Hemodiafiltration with endogenous reinfusion with and without acetate-free dialysis solutions: effect on ESA requirement.

BACKGROUND: Hemofiltrate reinfusion (HFR) is a form of hemodiafiltration (HDF) in which replacement fluid is constituted by ultrafiltrate from the patient 'regenerated' through a cartridge containing hydrophobic styrene resin. Bicarbonate-based dialysis solutions (DS) used in routine hemodialysis and HDF contain small quantities of acetate (3-5 mM) as a stabilizing agent, one of the major causes of intradialytic hypotension. Acetate-free (AF) DS have recently been made available, substituting acetate with hydrochloric acid. The impact of AF DS during HFR on Hb levels and erythropoietic-stimulating agent (ESA) requirement in chronic dialysis patients was assessed. PATIENTS AND METHODS: After obtaining informed consent, 30 uremic patients treated by standard bicarbonate dialysis (BHD, DS with acetate) were randomized to treatment in 3-month cycles: first AF HFR, followed by HFR with acetate, and again AF HFR. At the beginning and end of each period, Hb and ESA requirements were evaluated. RESULTS: A significant increase in the Hb level was observed throughout all periods of HFR versus BHD (from 11.1 to 11.86 g/dl; p = 0.04), with a significant decrease of ESA requirements from 29,500 to 25,033 IU/month (p = 0.04). CONCLUSION: Regardless of the presence or absence of acetate in DS, HFR per se allows a significant lowering of ESA dosage versus BHD, while at the same time increasing Hb levels. Taking for granted the clinical impact produced, HFR seems to provide a relevant decrease in end-stage renal disease patient costs.

Effect of on-line hemodiafiltration with endogenous reinfusion (HFR) on the calcium-phosphorus metabolism: medium-term effects.

AIM: The purpose of the study was to examine the effect of hemodiafiltration with endogenous reinfusion (HFR) compared to hemodialysis (HD) on 28 uremic patients with secondary hyperparathyroidism (2HPT) but positively selected for good and stable control of phosphatemia in order to evaluate the independent effects of dialysis treatments on bone turnover metabolism. METHODS: The study was divided into 3 periods of observation: a) HD for three months; b) HFR for three months; c) HFR for a further 3 months. We analysed the trend of: whole PTH, 1-84 PTH, 7-84 PTH, alkaline phosphatase and its bone isoenzyme, total and ionised calcium, phosphatemia, dose of phosphate binder agents, beta2-microglobulin, CRP. All the variations found were evaluated through mean values +/- SD, t-tests, multivariate analysis. RESULTS: We observed a deceleration in bone turnover characterized by a reduction of the total and bone alkaline phosphatase (IU/mL) from 92.3 +/- 82.8 and 35.8 +/- 49.8 at the end of HD to 63.4 +/- 23.9 and 16.0 +/- 8.7 at the end of HFR, respectively, and 1-84 PTH from 317.5 +/- 264.6 pg/mL at the end of HD to 287.5 +/- 258.9 pg/mL at the end of the 3rd month of HFR. Beta2-microglobulin was reduced from 32.9 +/- 16.1 mg/L at the end of HD to 26.4 +/- 8.1 mg/L already at the end of the first three months of HFR. CRP was reduced from 2.5 +/- 2.6 mg/dL at the beginning of the study to 1.3 +/- 1.7 mg/dL at the end of HFR. There were no differences with regard to: dialytic efficiency, nutritional status, calcemia, phosphatemia (maintained in the K-DOQI range for the entire duration of the study), also thanks to more careful use of phosphate chelating agents. CONCLUSION: We are of the opinion that HFR - essentially thanks to the use of ultrapure endogenous infusate - induces a deceleration in bone turnover due to 2PHT. In addition, phosphate subtraction in HFR is better compared to HD, thanks to the improvement of the anti-inflammatory conditions by removing the cytokines harmful to bone metabolism and excluding a priori the negative effects related to hyperphosphatemia.

[Update of the Italian Society of Nephrology Project No. 1 of the 2004-2006 SIN programme]. / Update sul progetto SIN n. 1 del programma SIN 2004-2006: qualità e accreditamento delle strutture di nefrologia, dialisi e trapianto.

In the last few years the Italian Society of Nephrology has addressed many technical-scientific and management aspects to better patient satisfaction. Project No. 1 of the 2004-2006 programme on 'Quality and Accreditation of National Renal Units' focuses on four essential points. The first is the questionnaire mailed to all the Presidents and Regional Delegates on the relationship between Nephrology units, Local Government Health-System and the Regional Healthcare Agency. The results evidence that the 'political' decision-making power of nephrologists decreases in the absence of a national strategy. The second point, in collaboration with the National Census Group, includes the quality analysis and the standardization of resources (human and structural) and management of the Renal Units. The third point is based on 'Educational Courses for Quality and Accreditation' held in Rome (3-5 October 2005: L'Accreditamento all'Eccellenza dell'Unita' Operativa di Nefrologia, Dialisi e Trapianto; 17-19 October 2005: Il Manuale di Accreditamento della Specialità di Nefrologia). The courses aim at training members responsible for each region to hold courses in their specific region to create a network including each single Renal Unit to create an acceptable homogenous language on the models of analysis and on the correct use of 'The Guide for Excellence Accreditation'. The fourth point concerns both the on-line Guide for Excellence Accreditation and 'Peer Review Accreditation' and the NEQUASY (Nephrology Quality System) project. The manual must be 'user friendly' allowing each Centre to self-evaluate using national and regional standards.

Effect of priming with diphtheria and tetanus toxoids combined with whole-cell pertussis vaccine or with acellular pertussis vaccine on the safety and immunogenicity of a booster dose of an acellular pertussis vaccine containing a genetically inactivated pertussis toxin in fifteen- to twenty-one-month-old children. Italian Multicenter Group for the Study of Recombinant Acellular Pertussis Vaccine.

OBJECTIVE: To evaluate the safety and the immunogenicity of a booster dose of recombinant acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP, Biocine SpA) in 15- to 21-month-old children primed in infancy with either whole-cell diphtheria-tetanus-pertussis (DTwP) vaccine or DTaP vaccine. DESIGN: Open-label second phase of a double-masked, controlled trail, with masked analysis of serum samples. PARTICIPANTS AND SETTING: Three hundred fifty children, 15 to 21 months of age, who had been primed at 2, 4, and 6 months of age with either three doses of DTaP vaccine (n = 173) or DTwP vaccine (n = 177). The children were enrolled in eight vaccination centers in Italy. INTERVENTIONS: All children received a booster dose of the DTaP vaccine and were examined for safety at 48 hours and at 7 days after vaccination. Serum samples for evaluation of immunogenicity were obtained from 196 (55%) of the 350 children. MAIN OUTCOME MEASURES: IgG antibodies to pertussis toxin (Ptox), filamentous hemagglutinin, 69-kilodalton protein, and tetanus toxoid were measured by enzyme-linked immunosorbent assay. Pertussis toxin-neutralizing antibodies were measured by the Chinese hamster ovary cell toxin neutralization assay. MAIN RESULTS: Adverse reactions to DTaP were infrequent, and there was no difference in the incidence of local or systemic reactions in children given DTaP as a fourth dose in comparison with a first dose. One month after the DTaP booster vaccination, both groups had 6- to 40-fold increases in serum antibody concentrations to all antigens tested; the concentrations against the three pertussis antigens were higher in the DTaP-primed children (p < 0.05). The antibody titers to diphtheria and tetanus toxoids were higher in the DTwP-primed group (p < 0.05), but both groups had protective titers. The geometric mean ratio of anti-Ptox neutralizing antibody per unit of IgG anti-Ptox antibody was higher in the DTaP-primed group (p < 0.001). CONCLUSIONS: There are quantitative and qualitative differences in booster responses to DTaP vaccine in young children, depending on whether they were given DTaP or DTwP as primary immunization. This DTaP vaccine is safe and highly immunogenic as a booster.

Comparative study of a whole-cell pertussis vaccine and a recombinant acellular pertussis vaccine. The Italian Multicenter Group for the Study of Recombinant Acellular Pertussis Vaccine.

The safety and immunogenicity of an acellular pertussis vaccine containing the genetically detoxified pertussis toxin PT-9K/129G, filamentous hemagglutinin, and pertactin, together with diphtheria and tetanus toxoids, were compared with those of a whole-cell pertussis component-diphtheria-tetanus vaccine. Four hundred eighty infants were enrolled into this prospective, multicenter, double-blind study. Each infant was randomly given three doses of one of the two vaccines at 2, 4, and 6 months of age. Both local and systemic adverse reactions, reported within 48 hours and 7 days of each injection, were less frequent after the acellular vaccine than after the whole-cell vaccine. The enzyme-linked immunosorbent assay titers to pertussis toxin, filamentous hemagglutinin, and pertactin, as well as the pertussis toxin-neutralizing titer measured by the Chinese hamster ovary cell assay, were significantly higher after the acellular vaccine was given. Both vaccines induced adequate levels of anti-diphtheria and anti-tetanus antibodies. We conclude that the recombinant acellular pertussis vaccine produces fewer reactions than the whole-cell vaccine and provides a high antibody response against the antigens of Bordetella pertussis involved in bacterial adhesion and systemic toxic effects.

Importance of liver interstitial pressure on sodium retention.

Experiments were performed on 23 dogs to assess the effect of splanchnic pooling on renal hemodynamics and Na retention. When the thoracic duct pressure was raised to 40 cm H2O (HTDP), liver interstitial pressure rose from 9.0 +/- 0.4 to 19.8 +/- 1.1 cm H2O. Simultaneously, glomerular filtration rate (GFR) and renal plasma flow fell in the left kidney from 16.3 +/- 1.7 to 9.6 +/- 1.3 and from 73.7 +/- 12.2 to 44.3 +/- 9.8 ml.min-1, respectively (p less than 0.01). UNa.V fell to 59 +/- 9% of control value (p less than 0.01). Plasma antidiuretic hormone (ADH) rose from 29.5 +/- 7.7 to 46.9 +/- 9.2 pg.ml-1 (p less than 0.05). When a portocaval shunt (PCS) was opened in 10 dogs during HTDP after the first set of experimental measurements, splanchnic pressure fell from 17.2 +/- 1.1 to 11.5 +/- 1.2 cm H2O, attended by a return towards control of GFR. ADH fell significantly to 16.5 +/- 8.1 during PCS, and to 9.7 +/- 1.5 pg.ml-1 during a last, postexperimental control period. Instead, UNa.V remained unchanged at the low levels measured during HTDP alone. When the HTDP was released in the 17 dogs without, and the 10 dogs with PCS, all variables became indistinguishable from control, except for UNa.V, which remained reduced, even in 4 aldosterone-escaped animals. No significant change in any of these variables occurred in 6 sham-operated control animals. These data demonstrate that it is possible to increase interstitial liver pressure through the lymph duct.(ABSTRACT TRUNCATED AT 250 WORDS)

Demonstration of action of muzolimine on the serosal side of Henle's loop cells.

Muzolimine, a new diuretic, is known to act by inhibiting Na transport along the ascending limb of Henle's loop. Because of its ineffectiveness when perfused into the lumen, and as a result of experiments on frog skin, it is believed that muzolimine acts from the serosal cell side, unlike all other diuretics. We decided to assess the site of action of muzolimine (mucosa versus serosa) by experiments on rats. The animals were anesthetized, both ureters cannulated, and a hydronephrosis established in the left kidney by applying a counterpressure to the ureter, slowly and progressively increased up to 60 cm H2O in 3 minutes and kept stable for 20 minutes. Then either muzolimine 1.2 mg, or furosemide 4 mg, was injected i.v. together with 131I-Hypaque as a glomerular marker. Three minutes later the hydronephrosis was released in the left kidney by cutting the catheter, and urine collections were started simultaneously in both kidneys into 25 microliter glass capillaries, that were filled in continuous sequence and numbered progressively. In each urine sample from each glass capillary Na and 131I-Hypaque were measured. In 5 animals receiving furosemide, UNa rose in the left post-obstructed kidney and reached a plateau level by the 3rd to 5th sample. The rise in Na concentration, indicating delivery of urine whose Na reabsorption had been inhibited along the loop of Henle paralleled that in 131I-Hypaque, indicating that the diuretic and the glomerular marker had reached Henle's loop simultaneously, following filtration after the hydronephrosis had been discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)