrylonitrile (N = 54) membranes. Analysis of baseline CRP values in the clinically stable patients showed that an unexpectedly high proportion (47%) of the patients had CRP values higher than 5 mg/l (upper limit in normal subjects). The mean +/- S.D. CRP values were significantly higher (P0.05) in hemodiafiltration with infusion volumes10 l per session (14.6+/-3.1 mg/l) than in standard hemodialysis (5.1 +/- 2.1 mg/l) and hemodiafiltration with infusion volumes20 l per session (4.9 +/- 2.1 mg/l). These values did not significantly change after 6 months of follow-up. Concerning the membranes, the highest levels of CRP were observed in patients dialyzed with Cuprophane with a significant increase from 15.1 +/- 3.6 to 21.2 +/- 3.1 mg/l after 6 months (P0.05); a significant reduction of CRP levels was observed in patients dialyzed with polysulfone in the same follow-up period (from 13.5 +/- 2.9 to 8.1 +/- 2.4 mg/l; P0.05). The CRP increase following low volume HDF can be related to back-filtration of bacterial derived contaminants.; moreover, an important effect on CRP of the hemodialysis membrane is observed and new synthetic membranes can be used to decrease these levels.

The most frequent cause of death in hemodialysis (HD) patients is cardiovascular disease (CVD), and chronic inflammation has been identified as an epidemiologically important risk factor for CVD. Elevated levels of minor acute phase reactants, such as ceruloplasmin (Cp) and transferrin, have been related to an increased cardiovascular risk in the general population, but little information is available regarding dialysis patients. We investigated the correlation between Cp and copper concentration (Cu) with major acute phase reactants such as C-reactive protein (CRP) and interleukin-6 (IL-6) in a population of chronic dialytic patients. Furthermore, we evaluated the relationship between long-lasting acute phase proteins such as Cp and nutritional markers.CRP (Berhing Diagnostic, high sensitivity modified nephelometric technique, detection limit 0.1 mcg/mL), IL-6 (EIA, RD Systems), serum albumin, prealbumin, Cp (Berhing, nephelometric assay), copper (mass spectrometry, Varian) and standard laboratory routine analysis were determined in 75 stable chronic dialysis patients (age 60 +/- 16 yrs; dialytic age 65 +/- 50 months ) starting a midweek dialytic session.Thirty-seven patients (49%) had clinical signs of cerebrovascular, cardiovascular or peripheral vascular disease. Fifty-one patients (67%) showed biochemical inflammation markers as suggested by elevated CRP levels (mean 12.4 mg/L, SD 11.5) and IL-6 (mean 21.3 pg/mL, SD 19.7) with a positive correlation (r=0.65; p0.001) between CRP and IL-6. CRP and IL-6 also related negatively to nutritional markers such as albumin and prealbumin (r=-0.42; p0.01). Cp related significantly to CRP (r=0.4; p0.001) and IL-6 (r=0.41; p0.001), and as expected to copper (r=0.96; p0.001), but not with serum albumin and prealbumin. In a multivariate logistic regression analysis, age (p0.001), dialytic age (p0.01), IL-6 (p=0.04) and Cp (p=0.02) were the strongest risk factors for cardio-vascular disease (CVD).These data suggest that serum Cp could be useful in monitoring the ""chronic inflamed"" patient and support the suggestion that elevated metalloprotein levels are associated with an increased cardiovascular risk in a population of stable dialysis patients.

Secondary renal involvement in advanced non-Hodgkin’s lymphomas is quite common, but primaryrenal lymphoma (PRL) is a rare disease. It accountsfor 0.7% of all extra-nodal lymphomas in NorthAmerica and 0.1% in Japan, and 65 cases have beenreported in the worldwide literature. PRL is also adebated disease because kidneys do not containlymphatic tissue [1,2]. General agreement exists aboutthe criteria needed to define the diagnosis of PRL: (i)renal failure as the first presentation in the absence ofother causes of renal impairment; (ii) rapid improve-ment of renal function following therapy; (iii) increaseof the kidneys’ size without any urinary tract obstruc-tion; (iv) absence of other nodal or extra-nodalinvolvement; and (v) definite diagnosis made by histo-logical examination.The medianageat PRL diagnosis is 64years, andthediseaseismorefrequentinmalesthaninfemales. Acuterenalfailure,flankpainanddetectionofarenalmassarethe most frequent manifestations [3]. Renal failure mayresult from a large variety of causes, such as lympho-matousinfiltrationofrenaltissueorhypercalcaemia[4].Histological examination is mandatory, as clinical andradiological findings often evoke renal carcinoma [5].The prognosis is poor, but long-term survivors havebeen reported occasionally after surgical resection andcombination chemotherapy, in unilateral renal lym-phoma [2]. Bilateral renal involvement has a prevalenceof 43% [6]: in this case, the prognosis is very severe andchemotherapy is the usual proposed treatment becausesurgery has never been described (Table 1).We report a case of bilateral PRL successfullytreated by surgical resection leading to a three-quartersablation of native renal mass followed by combinationchemotherapy.