BACKGROUND: Anaemia is one of the major clinical characteristics of patients with chronic renal failure, and has a considerable effect on morbidity and mortality. Adequate dialysis is of paramount importance in correcting anaemia by removing small and medium-sized molecules, which may inhibit erythropoiesis. However, high-molecular-weight inhibitors cleared only by means of highly porous membranes have also been found in uraemic serum and it has been claimed from uncontrolled studies that high-flux dialysis could improve anaemia in haemodialysis patients. METHODS: We therefore planned this multicentre randomized controlled trial with the aim of testing whether the use of a large-pore biocompatible membrane for a fixed 12-week follow-up improves anaemia in haemodialysis patients in comparison with the use of a conventional cellulose membrane. Eighty-four (5.3%) of a total of 1576 adult haemodialysed patients attending 13 Dialysis Units fulfilled the entry criteria and were randomly assigned to the experimental treatment (42 patients) or conventional treatment (42 patients). RESULTS: Haemoglobin levels increased non-significantly from 9.5+/-0.8 to 9.8+/-1.3 g/dl (dP=0. 069) in the population as a whole, with no significant difference between the two groups (P:=0.485). Erythropoietin therapy was given to 32/39 patients (82%) in the conventional group, and 26/35 (74%) in the experimental group (P:=0.783) with subcutaneous administration to 26/32 patients in conventional and to 23/26 patients in experimental group, P:=0.495. Dialysis dose (Kt/V) remained constant in both groups (from 1.30+/-0.17 to 1.33+/-0.20 in the conventional group and from 1.28+/-0.26 to 1.26+/-0.21 in the experimental group, P:=0.242). Median pre- and post-dialysis beta(2)-microglobulin levels remained constant in the conventional group (31.9 and 34.1 mg/dl at baseline) and decreased in the experimental group (pre-dialysis values from 31.1 to 24.7 mg/dl, P:=0.004 and post-dialysis values from 24.8 to 20.8 mg/dl, P:=0.002). Median erythropoietin doses were not different at baseline (70 IU/kg/week in conventional treatment and 90 IU/kg/week in experimental treatment, P:=0.628) and remained constant during follow-up (from 70 to 69 IU/kg/week in the conventional group and from 90 to 91 IU/kg/week in the experimental group, P:=0.410). Median erythropoietin plasma levels were in the normal range and remained constant (from 12.1 to 12.9 mU/ml in the conventional group and from 13.2 to 14.0 mU/ml in the experimental group, P:=0.550). CONCLUSIONS: This study showed no difference in haemoglobin level increase between patients treated for 3 months with a high-flux biocompatible membrane in comparison with those treated with a standard membrane. When patients are highly selected, adequately dialysed, and have no iron or vitamin depletion, the effect of a high-flux membrane is much less than might be expected from the results of uncontrolled studies.

Aged↗

PubMed2000

Removal of small and middle molecules by convective techniques.

The current renewed interest in haemofiltration (HF) is due mainly to its potential advantages in reducing morbidity and mortality. We analysed the data obtained from eight patients treated with pre-dilution HF and compared them with the calculated post-dilution HF and haemodialysis (HD) data in order to quantify the depurative performance of HF and to assess whether its claimed ability to improve cardiovascular stability is at least partially related to less sodium removal. The urea clearance (as a marker of small molecules) of pre-dilution HF was equivalent to that of standard low-flux HD and approximately 20% higher than that of postdilution HF. For a calculated increase of 117% in the dialytic clearance of beta2-microglobulin using high-flux HD, the increase in beta2-microglobulin removal with HF was only 30%. The intradialytic decrease in plasma water beta2-microglobulin concentrations was 73% (vs 53% in HD) followed by a post-dialytic rebound of 85% (vs 42% in HD). The interdialytic concentrations of beta2-microglobulin were always lower. At the start of the subsequent session, the beta2-microglobulin concentrations observed in HF-treated patients were 92% of those in the patients treated with HD. Sodium removal was similar using both HF modalities at the same total dialysate and reinfusate sodium concentrations, and lower than in the case of HD. HF makes it possible to obtain constantly lower plasma water beta2-microglobulin concentrations whose long-term clinical relevance has to be verified. Under usual operational conditions, sodium removal is less with pre-dilution HF than with HD, thus raising some doubts about the intrinsic capacity of HF to improve cardiovascular stability by a mechanism other than less sodium removal.

Hemofiltration↗

PubMed2000

Cardiovascular disease in chronic renal failure: the challenge continues. Registro Lombardo Dialisi e Trapianto.

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Cardiovascular Diseases↗

PubMed2000

Treatment modalities in comparison: when do clinical differences emerge?

BACKGROUND: Despite technological advances in dialysis equipment and modalities, the survival, morbidity and quality of life of uraemic patients undergoing regular haemodialysis treatment are still severely affected by acute intradialysis and long-term complications, possibly related to the treatment itself. Convective treatment modalities, such as haemodiafiltration and haemofiltration, are thought to be further improvements over standard diffusive haemodialysis. Moreover, several of the pathways activated in patients during dialysis have the potential to produce many side-effects. These occur three times a week, and are particularly intense in patients dialysed with so-called 'bio-incompatible' membranes. Thus the biocompatibility of dialysis membranes is increasingly recognized as one of the main factors in the improvement of dialysis treatment. METHODS: The main clinical studies to date are reviewed to highlight the clinical effects of different treatment modalities and membranes on the most important acute and long-term haemodialysis-related complications. RESULTS: Epidemiological studies suggest that semisynthetic and synthetic membranes may reduce morbidity and mortality in dialysis patients. Despite the proven biological superiority of biocompatible membranes, we lack definitive evidence that thrice-weekly complement and cell activation over a period of years is detrimental to patients, because the results of prospective randomized studies are conflicting. However, it is important to remember that factors other than the dialysis membrane could influence the 'biocompatibility' of dialysis, including the dialysate, dialyser geometry, the distribution of blood in the dialyser, reuse, the sterilizant and materials used in reprocessing. CONCLUSIONS: Further large-scale prospective and randomized trials with a long follow-up are needed in order to better clarify the clinical effect of different treatment modalities on the morbidity and mortality of patients on chronic renal replacement therapy. In particular, it must be clarified whether the possible clinical differences in treatment modalities are based on differences in the clearance of middle molecules or on biocompatibility, or, more generally, on the increasingly recognized clinical importance of high-flux treatments, and the possible interaction between membrane flux and biocompatibility.

Anemia↗

PubMed2000

Umbilical cord blood transplants.

With the establishment of cord blood banks, the number of related and unrelated umbilical cord blood transplants is increasing worldwide. Close links have been established with the cord blood banks. Available data showed that umbilical cord blood transplants offer overall results comparable to those obtained with related or unrelated bone marrow transplants. Several differences were found: engraftment with cord blood was delayed, resulting in an increased incidence of early transplant complications, and the incidence of acute and chronic graft-versus-host disease was significantly reduced with cord blood grafts, even in HLA-mismatched transplants and in adults. In patients with leukemia, the rate of relapse appeared to be similar to that documented in bone marrow transplant recipients. These data confirm the potential benefit of using umbilical cord blood hematopoietic stem cells for allogeneic transplants.

Blood Banks↗

PubMed2000

Spurious estimations of sodium removal during CAPD when [Na](+) is measured by Na electrode methodology.

BACKGROUND: The aim of this study was to investigate the effect of pH and glucose concentration on sodium removal and the dialysate and plasma sodium ratio (D/PNa) as measured by means of a flame photometer (NaF) or direct ion-selective electrode (NaE) in continuous ambulatory peritoneal dialysis (CAPD). METHODS: In vitro, glucose concentration, pH, NaF, and NaE were measured in fresh peritoneal dialysis solutions (PDSs) before and after the addition of glucose or KOH. In vivo, 66 four-hour peritoneal equilibration tests were performed in 35 patients on CAPD using a low pH PDS with a glucose concentration of 3.86%. RESULTS: In vitro, NaF and NaE were significantly influenced by the glucose concentration and pH of the PDS. In vivo, in fresh PDS, there was a significant difference between the NaF and NaE results; the respective median values were 132.1 (interquartile range 129.3 to 137.5) versus 138.0 (134.4 to 141.5) mmol/L (P < 0.0001). The D/PNa ratio calculated by NaE was significantly lower than that calculated by NaF (0.88 +/- 0.03 vs. 0.91 +/- 0.04 and 0. 90 +/- 0.03 vs. 0.94 +/- 0.04 at 60 and 240 min, respectively, P < 0.0001), whereas there was no significant difference between the NaE and NaF values after correction for plasma water and a Donnan factor of 0.96 (0.88 +/- 0.03 vs. 0.88 +/- 0.04 and 0.90 +/- 0.03 vs. 0.91 +/- 0.04, P < 0.3473). Sodium removal was significantly lower when calculated as NaE than when calculated as NaF (43.9 +/- 32.7 vs. 61.0 +/- 32.2 mmol, P < 0.0001). CONCLUSIONS: The fresh PDS sodium concentration can be corrected using a glucose concentration-related factor. The D/PNa ratio calculated as NaE or NaF is not different after correction for plasma water and a Donnan factor of 0.96. Sodium removal must be measured by means of NaF rather than NaE. This could have an important clinical impact.

Adult↗

PubMed2000

Human cytomegalovirus immediate-early mRNA detection by nucleic acid sequence-based amplification as a new parameter for preemptive therapy in bone marrow transplant recipients.

Human cytomegalovirus (HCMV) infection was monitored retrospectively by qualitative determination of immediate-early (IE) mRNA by nucleic acid sequence-based amplification (NASBA) in a series of 51 bone marrow transplant (BMT) recipients. The qualitative results for IE mRNA obtained by NASBA were compared with those obtained by prospective quantitation of HCMV viremia and antigenemia and retrospective quantitation of DNA in blood (DNAemia) by PCR as well as by qualitative determination of late pp67 mRNA by NASBA. On the whole, of the 39 HCMV-positive patients (all asymptomatic), HCMV was detected in 14 (35.9%) by quantitation of viremia, 15 (38.5%) by detection of pp67 mRNA by NASBA, 32 (82.1%) by quantitation of DNAemia, and 33 (84.6%) by quantitation of antigenemia, while HCMV was detected in 38 (97.4%) patients by detection of IE mRNA by NASBA. In the immunocompetent host, IE mRNA was not detected by NASBA in 100 blood donors or during reactivated infections in 30 breast-feeding mothers. Likewise, NASBA did not detect IE mRNA in 56 solid-organ transplant recipients in the first 21 days after transplantation. By using NASBA for detection of IE mRNA as the reference standard for detection of HCMV infection in blood samples, the diagnostic sensitivities were 67.7% for quantitation of DNAemia, 59.0% for quantitation of antigenemia, 18.3% for detection of pp67 mRNA by NASBA, and 16.0% for quantitation of viremia. Specificities and negative and positive predictive values were >90.0, >70.0, and >80.0%, respectively, for all four assays. The mean times to first HCMV detection after bone marrow transplantation were 37.7 +/- 15.4 days for detection of IE mRNA by NASBA, 39.6 +/- 15.6 days for quantitation of antigenemia, 40.9 +/- 15.2 days for quantitation of DNAemia, and 43.7 +/- 16.3 or 43.7 +/- 17.5 days for quantitation of viremia and detection of pp67 mRNA by NASBA, respectively. On the whole, 31 BMT recipients received preemptive therapy by using confirmed antigenemia positivity as a cutoff, while 35 patients could have been treated by using NASBA positivity as a cutoff and 31 could have been treated by using quantitation of DNAemia as a cutoff. In single patients, IE mRNA was detected in every episode of active HCMV infection, mostly preceding and sometimes accompanying antigenemia and DNAemia, whereas pp67 mRNA was detected only concomitantly with the highest peaks of infection. HCMV IE mRNA detection may represent a useful parameter for initiation of preemptive therapy in BMT recipients.

Adolescent↗

PubMed2000

Differences in incidence of reported asthma related to age in men and women. A retrospective analysis of the data of the European Respiratory Health Survey.

Sex differences in asthma prevalence and morbidity, assessed with different methods in different populations, have raised several hypotheses about the different susceptibility to asthma in men and women. However, information on the incidence of asthma by age and sex is limited. The aim of this study was to estimate the age- and sex-specific incidence of asthma from birth to 44 yr of age in men and women across several countries, and to evaluate the main factors influencing asthma incidence in young adults. The data of the European Community Respiratory Health Survey, an international, cross-sectional, population-based survey, which were collected in 16 countries from 1991 to 1993 according to a common protocol, and which pertained to 18,659 subjects, were analyzed retrospectively, using the reported age of the first attack as the onset of asthma. During childhood, girls had a significantly lower risk of developing asthma than did boys (relative risk [RR]: 0.74 and 0.56 in the 0- to 5-yr and 5- to 10-yr age classes, respectively). Around puberty, the risk was almost equal in the two sexes (RR = 0.84; 95% confidence interval [CI]: 0.65 to 1.10 in the 10 to 15-yr age class). After puberty, the risk in women was always significantly higher than that in men (RR: 1.38 to 5.91). This pattern was consistent in all of the 16 countries studied, and was not influenced by recall or cohort effects. When the effects of airway caliber and smoking were studied with a case-control design, the results showed that women's greater susceptibility to asthma in early adulthood was at least partly, explained by their smaller airway caliber (the OR decreased from 2. 04 [95% CI: 1.32 to 3.15] to 1.47 [95% CI: 0.89 to 2.44] after controlling for height-adjusted FEV(1)); while smoking did not increase the risk. This analysis strongly confirms that the incidence of asthma shows a sex reversal during puberty, and suggests that airway caliber, in addition to hormonal factors, could play an important role in explaining the different patterns of asthma incidence in men and women.

Adolescent↗

PubMed2000

Alternative therapies and the Di Bella affair in pediatrics. A questionnaire submitted to Italian pediatric oncologists and hematologists.

BACKGROUND AND OBJECTIVE: Over the last 2-3 years in particular, the so-called Di Bella therapy (DBT) become the most famous of alternative treatments applied to pediatric oncology and hematology in Italy. Many Italian oncologists and hematologists had to cope with the problems that it introduced and the treatment also elicited heated reactions all over Europe. We attempted to evaluate the impact of this treatment on children with cancer. DESIGN AND METHODS: A questionnaire prepared with the aim of addressing the use of alternative therapies in pediatric hematology and oncology was circulated to the 48 centers (or divisions) belonging to AIEOP (Associazione Italiana di Oncoematologia Pediatrica) [Italian Pediatric Oncology and Hematology Association] and FONOP (Forza Operativa Nazionale di Oncologia Pediatrica) [National Pediatric Oncology Task Force]. The questionnaire consisted of 9 questions elaborated to give credit to the case-related and professional experiences of the colleagues we contacted. RESULTS: Forty-three centers replied to the questionnaire. Request to switch to DBT represented a considerable problem, involving the vast majority of centers participating into this study; however, case quantification varied greatly from center to center. One of the most significant aspects is that children switched to DBT, abandoning conventional therapies, were often relapsing or had had multiple relapses (from solid tumor or leukemia), but some children abandoned conventional therapies at an early stage and/or without fully exploiting the curative potential of these therapies. INTERPRETATION AND CONCLUSIONS: This study allowed us to obtain an evaluation of the impact of DBT in children with oncologic or hematologic disorders. It also highlights the importance of cultivating physician-parent dialogue and provides an opportunity for a few pedagogic thoughts on the attitude and opinions of pediatricians on this problem.

Child↗

PubMed2000

The role of underlying nephropathy in the progression of renal disease.

BACKGROUND: Disease-specific pathogenic mechanisms may be major determinants of the spontaneous rate of progression of chronic renal failure (CRF). To clarify the role of different underlying renal diseases, we examined the rate of CRF progression in 886 patients with chronic nephropathies. METHODS: Secondary analysis of two multicenter, prospective randomized trials: the Northern Italian Cooperative study (NIC) and the AIPRI study (ACE-Inhibition in Progressive Renal Insufficiency). Univariate and multivariate analyses of variance were used to select the covariates possibly related to CRF progression (estimated by means of the slope of the reciprocal of SCr against time), focusing on the contributory role of primary renal diseases. RESULTS: The overall rate of CRF progression was relatively low but there was a considerable difference in the slopes relating to the underlying nephropathy (particularly evident in the patients with chronic glomerulonephritis (CGN)). The median rate of CRF progression in both studies was more rapid in patients with polycystic kidney disease (PKD) and CGN than in those with other nephropathies. Multivariate analysis showed PKD as an independent predictor of the CRF progression rate only in the NIC Study (P < 0.0015); the selected variables in both studies predicted a variation of only 15-18% in the CRF progression rate. CONCLUSION: The underlying renal disease certainly plays a role in the natural history of CRF, but the variability of the CRF progression rates related to different renal diseases and between individuals with the same diagnosis underlines the need for caution in evaluating risk factors and predicting single patient outcomes.

Adult↗

PubMed2000

Hematopoietic stem cell transplantation in childhood: report from the bone marrow transplantation group of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

BACKGROUND AND OBJECTIVE: Transplantation of hematopoietic stem cells from different sources is being increasingly used to treat a variety of diseases in children. Transplant procedures and indications have changed considerably during recent years. Monitoring of information about these changes is useful for interpretation of nationwide collected data. DESIGN AND METHODS: Since 1985, Centers belonging to the AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica), performing hematopoietic stem cell transplants (HSCT) in children, and members of the AIEOP-Bone Marrow Transplant (BMT) Group annually report data on their transplant activity to the AIEOP-BMT Registry employing specially prepared patient-oriented forms. RESULTS: From January 1985 to December 1998, a total of 2,474 bone marrow (BM), peripheral blood (PB) or umbilical cord blood (CB) transplants were reported: 1,296 (52%) were allogeneic (Allo) and 1,178 (48%) autologous (Auto) transplants. These transplants were performed in 19 Italian Centers on 2,249 patients aged less than 17 years. Among Allo-transplants, 1,198 (92%) were performed using BM progenitor cells, whereas 49 (4%) CB, 42 (3%) were PB, 4 BM plus PB, and 3 BM plus CB allografts; they were performed using HLA-identical sibling donors in 867 cases (67%) and alternative donors (i.e. partially-matched relatives or unrelated donors) in the remaining 429 (33%) cases. Allogeneic transplants were performed on 786 (67%) patients with malignancy and on 395 (33%) patients with non-malignant disorders. In the last 6 years, the number of Allo-transplants per year exceeded that of Auto-transplants. Of the Auto-transplants, 775 (66%) were performed using BM, and 403 (34%) using PB alone or combined with BM hematopoietic stem cells. Indications for Auto-BMT were myelo-lymphoproliferative disorders in 524 (49%) cases, solid tumor in 533 (50%) cases and non-malignant disease in 11 (1%) cases. In the last 5 years, the use of PB for autografts has increased from 7% to 70%. INTERPRETATION AND CONCLUSIONS: These data reflect the development and present status of HSCT in Italy and provide a basis for patient counseling and health care planning.

Adolescent↗

PubMed2000

Membrane compatibility, flux and HCV infection in dialysis patients: newer evidence.

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Biocompatible Materials↗

PubMed2000

Vancomycin-resistant Enterococcus faecium infection in three children given allogeneic hematopoietic stem cell transplantation: clinical and microbiologic features.

BACKGROUND AND OBJECTIVES: The emergence of vancomycin-resistant enterococci (VRE) as nosocomial pathogens is a major problem in the US; in Europe, VRE nosocomial infections are uncommon and only rarely have been reported in Pediatric or Neonatal Units. The aim of this study is to report on the clinical and microbiological features of VRE infections in 3 children given hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: Five episodes of vancomycin-resistant Enterococcus faecium (VREF) infection were diagnosed in 3 children given an allogeneic HSCT. Molecular methods, such as random amplification of polymorphic DNA (RAPD) fingerprinting and automated ribotyping, were used in order to define the circulation of strains. RESULTS: All the isolates were resistant to all commercially available agents and showed the VanA genotypic profile. All children were successfully treated with the combination of quinupristin/dalfopristin (QD) plus teicoplanin (TEC), although treatment was not sufficient to eradicate the micro-organism promptly from the gastrointestinal tract. All our children are still alive. After the first isolation of VRE, a surveillance protocol was started and we documented that the rate of colonization in children and their mothers was less than 1.5%. The RAPD method demonstrated the possible nosocomial transmission of one strain. INTERPRETATION AND CONCLUSIONS: Our experience demonstrates that VRE infection is a life-threatening complication in children given HSCT. Prompt diagnosis of this infection and its treatment with the combination of QD and TEC can successfully manage this severe infection in profoundly immunocompromised patients.

Anti-Bacterial Agents↗

PubMed2000

Liver disease in dialysis patients.

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Female↗