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Biomedical subjects

R Coppo

Publications and source records attributed to R Coppo.

At least 145 records · Page 8Linked to original sources
PubMedDate not supplied

Use of alkaline rinsing solution to prevent hypersensitivity reactions during hemodialysis: data from a multicentre retrospective analysis.

BACKGROUND: Hypersensitivity reactions (HSRs) can be enhanced by contact phase system activation leading to bradykinin (BK) generation. In patients treated with angiotensin converting enzyme inhibitors (ACE-I), an impaired kinin degradation can magnify the phenomenon. We have previously demonstrated that the electronegative charge of the dialysis membrane (e.g. AN69) and other cofactors including diluted blood buffer power promote BK generation, and that kallikrein synthesis on diluted plasma may be inhibited by keeping the pH value above 7.4. Our in vitro and ex vivo studies have demonstrated that the use of an alkaline solution to rinse both filter fluid compartments before their clinical use can inhibit the activation of mediators that are likely to be involved in HSRs. METHODS: The present study was aimed at gathering data from a multicenter retrospective analysis of HSRs in 15 Italian centers, with special attention to the precautions chosen to avoid recurrence, and at evaluating whether a rinsing procedure maintaining the pH of the diluted blood above 7.4 may prevent further HSRs. RESULTS: HSRs were reported in 54 patients on dialysis treatment between January 1995 and June 1997. 39/54 HSRs occurred when AN69 was used. In 44.4% of cases, HSRs were associated with ACE-I treatments. The HSR prevention modalities varied considerably among the centers. Two thirds of the nephrologists did not change their dialysis prescription but tried to modify the acidic environment of the patient's diluted blood at the first contact with the dialysis device using an alkaline rinsing procedure (BioPrime with alkaline solution). In other cases ACE-I withdrawal or a change of dialysis membrane was adopted. Thirty-six patients who received alkaline rinsing of the filters were monitored for a total of 686 months (median 17.6 months/patient) to control HSR recurrences. None of the patients enrolled in this study developed new episodes of HSRs. CONCLUSIONS: Even if considered with the caution called for by this kind of study, which was retrospective and uncontrolled, our data suggest a protective effect of the alkaline rinsing procedure with buffered solutions in the development of HSRs.

Anaphylaxis↗
PubMedDate not supplied

Treatment of IgA nephropathy with angiotensin converting enzyme inhibitors: design of a prospective randomized multicenter trial.

Although several in vitro studies and clinical observations suggest that ACE-inhibitors (ACE-I) are a promising treatment for IgA nephropathy (IgAN), meta-analysis of published data is not yet conclusive. Therefore, a European double-blinded, prospective, randomized therapeutic trial was designed to evaluate ACE-I treatment benefits in young IgAN patients (<35 years old) with persistent moderate proteinuria (>1<3.5 g/day/1.73 m2) and fair renal function (creatinine clearance >50 mL/min/1.73 m2). Patients enrolled are randomly assigned to benazepril (0.2 mg/kg/day) or placebo. Patients should be enrolled within a five year recruitment period (end on December 2003) for a total duration of follow-up of six years (end on December 2004). Hypertension and some genetic, histological and immunological factors will be evaluated to clarify their eventual role in the final response to ACE-I treatment.

Adolescent↗
PubMedDate not supplied

[Glomerulonephritis and renal sclerosis: new therapeutic proposals (review)].

The treatment of immuno-mediated glomerulonephritides is presently based upon a limited series of drugs. Albeit evidence-based medicine relies solely upon controlled trials, there is a need to follow new perspectives with an open mind, since they may lead to tomorrow's therapy. Several original and innovative approaches to treat inflammatory glomerular diseases have been recently reported, including drugs designed to limit the effect of pro-inflammatory and pro-sclerotic cytokines (recombinant monoclonal antibodies, receptor antagonists, gene therapy providing viral transfection of genes, antisense oligonucleotides, aptamers, inhibition of transcription factors, active immunization). Moreover, newer options are being proposed, as in the case of enhancing natural anti-inflammatory cytokines or intracellular signalling limiting inflammation. Some of these proposals, which are briefly reviewed in this article, are likely to enter soon clinical investigation and to become in the next future standard treatment for glomerular diseases.

Fibrosis↗
PubMedDate not supplied

[A severe case of nephrotic syndrome].

A 14-year-old girl presented at the Renal Unit with clinical and laboratory pictures of a severe nephrotic syndrome. It was done a kidney biopsy which detected a picture of "minimal change". As the patient had no benefit from the prednisone therapy, she underwent to another biopsy which detected, this time, a Focal Glomerulosclerosis. Despite the immunosuppressive therapy, the renal function deteriorated and, therefore, the patient began dialysis. After a while, the girl received a cadaveric kidney transplantation but the nephrotic syndrome recurred again and the patient went back to chronic dialysis.

Adolescent↗
PubMedDate not supplied

[Biocompatibility of the acetate in the dialysis fluid].

PURPOSE: Dialytic vasculopathy is a major morbidity and mortality risk factor in patients undergoing chronic dialysis treatment. Among the pathogenetic factors some are related to the uremic condition, others are due to biocompatible reactions to dialytic materials. Endothelial cells (EC) are the target of the mediators released during bioincompatible reactions, and the related effects could be considered the initial event eliciting the vasculopathy pathogenesis. Among the others, we focused our attention on the role played in this process by the inducible isoform of nitric oxide (NO) synthase (iNOS). In previous studies we demonstrated that bioincompatible membranes, as well as acetate-containing dialysis buffers stimulate iNOS gene expression and activity in endothelial cells in culture. In this study, we planned to evaluate the potential role of a new dialysis buffer in which acetate has been substituted with HCl as a stabilizer. METHODS: ECs were incubated for 12 h at 37 degrees C with different dialysis buffers: acetate (Acet), standard bicarbonate (Bic), acetate-free buffer (AF) and HCl-bicarbonate (BicHCl). We evaluated in reverse transcriptase polymerase chain reaction (RT-PCR) the gene transcription for iNOS, the NOS activity (as the production of H3 citrulline from H3 arginine by ionic exchange chromatography), EC proliferative (H3 thymidine incorporation) and pro-apoptotic rate (TUNEL analysis) and the nuclear translocation of the transcriptional factor NF-kappaB (EMSA). RESULTS: Acetate, even in the low concentration present in Bic was able to induce a significant iNOS gene transcription (results expressed as relative units and referred to basal values: Acet 1.9 +/- 0.01 fold increase, p<0.01; Bic 1.45 +/- 0.03 p<0.05; BicHCl 1.24 +/- 0.01; AF 1.17 +/- 0.02) and translation. Acetate at concentrations both of 3 mmoL and 38 mmoL (present in the bicarbonate buffer) significantly increased the enzymatic NOS activity vs unconditioned ECs: Acet 3.46 +/- 0.3, p<0.0005; Bic 1.69 +/- 0.2, p<0.005; BicHCl 1.24 +/- 0.15; AF 1.17 +/- 0.05. The EC proliferative index was significantly depressed by acetate containing dialysis buffers (unconditioned ECs 100%, Acet 38 +/- 15%, p<0.01; Bic 65 +/- 6%, p<0.05; AF 87 +/- 8%; BicHCl 75 +/- 6%). The percentage of apoptotic ECs was significantly increased by buffers contain-ing Acet vs BicHCl and AF. Finally, acetate at the concentrations present in Acet and Bic activated and promoted the nuclear translocation of the transcriptional factor NF-kappaB in ECs (p<0.01 vs unconditioned cells). CONCLUSIONS: The acetate-free dialysis buffers have better biocompatibility and potentially down-modulate the flogistic and sclerotic processes responsible for dialytic vasculopathy.

Acetates↗
PubMedDate not supplied

[Kidney transplantation in children].

Indications, procedures, complications, pharmacokinetics and outcomes of renal transplantation are different in children and in adults. Subjects <18 yrs old, are often included in a unique list as in Italy, benefiting from donors <15 yrs old, and the waiting time is reduced to <12 months in 71% of cases. The risk of thrombosis limits the use of donors <2 yrs and trans-plantation in infants <1 yr. The age at kidney transplantation is <5 yrs in 20-30% of children. In Italy living-related trans-plantation (LRT) is performed in 7% of cases, while in the USA it is more common (57%) and is often pre-emptive before entering dialysis (24%). Current therapy tends to reduce steroid treatment doses and, optimizing induction therapy with IL-2R inhibitors, using tacrolimus or mycophenolate or sirolimus. Transplanted patient survival is better in children than in adults (94-98% at 5 yrs). Infections, cardiovascular diseases and neoplasia induce 34, 15 and 12% of deaths, respectively, at 10 yrs; morbidity for infections and lymphoproliferative disease is increasing. Acute rejections declined from 70% in 1987 to 31% in 2002 in cadaveric transplantation (CT) and renal survival at 3 yrs increased from 50% in 1985 to 82% for CT and up to 92% in LRT. In adolescents (11-17 yrs old) renal survival is lower than in infants and in adults <65 yrs old. Renal losses are due to chronic transplant nephropathy (32%), vascular thrombosis (13%) and the recurrence of the original nephropathy (focal glomerulosclerosis up to 50%, membrano-proliferative glomerulonephritis up to 30%, and primary hyperoxaluria up to 90% if combined kidney-liver transplantation is not performed). Growth improves after transplantation particularly in children <5 yrs, while it is not completely satisfactory in adolescents. Overall, results indicate that kidney transplantation in children has very much improved and will offer in the near future even more favorable outcomes.

Child↗
PubMedDate not supplied

[Role of food antigens and alcohol in idiopathic nephritis with IgA deposits].

It is generally thought that antigens inducing the formation of IgA immune complexes in primary IgA nephropathy and responsible for mesangial immune deposits are of infectious and alimentary origin. To investigate the possible role of alimentary antigens in eliciting the IgA mucosal immune response we studied the reactivity and the formation of mesangial IgA deposits in rodents following different experimental conditions: a) on gluten-free diet and oral immunization with gliadin; b) on gluten and soya free diet and oral immunization with soya; c) on chronic alcoholic intoxication. We found that oral immunization with gliadin induced the formation of mesangial deposits of IgA similar to those observed in human primary IgA nephropathy. On the contrary, oral immunization with soya failed to induce the formation of similar immune deposits even though the lectin components in soya and in gliadin are similar. Chronic ethanol intoxication induced an increase in serum IgA against alimentary antigens suggesting an increase in intestinal permeability due to alcohol. Mean times we observed significant IgA mesangial deposits. Our experimental data suggest that alimentary antigens can play a significant role in inducing primary IgA nephropathy.

Alcoholism↗
PubMedDate not supplied

Primary biliary cirrhosis and rheumatic diseases: a clinical, immunological and immunogenetical study.

Clinical investigation of Primary Biliary Cirrhosis (PBC) patients showed an elevated frequency of rheumatic disorders, as well as their frequent appearance in asymptomatic PBC. Anticentromere region antibodies in PBC patients were pathognomonic for concomitant complete or incomplete CREST syndrome. These antibodies were only found on the HEp2 cell substrate. The constant finding of immune-complexes (IC) with IgM antibody component suggests that they play a role in the pathogenesis of PBC. No statistically significant correlation was found between the amount and classes of circulating IC, HLA class I antigens and rheumatic disorders during PBC.

Adult↗