Epidemiology of hepatitis D virus (HDV) infection in an urban area of northern Italy.

OBJECTIVES: The introduction of vaccination against hepatitis B initially reduced the number of HBV (hepatitis B virus) and HDV (hepatitis delta virus) infections, but the decreasing trend of HDV infection seems to have stopped. The aim of this study was to assess the prevalence of HDV infection in the general population living in the catchment area of Legnano Hospital in northern Italy. METHODS: Of the 22,758 subjects tested in 2007-2008, the 488 who were HBsAg (hepatitis B surface antigen)-positive [including 107 (21.9%) of non-Italian origin] were subsequently tested for anti-HDV antibodies. RESULTS: Of the 488 subjects who tested positive for HBsAg, 24 (4.9%) were anti-HDV positive, all aged between 30 and 60 years. The difference in prevalence between males (7.1%) and females (1.9%) was statistically significant (p < 0.05), but not that between Italian (5.0%) and non-Italian patients (4.7%). The differences in anti-HDV seropositivity between the patients with acute (0%) and chronic infections (6.3%), and between the incident (2.5%) and prevalent cases (7.4%), were not statistically significant, but there was a significant difference (p < 0.01) between those with asymptomatic (2.1%) and clinically symptomatic infections (10.3%). Intravenous drug abuse was the main source of infection. CONCLUSIONS: In the catchment area of our hospital, the prevalence of HDV infection does not seem to be due to patients of non-Italian origin, but to Italian patients who are not vaccinated against HBV and who survived the HDV epidemic of the 1970s and 1980s. Nevertheless, the increase in the number of immigrants from non-EU countries in recent years is soon likely to lead to a change in the epidemiology of HDV.

[From the SIN Mailing List: the use of hemodialysis after radiocontrast media administration in patients with chronic renal failure]. / Dalla Mailing-List soci SIN (ML-SIN). Il ruolo della dialisi nella nefropatia da mezzo di contrasto: dubbi e certezze.

Over the last few years there has been a progressive increase in percutaneous endovascular procedures in patients with chronic renal disease, due to the high incidence of vascular disease, particularly coronary artery disease, in this population. The use of contrast medium may further worsen renal function in such patients, in some cases even accelerating the progression towards end-stage renal failure, and increase patients morbidity and mortality. In this review we discuss the role of dialysis in preventing contrast-induced nephropathy and indications to its use in patients already on dialysis treatment undergoing diagnostic or therapeutic procedures with contrast medium injection.

Long term complete remission of severe nephrotic syndrome secondary to diffuse global (IV-G) lupus nephritis following autologous, haematopoietic peripheral stem (CD34+) cell transplantation.

Autologous haematopoietic stem cell transplantation has become an accepted powerful therapeutic procedure for patients with severe, intractable SLE. Here we describe a 26-year old patient with stage IV-G diffuse global proliferative lupus nephritis and refractory nephrotic syndrome who responded to autologous peripheral stem cell transplantation (ASCT) after two mobilization procedures. Five years later the patient is in complete clinical and immunologic remission. The indications for ASCT and its mechanism of action are briefly discussed.

Mechanisms and kinetics of the synthesis and release of platelet-activating factor (PAF) by polyacrylonitrile membranes.

Platelet-activating factor is a recognized mediator of anaphylaxis and bioincompatibility. Here, the mechanisms and the kinetics of the production of platelet-activating factor were studied in vivo during high-flux hemodialysis and in vitro in a recirculation model with polyacrylonitrile membranes, the AN-69 and the more recent SPAN, where the Na-metallilsulfonate group is partially substituted with the less polar methacrylate group. In in vivo studies, eleven patients were studied in cross over. Patients were randomly allocated to the AN-69 (5 patients) and to the SPAN membrane (6 patients) for two weeks. Measurements were made in the second week of use. After completion of the second week, the patients were switched to the other membrane for a further two weeks. Samples for leukocyte and platelet counts, PAF in whole blood or bound to platelets, the C3a des Arg and the C5b-C9 membrane attack complex as well as samples for clearances of urea, creatinine and phosphates were taken at different time intervals during treatment. PAF was detected by biological assay after methanol extraction of whole blood or of platelet pellets obtained by sequential centrifugation. C3a des Arg and the C5b-C9 fraction were detected by commercially available immunoassays. Results were analyzed by Minitab statistical package. PAF was detectable only during treatment with AN-69 but not with SPAN 1 min after start of the extracorporeal circulation in both whole blood (4.5 +/- 2.7 ng/ml) and on platelet surface (4.1 +/- 1.2 ng/ml). No statistical significant differences were observed between AN-69 and SPAN with regard to leukocyte and platelet counts, plasma C3a des Arg and C5b-C9 levels. The structure modification did not alter functional performances as indicated by the lack of statistically significant differences in clearance values between the two membranes. In in vitro experiments performed with normal washed and whole blood recirculated in a closed circuit demonstrated the presence of a plasma-dependent, complement-independent mechanisms responsible for the triggering of PAF synthesis and release with AN-69 but not SPAN membrane. PAF was extractable from the inner and outer side of both polyacrylonitrile membranes (AN-69: inner, 4.9 +/- 0.5 ng/ml; outer, 0.1 +/- 0.05 ng/ml; SPAN: inner, 5.5 +/- 0.6 ng/ml, outer: 3.3 +/- 0.7 ng/ml, SPAN vs. p < 0.001), suggesting that absorption may be relevant with both membranes.

Lymphocytic intracellular pH and Na+/H+ exchanger activity in hemodialysis patients.

We have evaluated intracellular pH (pHi) and Na+/H+ exchanger activity in peripheral lymphocytes from 16 patients on regular acetate hemodialysis. All the patients were taking oral NaHCO3 supplementation (30 mmol/day), to maintain predialysis arterial blood acid-base status within normal range (pH 7.36 +/- 0.02, PHCO3- 23.3 +/- 1.2 mM, pCO2 40.9 +/- 1.4 mm Hg). pHi was measured, using the fluorescent probe BCECF (2',7'-bis-carboxyethyl-5,6-carboxyfluorescein), both in nominal absence of bicarbonate (Hepes solution, pH 7.4; n = 10) and in the presence of HCO3-/CO2 buffer system (pH 7.4, [HCO3-] 25 mM, pCO2 40 mm Hg; n = 6). Predialysis pHi did not differ from controls when measured in the presence of HCO3-/CO2 (7.28 +/- 0.04 vs. 7.29 +/- 0.04, p = NS), but was lower in dialysis patients than in normal subjects (7.11 +/- 0.04 and 7.20 +/- 0.02, respectively; p < 0.05) when measured in Hepes solution. This suggested that bicarbonate-independent pHi regulation was abnormal in dialysis patients. To further characterize this abnormality of pHi regulation, lymphocytes were exposed to ethylisopropylamiloride, a specific Na+/H+ antiporter inhibitor, in Hepes solution; this maneuver induced a significantly lower decrement in pHi (0.04 +/- 0.04 vs. 0.15 +/- 0.03, p < 0.05) in dialysis patients than in controls, indicating reduced Na+/H+ exchanger activity in the patients. The rate of pHi recovery during the first 30 s after induction of various degrees of cell acidification (pHi range 6.2-7.0), which in the absence of HCO3-/CO2 is dependent on Na+/H+ exchanger activity, was also reduced in the patients as compared to controls (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Uremic inhibitors of erythropoiesis: a study during treatment with recombinant human erythropoietin.

The effects of increasing amounts of uremic sera (US) on the growth of erythroid progenitor cells [burst-forming unit erythroid (BFU-E)] collected from peripheral blood of normal subjects were evaluated to assess the potential role of uremic inhibitors of erythropoiesis during a treatment with recombinant human erythropoietin (r-HuEpo). US were collected from 8 patients on regular dialysis with marked anemia (Hb 6 +/- 0.5 g%) before and after a treatment with high doses of r-HuEpo (from 300 to 525 U/kg/week). Standard cultures for BFU-E were performed in alpha-metylcellulose with fetal calf serum (FCS) and 4 U/ml of r-HuEpo (Cilag, Ortho). In successive cultures, US were added at increasing amounts to the standard culture in order to assess a possible inhibitory effect on BFU-E growth. Finally, in order to assess a possible lack of stimulatory factors, we partially substituted FCS with US. The addition of US collected either before or after therapy with r-HuEpo to the standard culture had no effect on the growth of BFU-E. Vice versa, the number of cultured BFU-E decreased when FCS was partially substituted with US collected before r-HuEpo. This effect was not evident when FCS was partially substituted with US collected after r-HuEpo. No significant differences were recorded in the tested sera collected before and after therapy considering erythropoietin levels and amino acid levels. We hypothesized that some other factors with erythropoietic stimulatory activity (burst-promoting activity?) may be deficient in uremic patients with marked anemia and can be induced during therapy with r-HuEpo.

High-flux acetate haemodialysis: a single-centre experience.

One hundred haemodialysed patients have been treated for 4 h thrice weekly by acetate haemodialysis with high-flux dialysers (HAHD) 1.4-1.8 m2 and automated ultrafiltration control for 18.9 +/- 8.3 months. The aim of the study was to evaluate the efficacy of treatment as regards urea and beta 2-microglobulin removal, cardiovascular stability, acid-base balance and plasma Il-1 variations. Moreover medium-term observation of both lipid profile and basal beta 2-microglobulin concentrations were performed. With our current adequacy criteria (urea clearance greater than or equal to 120 l/week; KT/V greater than or equal to 1.2; beta 2-microglobulin removal greater than or equal to 150 mg/treatment), the occurrence of hypotension was 6% during 24,500 treatments. Cardiovascular stability was preserved by the increase of total peripheral resistances in response to cardiac output decrease. No disturbances of acid-base parameters were observed in spite of plasma acetate concentrations greater than 6 mmol/l. No variations of plasma Il-1 occurred during the session or 2 h later.

Erythrocyte ferritin in patients on chronic hemodialysis treatment.

Serum ferritin (SF) and erythrocyte ferritin (EF) were evaluated in 35 patients on chronic hemodialysis treatment (CHD), in 45 healthy subjects and in 22 nonnephropathic females with iron deficiency anemia. Twenty-five CHD patients with basal SF less than 500 micrograms/l were treated orally with 200 mg of Fe2+ for 2 months and the positive (hemoglobin increase greater than 1 g/dl) or negative response to the therapy was correlated to the basal levels of SF and EF. Three groups of CHD patients could be defined on the basis of their basal SF levels (hypo-, normo- or hyperferritinemic). Nine patients with increased SF levels had also EF levels significantly higher than the other CHD patients and controls since they were probably iron-overloaded. In the other 2 groups of CHD patients, EF levels were significantly higher than in controls for each level of SF probably because of the reduced utilization of iron by uremic bone marrow. Among the 25 treated CHD patients, only 5 responded to the therapy: 3 were hypoferritinemic while the other 2 responders had basal SF within the normal range. Four hypoferritinemic patients did not respond to the therapy. Four out of five responders had the lowest EF levels among CHD patients. EF measurement could be an important and useful test in detecting the presence of an iron deficiency erythropoiesis in CHD patients.

Is the dialysate fluid source of complement activating factors?

To distinguish between membrane-induced and dialysate-induced mechanism of complement activation attending hemodialysis (HD), the C3a plasma level and blood neutrophil count profiles have been determined during procedures performed with noncellulosic membranes, as PAN and PMMA (with minimal complement-activating potential) and, by comparison, with new cuprophane (that displays the greatest complement-activating potential). Furthermore, PAN and PMMA membranes have been used in 2 other blood purification methods: high efficiency hemofiltration (HEHF), in which there is no dialysate on the other side of the membrane, and hemofiltration without substitution fluid and with reinfusion of dialysis-regenerated hemofiltrate (HWSF), in which the dialysate is separated from the blood circuit by the hemofiltrate circuit. In addition, sequential dialysis-ultrafiltration (UFD) experiments with PAN membranes have been performed, where dialysate was present only in the second part of the procedure. In all the HD and UFD procedures LAL test assays were performed on dialysate at the same times as C3a and neutrophil determinations. Our findings seem to suggest that the dialysate can be a source of complement activating factors; complement activation detectable by C3a plasma levels can ensue when LAL test-positive material is present in the dialysate.

Haemofiltration without substitution fluid.

Haemofiltration at its best is able to give excellent clearances of solutes in a wide molecular weight range, but the need of large amounts of reliable substitution fluid makes this technique too expensive for more widespread application. In order to give an 'adequate' treatment by a safe, well tolerated, effective and comparatively cheaper method, haemofiltration without substitution fluid (HWSF) has been carried out. This method, consisting of the regeneration of appropriate amounts of pure convected plasma water by highly permeable, high surface area dialysis membranes, has been utilised for several months in four patients, with encouraging clinical results.

Hemofiltration in diabetic uremic patients.

The increasing number of Diabetic Uremic Patients (DUP) starting the substitutive treatment (ST) constitutes a difficult and often disappointing problem in terms of efforts, clinical results and side-effects. While treatment of these patients by C.A.P.D. is well documented, the adoption of Hemofiltration (HF), has been, up to now scarcely considered. In order to define the potentialities of a HF policy in the treatment of these patients, data from 6 DUP treated with postdilutional HF for a 10.6 months/patient period were collected on a multi-center basis and retrospectively examined. Good results were achieved in terms of vascular stability, control of arterial hypertension and of retinopathy, clinical complications and hospitalization rate. Although C.A.P.D. may represent a first choice treatment for DUP with residual function, satisfactory glicemic control, difficult blood access and a motivation to full autonomization, HF may constitute a logical alternative when C.A.P.D. should be unmanageable (visus impairment, history of repeated peritonitis and dismetabolism, considerable weight gain): an integration of HF and C.A.P.D. can assure PDU with a continuative treatment.