Factors related to the development of CMV-specific CD8+ T cell response in CMV-seropositive solid organ transplant candidates.

This cross-sectional study analyzes factors associated with the development of CMV-specific CD8+ response, measured by IFNg production after cytomegalovirus (CMV) peptide stimulation, in CMV-seropositive solid organ transplantation candidates. A total of 114 candidates were enrolled, of whom 22.8% (26/114) were nonreactive (IFNγ < 0.2 IU/mL). Multivariate logistic regression analysis showed that age, HLA alleles and organ to be transplanted were associated with developing CMV-specific CD8+ immunity (reactive; IFNγ ≥ 0.2 IU/mL). The probability of being reactive was higher in candidates over 50 than in those under 50 (OR 6.33, 95%CI 1.93-20.74). Candidates with HLA-A1 and/or HLA-A2 alleles had a higher probability of being reactive than those with non-HLA-A1/non-HLA-A2 alleles (OR 10.97, 95%CI 3.36-35.83). Renal candidates had a higher probability of being reactive than lung (adjusted OR 8.85, 95%CI 2.24-34.92) and liver candidates (OR 4.87, 95%CI 1.12-21.19). The AUC of this model was 0.84 (p < 0.001). Positive and negative predictive values were 84.8% and 76.9%, respectively. In renal candidates longer dialysis was associated with an increased frequency of reactive individuals (p = 0.040). Therefore, although the assessment of CMV-specific CD8+ response is recommended in all R+ candidates, it is essential in those with a lower probability of being reactive, such as non-renal candidates, candidates under 50 or those with non-HLA-A1/non-HLA-A2 alleles.

Compliance with mineral metabolism targets in haemodialysis patients: moving backwards?

BACKGROUND: To standardize therapy and improve the clinical outcome for chronic haemodialysis (HD) patients, guidelines have been developed for mineral metabolism management. We evaluated compliance with different mineral metabolism guidelines. METHODS: 2,951 chronic HD patients from 61 dialysis centres in Spain were studied. Mineral metabolism management data from a 1-year period were analysed according to KDOQI, KDIGO, and Spanish guidelines. RESULTS: Only 1% (KDOQI), 6% (KDIGO) and 11% (Spanish guidelines) of patients continuously achieved total calcium (Ca), phosphate (P) and parathyroid hormone (PTH) target-range values during the year with higher percentages if we considered the 1-year average. The yearly Ca, P and iPTH average accomplished Spanish guidelines with different percentage among centres: CA 62-100%, P 59-91%, PTH 61-89%, and 28-77% considering all three targets together. The KDIGO guidelines recommend similar percentages except for P (33-77%). No differences were found related to eKt/V, online haemodiafiltration/HD, weight, body mass index, or dialysis vintage. They were only related to age, blood flow, effective treatment time, and dialysate calcium but without relevant clinical differences. Patients outside the target ranges generated significantly higher treatment costs. CONCLUSIONS: Compliance with mineral metabolism targets in HD patients was poor and showed a wide variation between treatment centres.

[Acetate-free on-line PHF: how to improve hyperacetatemia and haemodynamic tolerance]. / PHF on-line sin acetato: cómo mejorar la hiperacetatemia y la tolerancia hemodinámica.

SUMMARY BACKGROUND: The small quantity of acetate present in the dialysis fluid exposes patient's blood to an acetate concentration 30-40 times the physiological levels. This amount is even greater in hemodiafiltration on-line. Our purpose was to evaluate the clinical-analytical effects using three different dialysis techniques in the same patient. METHODS: 35 patients on hemodialysis were included. All patients were treated with conventional bicarbonate dialysate for 3 months, after randomization were switched to first be treated with PHF online with standard bicarbonate dialysate for 6 months and then switched to PHF on-line acetate-free dialysate for the other 6 months or to invert the two last periods. Blood samples were drawn monthly throughout the study and clinical data were obtained. RESULTS: Postdialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate with respect to the period of PHF with free-acetate dialysate. Moreover, the percentage of patients with postdialysis blood acetate levels in the pathologic range was higher in patients treated with conventional bicarbonate dialysate respect to PHF on-line acetate-free dialysate period (61% vs. 30%). Serum concentrations of chloride postdialysis were higher and serum concentrations of bicarbonate pre and posthemodialysis were lower in the PHF free-acetate period. The incidence of hypotensive episodes was significantly lower in the PHF on-line with conventional dialysate. CONCLUSIONS: PHF on-line with free-acetate dialysate allows that most of patients finished hemodialysis with blood acetate levels in the physiologic ranges. PHF on-line is a predilutional hemodiafiltration treatment with better tolerance than hemodialysis with standard bicarbonate dialysate.

PHF on-line sin acetato: cómo mejorar la hiperacetatemia y la tolerancia hemodinámica / No disponible

Antecedentes: la presencia de acético en el Líquido de Diálisis (LD) expone al paciente a una concentración de acetato 30-40 veces superior a la normal. Dicha exposición aumenta en técnicas de Hemodiafiltración (HDF) online. El objetivo de dicho estudio fue evaluar los cambios clínico-analíticos al usar tres técnicas de Hemodiálisis(HD) diferentes. Métodos: se reclutaron 35 pacientes en HD estable. Se dializaron tres meses con HD convencional y luego fueron aleatorizados para pasar a una técnica de PHF on-line con concentrado convencional seis meses, y después pasaron a PHF on-line sin acetato otros seis meses. El otro grupo invertía estos dos períodos. Se obtuvieron análisis de sangre y datos clínicos de HD. Resultados: las medias de los acetatos posdiálisis fueron significativamente superiores durante los períodos de tratamiento con acético respecto al período sin acetato. El porcentaje de valores patológicos de acetato posdiálisis fue significativamente superior durante los períodos de tratamiento con acético (61 respecto al 30%). Las concentraciones de cloro pos-HD fueron superiores y las de bicarbonato pre y pos-HD fueron menores durante el período sin acético. El número de hipotensiones fue significativamente inferior en el período de PHF on-line con LD estándar respecto a los otros períodos. Conclusiones: la técnica de PHF on-line sin acetato disminuye la exposición a concentraciones elevadas de acetato y consigue que la mayoría de pacientes termine la HD con una acetatemia en el rango fisiológico. La PHF on-line es un tratamiento de HDF predilucional con mejor tolerancia que la HD estándar con bicarbonato (AU)

Summary Background: the small quantity of acetate present in the dialysis fluid exposes patient’s blood to an acetate concentration 30-40 times the physiological levels. This amountis even greater in hemodiafiltration on-line. Our purpose was to evaluate the clinical-analytical effects using three different dialysis techniques in the same patient. Methods: 35 patients on hemodialysis were included. All patients were treated with conventional bicarbonate dialysate for 3 months, after randomization were switched to first be treated with PHF online with standard bicarbonate dialysate for 6 months and then switched to PHF on-line acetate-free dialysate for the other 6months or to invert the two last periods. Blood samples were drawn monthly throughout the study and clinical data were obtained. Results: Posdialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate with respect to the period of PHF with free-acetate dialysate. Moreover, the percentage of patients with posdialysis blood acetate levels in the pathologic range was higher in patients treated with conventional bicarbonate dialysate respect to PHF on-line acetate-free dialysate period (61% vs. 30%). Serum concentrations of chloride posdialysis were higher and serum concentrations of bicarbonate pre and poshemodialysis were lower in the PHF free-acetate period. The incidence of hypotensive episodes was significantly lower in the PHF on-line with conventional dialysate. Conclusions: PHF on-line with free-acetate dialysate allows that most of patients finished hemodialysis with blood acetate levels in the physiologic ranges. PHF on-line is a predilutional hemodiafiltration treatment with better tolerance than hemodialysis with standard bicarbonate dialysate (AU)

C-reactive protein and low albumin are predictors of morbidity and cardiovascular events in chronic kidney disease (CKD) 3-5 patients.

BACKGROUND: Overall and cardiovascular mortality are significantly higher in hemodialysis patients with elevated C-reactive protein (CRP). The aim of this study was to determine whether CRP is a marker of overall and cardiovascular morbidity in chronic kidney disease (CKD) 3-5 patients. METHODS: 90 chronic kidney disease 3-5 patients were prospectively followed during a period of 24 months. Cardiovascular events were defined as episodes of myocardial infarction, stroke, angina pectoris and/or peripheral vascular disease. Morbidity was analyzed in terms of both the need for hospital admission (> 48 h) and total number of days of hospitalization during the follow-up period. CRP was stratified into tertiles of low (< 8 mg/l), medium (8-10.5 mg/l) and high (> 10.5 mg/l). The use of some drugs such as ACE inhibitor and ARAII were also recorded. RESULTS: During the follow-up period, 23 patients (25%) required hospital admission. New cardiovascular events were observed in 20 patients (22%), 10 patients died during the follow-up. Adjusted Cox regression analysis revealed that CRP and serum albumin significantly predicted the risk of cardiovascular events. Similarly, high CRP, low serum albumin and low hemoglobin levels predicted morbidity as measured by the number of hospitalizations. Hemoglobin and albumin levels were lower in patients with high CRP (> or = 10.5 mg/l, highest tertile) as compared with low CRP levels (< or = 8 mg/l, lowest tertile). Patients receiving treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor Type 1 antagonist (ARA-II) had significantly lower levels of CRP than those who were not under such treatment (n = 46, CRP = 8.7 (5.1-29.8) vs n = 44, CRP = 10.4 (6.1-37.2), p < 0.05) (Figure 1). CONCLUSIONS: Our results show that CRP and low albumin, markers of inflammation, predict cardiovascular events and morbidity in CKD 3-5 patients before initiation of chronic hemodialysis.

Anemia associated with pegylated interferon-alpha2a and alpha2b therapy in hemodialysis patients.

AIMS: Anemia is a well-known side effect of interferon therapy since interferons are potent inhibitors of erythropoiesis. The aim of this study was to compare the anemia associated with pegylated interferon (PEG-IFN) (alpha2a versus alpha2b therapy in hemodialysis patients (HD) with chronic hepatitis C. METHODS: In order to study the anemia, doses of erythropoietic growth factors (EGF), hemoglobin (Hb) and erythropoietin resistance index (ERI) were compared at baseline and after PEG-IFN-alpha2a or alpha2b therapy in 16 HD patients with chronic C hepatitis. Pharmacokinetic studies were performed in 4 of those treated with PEG-IFN-alpha2b and 2 patients treated with PEG-IFN-alpha2a. Secondary end-points were viral response and serious adverse events. RESULTS: At 4-6 months after the beginning of therapy, both PEG-IFN-alpha induced a significant increment in the erythropoietin resistance index. This increment was significantly higher in patients treated with PEG-IFN-alpha2a when compared with alpha2b (45 vs 9.9, p = 0.012). The pharmacokinetics of PEG-IFN-alpha2a and alpha2b in HD patients were different, the C(max), C(min) and the area under the serum concentration time curve, were all higher in patients treated with PEG-IFN-alpha2a compared with PEG-INF-alpha2b. Discontinuation of therapy occurred in 2 (28.5%) of the 7 patients in the PEG-IFN-alpha2a group and in 4 (44%) of the 9 patients in the PEG-IFN-alpha2b group. Three (42%) subjects in the alpha2a group and 5 (55%) in the alpha2b group had a response at the end of the 48 weeks of therapy. In 4 (44.4%) of the 9 patients treated with alpha2b the viral response was sustained. CONCLUSIONS: In summary, patients treated with PEG-IFN-alpha2a have a major inhibitory effect on erythropoiesis. This could be explained by the different pharmacokinetic properties of PEG-IFN-alpha2a and alpha2b. Further studies are needed to clarify how these findings influence the efficacy, safety and cost-effectiveness of the PEG-IFN-alpha2.

Microinflammation induces endothelial damage in hemodialysis patients: the role of convective transport.

Cardiovascular complications are a major cause of mortality in hemodialysis patients. On-line hemofiltration combines convective clearance for removing large solutes with diffusion to remove small solutes and is associated with a significant reduction of inflammation and improved patient survival. We compared on-line hemofiltration to high-flux hemodialysis (HF-HD) in patients in a sequential manner. At baseline, 15 stable patients on HF-HD as compared with five control subjects showed significant increases in CD14+CD16+ cells, endothelial microparticles, and endothelial progenitor cells (EPCs). After 4 months of on-line hemofiltration, the number of CD14+CD16+ cells, microparticles, and EPCs decreased. After returning to HF-HD for 4 months, all measured parameters returned to their respective baseline values. The number of CD14+CD16+ cells correlated with both endothelial microparticles and EPCs. We conclude that on-line hemofiltration attenuates endothelial dysfunction possibly by decreasing microinflammation. This effect may be directly caused by a modulatory effect of on-line hemofiltration on proinflammatory cells or by a complex interaction that encompasses a wider removal of uremic toxins.

Sleep disorders are underdiagnosed in patients on maintenance hemodialysis.

BACKGROUND: Sleep apnea-hypopnea syndrome (SAHS) is a cardiovascular risk factor. The aim of this study was to evaluate sleep disorders using polysomnography on a non-selected population of patients on maintenance hemodialysis. METHODS: Overnight polysomnography was performed on 32 hemodialysis patients (24 men/8 women, 54 +/- 16 years), and on 19 healthy subjects of similar age, sex and body mass index who were used as controls. RESULTS: In hemodialysis patients, the most frequent sleep disorder was SAHS in 44% (14/32), followed by insomnia in 41% (13/32). Compared to healthy controls, patients on hemodialysis showed less slow-wave sleep and rapid eye movement sleep (23 vs. 36%, p = 0.001), less sleep efficiency (71 vs. 87%, p = 0.0079) and a higher periodic limb movement index (39.7 vs. 9.1; p = 0.003). An increase in apnea-hypopnea index (18.9 vs. 4.3; p = 0.007) and dips in the SaO(2) (> or =4%) per hour of sleep (22.6 vs. 6.4; p = 0.021) were also significantly greater in hemodialysis patients than controls. 72% of the cases of SAHS were diagnosed solely by means of polysomnography. CONCLUSIONS: The patients on hemodialysis showed poor sleep quality with a significant increase in the apnea-hypopnea index and in the number of dips in SaO(2). SAHS was underdiagnosed in a large percentage of the hemodialysis patients.

Antibody-mediated pure red-cell aplasia (PRCA): the Spanish experience.

BACKGROUND: The incidence of antibody (Ab)-mediated pure red-cell aplasia (PRCA) in patients with chronic kidney disease (CKD) has increased between 1998 and 2002. After initially responding to treatment with recombinant human erythropoietic agents for CKD-associated anemia, patients became treatment-refractory and severely anemic. Although most PRCA cases have occurred in Europe, the varying epidemiologies among individual countries have not been well characterized. METHODS: We investigated Ab-mediated PRCA in 12 Spanish patients treated with epoetin alfa alone or prior to treatment with epoetin beta (n=1) or darbepoetin alfa (n=1). Serum Abs against epoetin alfa were detected by radioimmunoprecipitation (RIP) assay or bioassay. Following diagnosis of PRCA, erythropoietic treatment was stopped and patients received immunosuppressive therapy alone (n=11) or in combination with renal transplant (n=1). RESULTS: Treatments were administered for 16 months (average) before diagnosis of PRCA in bone marrow aspirates (n=8) or biopsies (n=4). At diagnosis, patients had an average of 0.68% blood reticulocytes and blood hemoglobin (Hb) level of 7.13 g/dL. Eight patients had anti-epoetin Abs detected by RIP, and 5 had neutralizing Abs measured in the bioassay. As of December 2003, 4 patients had died, 3 had no recovery, and 5 had recovered from anemia (blood Hb level, 9.9 g/dL). All 5 recovering patients received corticosteroid therapy alone, and 1 received a renal transplant as well as corticosteroids. CONCLUSIONS: Sudden onset of treatment-refractory anemia in CKD patients suggests a course of treatment cessation followed by diagnostic procedures for Ab-mediated PRCA, and immunosuppressive therapy. This study may serve as a model for a centralized global PRCA registry.

Multivariate analysis of factors associated with renal dysfunction in patients with obstructive jaundice.

BACKGROUND: The aim was to evaluate the factors determining preoperative renal dysfunction in patients with obstructive jaundice. METHODS: In a prospective cross-sectional observational study, 63 patients, 27 with benign and 36 with malignant obstructive jaundice, were investigated at admission and compared with 25 healthy control subjects. Variables analysed included extracellular body water (ECW) compartment, plasma levels of aldosterone, renin, atrial natriuretic peptide, vasopressin, nitric oxide, endothelin (ET) 1 and prostaglandin E2 (PGE2), urinary nitric oxide and PGE2, serum albumin and renal function. RESULTS: The metabolic profile of obstructive jaundice was characterized by a depletion of the ECW (P = 0.004), and increased plasma levels of atrial natriuretic peptide (P < 0.001), ET-1 (P = 0.044), vasopressin (P = 0.017), aldosterone (P = 0.005) and renin (P = 0.001). Increased plasma (P < 0.001) and urinary (P = 0.001) PGE2 levels were also found. Fifty-four per cent of patients had a creatinine clearance of less than 70 ml/min. In multivariate analysis, serum bilirubin, renin, ET-1, PGE2, decreased urinary sodium excretion and age were identified as predictors of renal dysfunction. CONCLUSIONS: Renal dysfunction in patients with obstructive jaundice was associated with the degree of biliary obstruction, age of the patient and reduced urinary sodium excretion. These alterations were closely related to derangements in sodium- and water-regulating hormones.

Randomized clinical trial of the effect of intravenous fluid administration on hormonal and renal dysfunction in patients with obstructive jaundice undergoing endoscopic drainage.

BACKGROUND: Renal dysfunction in patients with biliary obstruction is associated with extracellular water depletion. This study examined the effect of preoperative saline infusion before biliary drainage on hormonal and renal functional derangements in patients with obstructive jaundice. METHODS: In a randomized study, 49 patients with malignant obstructive jaundice were investigated at baseline, on the day of drainage, and at 24 h, 72 h and 7 days after internal endoscopic biliary drainage. Patients were randomized to receive (n = 22) or not to receive (n = 27) 3000 ml normal saline intravenously for 24 h before drainage. Variables analysed included extracellular water volume, creatinine clearance, and serum levels of aldosterone, renin, atrial natriuretic peptide (ANP), vasopressin and albumin. RESULTS: Preoperative saline infusion produced a rise in creatinine clearance, diuresis, ANP concentration and extracellular water volume but this did not translate into better recovery of renal function after operation. Drainage produced a fall in creatinine clearance in all patients, but hormonal and renal function had recovered by 2 days after restoration of bile flow, independently of preoperative hydration. CONCLUSION: Fluid administration expands the extracellular water compartment before drainage but fails to improve renal function after drainage. Definitive improvement in endocrine and renal function requires the restoration of bile flow into the duodenum.

Natural history of acute HCV infection in hemodialysis patients.

AIMS: Chronic liver disease develops in the majority of non-uremic patients with hepatitis C virus (HCV) infection. The aim of this study was to analyze the evolution towards chronic hepatopathy in 19 cases of acute hepatitis C observed in hemodialysis patients from 1990 to 2001. METHODS: A prospective follow-up study on HCV infection was conducted in 3 HD units from April 1990 to June 2001 to study clinical outcomes after acute hepatitis C. A total of 781 patients were tested monthly for alanine aminotransferase and anti-HCV in serum. In this period, 19 patients suffered from acute hepatitis C. Evolution to chronic liver disease in the follow-up was evaluated by means of biochemical (increased ALT) and virological criteria (HCV-RNA+). The transmission mechanism, the apparition of anti-HCV, clinical manifestations and mortality were also investigated. RESULTS: In 15 (78.9%) of the 19 patients, the viremia remained positive (chronic viremia) and 11 patients (57.8%) evolved to chronic liver disease (chronic viremia and high transaminase levels) with a median follow-up of 3 years (range 1 - 6). Five of them who underwent liver biopsies had histologic signs of chronic active hepatitis. One of them (5.2%) evolved to liver cirrhosis in the follow-up. In 4 out of 19 patients (21%) the HCV infection resolved. Although 7 (36.8%) of them died in the follow-up, acute hepatitis C infection was not a short-term independent risk factor of death. CONCLUSIONS: Three years after acute hepatitis C, 87.5% of the hemodialysis patients remained HCV-RNA positive and 56.2% evolved to chronic liver disease. It is important to stress that HCV infection spontaneously cleared in 4 out of 19 patients (21%).

Role of adhesion molecules in mononuclear cell apoptosis induced by cuprophan hemodialysis membranes.

BACKGROUND/AIM: Hemodialysis with Cuprophan (CU) membranes induces mononuclear cell activation, leading to increased expression of adhesion molecules, formation of cell aggregates, and apoptosis. It is likely that structure(s) of the CU membrane interact with mononuclear cell surface molecules which transduce biochemical signals to the cell. Interactions between adhesion molecules and extracellular matrix have been implicated in cell activation, proliferation, and/or apoptosis. In the present work, we study whether adhesion molecules may be involved in CU-induced mononuclear cell aggregation and/or apoptosis. METHODS: The present study was performed using THP-1 cells, a human monocytic cell line, cultured in the presence of the CU membrane. CD11b and CD54 expression was studied with fluorescent monoclonal antibodies. Cell aggregation was quantified using a phase-contrast microscope. Apoptosis was evaluated by either light microscopy or annexin V labeling. RESULTS: The results show that incubation of CU membranes with the proteins CD11b, CD18, and CD54 or the blockade of these cell surface molecules with specific monoclonal antibodies inhibited the CU-induced aggregation and apoptosis in a dose-dependent manner. CONCLUSION: These results suggest that CU membranes interact selectively with these specific proteins to induce cell activation which ultimately results in apoptosis.

Assessment of the length of each hemodialysis session by on-line dialysate urea monitoring.

Hemodialysis (HD) prescription is usually based on the periodical measurement of the Kt/V achieved in a midweek dialysis session. The purpose of the study was to assess the duration of each HD session to achieve a target dose of dialysis. This allowed to determine whether a given dialysis session may be considered representative of the other HD sessions. Seventy-two HD sessions were studied in 4 stable patients, who were randomly dialyzed during 3 consecutive periods, each lasting 2 weeks, using a different blood flow rate (Qb) in each period: 400, 300 or 200 ml/min. All HD were prolonged to achieve an on-line dialysate urea monitor (UM) Kt/V of 1.2. The UM Kt/V was compared with the Kt/V calculated using pre-HD, post-HD and rebound (45 min post-HD) plasma water urea concentrations. Comparison of the duration of the second midweek dialysis session with the length of the other HD showed 95% concordance intervals (+/-2 SD) of +/-21.08 min for Qb 400, +/-26.88 min for Qb 300 and +/-37.02 min for Qb 200 ml/min. The 95% concordance intervals for whole body urea clearance were +/-32.0, +/-20.36 and +/-15.62 ml/min for Qb 400, 300 and 200 ml/min, respectively. No differences were observed between UM Kt/V and blood-based double-pool Kt/V obtained by the second-generation Daugirdas (1.18 +/- 0.08) and Garred (1.19 +/- 0.08) Kt/V formulas. In conclusion, a great variability was observed between different HD sessions with regard to the whole body urea clearance and the time required to attain a target Kt/V even when the HD characteristics remained constant. The length of every HD required to achieve a target dose of dialysis can be assessed by on-line dialysate urea monitoring.

Risk of death and liver cirrhosis in anti-HCV-positive long-term haemodialysis patients.

BACKGROUND: Hepatitis C virus (HCV) infection is the most common cause of chronic liver disease in haemodialysis patients. The aim of this study was to assess the impact of HCV infection on patient survival in a cohort of long-term haemodialysis patients and to evaluate the percentage of anti-HCV-positive patients that evolve to liver cirrhosis. METHODS: In 1992, 175 patients who had been on intermittent haemodialysis therapy for at least 6 months were included in the study (57 anti-HCV-positive and 118 anti-HCV-negative patients). Evaluation of patient outcome included date and cause of death, kidney transplantation, and the diagnosis of liver cirrhosis. Patient survival was estimated by the Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazards model was used to estimate the risk of death among dialysis patients who were anti-HCV positive. Other prognostic variables studied included age, gender, diabetes mellitus as cause of end-stage renal disease (ESRD), history of previous transplant, transplantation during follow-up, and time on haemodialysis treatment. The diagnosis of liver cirrhosis was made based on clinical and/or histological criteria. RESULTS: Eight-year patient survival in anti-HCV-positive subjects was lower (32%) than in anti-HCV-negative patients (52%) (log-rank, P=0.03). Four variables were found to be independent prognostic factors in patient survival: age (relative risk (RR) 1.04); diabetes as cause of ESRD (RR 3.6); transplantation during follow-up (RR 0.66) and presence of HCV antibodies (RR 1.62). The causes of death did not differ significantly between groups, except that four anti-HCV-positive patients died from liver disease. Ten (17.5%) of the 57 anti-HCV-positive patients were diagnosed to have liver cirrhosis at a median of 10 years after renal replacement therapy initiation and a median of 7 years after the first ALT level increase. CONCLUSION: In conclusion, our study shows an increased risk of death among long-term haemodialysis patients infected with HCV compared with non-infected patients. This might be partly explained by the high proportion of these patients that evolve to liver cirrhosis.

Blood pressure and body water distribution in chronic renal failure patients.

Evidence exists of the important role of sodium balance and extracellular fluid volume in the genesis of hypertension in chronic renal failure (CRF). Several studies have shown that patients with advanced CRF have an increased, interstitial and intravascular, extracellular water volume (ECW). The relationship between the increase in ECW and high blood pressure has also been reported. Using electric bioimpedance, body water distribution was studied in 32 patients from our dialysis unit. Twelve of these patients were hypertensive and 20 had normal blood pressure. Hypertensive patients had a significantly greater total body water volume and ECW than the normotensive patients. Given the importance of ECW in controlling blood pressure, one of the main aims of haemodialysis is a suitable extraction of sodium and water during the treatment. Despite technological advances in dialysis therapy, cardiovascular instability during treatment is still a clinical problem. In recent years, new strategies to control ECW, with good haemodynamic tolerance, have been developed. These strategies include haemofiltration, haemodiafiltration and sodium and ultrafiltration profiles.

Interferon therapy in hemodialysis patients with chronic hepatitis C virus infection induces a high rate of long-term sustained virological and biochemical response.

AIM: The aim of the present study was to analyze the efficacy and tolerance of interferon (IFN) therapy in hemodialysis (HD) patients with chronic hepatitis C virus (HCV) infection. Specifically, we assessed whether the "normalization" of serum ALT levels was associated with the disappearance of the HCV-RNA. METHODS: Thirteen hemodialysis patients with chronic hepatitis C were treated for one year with 3 MU of alpha-IFN. The primary end point was a sustained virological response defined as the absence of HCV-RNA in the last follow-up; the secondary end points were normalization of the serum ALT levels and histological improvement. ALT was considered "normal" below 27 IU/l. RESULTS: Ten patients completed the treatment, which was discontinued in the other 3 (23%). By the end of the treatment a virological response was observed in 8 of the 10 patients (80%) who completed the one-year IFN therapy. Biochemical response was associated with a virological response in 8 of the 9 patients in whom ALT levels became normal. Three patients had a biochemical and virological relapse in the follow-up. Two of them received a further year of IFN therapy, which resulted in a sustained biochemical and virological response. In all patients who underwent a liver biopsy (n = 5), the inflammation score improved. After a median follow-up of 5 years (range 2 - 7), a sustained response was observed in 6 (46%) of the 13 patients enrolled. Two patients with a sustained response received a kidney transplant and after more than 6 years still maintain a biochemical and virological response. Side effects included flu-like syndrome (n = 8), hemoglobin decrease (n = 8), thrombocytopenia (n = 3), depression (n = 1) and seizures (n = 1). CONCLUSION: IFN treatment over a one-year period produces a high rate of long-term virological response in HD patients, associated to a biochemical response in all cases.

Cardiovascular disease determinants in chronic renal failure: clinical approach and treatment.

INTRODUCTION: Cardiovascular disease (CVD), as the leading cause of morbidity and mortality in patients on renal replacement therapy (RRT), has a central role in everyday nephrological practice. METHODS: Consensus was reached on key points relating to the clinical approach and treatment of the main cardiovascular risk factors in RRT patients (hypertension, anaemia, hyperparathyroidism, dyslipidaemia, new emerging risk factors). In addition, the role of convective treatments on cardiovascular outcomes was examined. RESULTS: Hypertension should be managed by aiming at blood pressure values of < or =140/90 mmHg (< or =160/90 mmHg in the elderly), firstly by ensuring target dry body weight is achieved. No single class of drug has proved superior to others in RRT patients, provided that the blood pressure target is achieved, although ACE inhibitors have shown specific organ protection in high-risk patients (HOPE study) and are well tolerated. Anaemia should be managed by using erythropoietin and iron supplements, aiming at haemoglobin levels of 12 g/dl and keeping serum ferritin levels < 500 ng/ml. The management of hyperparathyroidism is currently unsatisfactory, as calcium supplements have the potential to increase cardiovascular calcification. While awaiting new calcium- and aluminium-free phosphate binders, it is essential to ensure dialysis adequacy. Clinical studies are in progress to assess the real impact of lipid-lowering drugs in RRT. In the meantime, serum LDL-cholesterol < 160 mg/dl and triglycerides < 500 mg/dl may be desirable targets. The impact of new emerging risk factors (inflammation and chronic infection, hyperhomocysteinaemia, metabolic waste-product accumulation) and their proper management are still under research. Convective dialysis treatments may confer some degree of protection from dialysis-related amyloidosis and mortality, but clinical data on this important issue are still controversial and no definitive conclusions can be drawn at present. CONCLUSION: CVD prevention and treatment is a great challenge for the nephrologist. Achieving evidence-based consensus can help in encouraging the implementation of best clinical practice in line with the progress of current knowledge.