Publications (53)167.48 Total impact
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Article: Different regulatory and cytotoxic CD4(+) T lymphocyte profiles in renal transplants with antibody-mediated chronic rejection or long-term good graft function.
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ABSTRACT: Comparative analysis of the different subsets of CD4(+) T-lymphocytes may provide hints on the immunologic mechanisms operating in the long-term fate of a kidney transplant. We analyzed peripheral regulatory CD4(+) T cells (Tregs) and CD4(+) cytotoxic T lymphocytes (CTLs) in antibody-mediated chronic rejection (AMCR), in middle-term kidney transplants (2-4years, MTKT) with good graft function and rejection-free history, in long-term kidney transplants (>15years, LTKT) and in normal healthy subjects (NHS). Transplant groups with good prognosis (MTKT and LTKT) displayed a significant lower amount of CD4(+)CD25(high) T lymphocytes than NHS, with a trend of a higher percentage in AMCR than in MTKT and LTKT. However, CD4(+)CD25(high) Foxp3(+) cells were significantly higher in LTKT and MTKT than AMCR. Characterization of CD4(+)CD25(high) T cells showed a marked increase of intracellular CTLA-4 in the AMCR group in respect to the other transplant groups, while the expression of the surface molecule seemed to follow a reverse trend. In addition, CD27, a costimulatory receptor involved in long-term T cell survival and prevention of immune tolerance, is significantly reduced in CD4(+)CD25(high) and CD4(+)Foxp3(+) T cells in the LTKT in respect to the other transplant groups. CD4(+)CD25(high)CD45RO(+) and CD4(+)Foxp3(+)CD45RO(+) regulatory T cells with memory function were increased in LTKT compared to NHS and for the latter also in AMCR group. Finally, CD4(+)CTLs that were quantified on the basis of granzyme A expression, were more represented in AMCR patients in comparison to the other groups. Strikingly, CD27 in the CD4(+)CTLs was suppressed in LTKT and MTKT and markedly expressed in AMCR group. No significant differences in the expression of CD28 were observed among different groups. In conclusion, different profiles of Tregs and CD4(+)CTL populations correlate with different long- term conditions of kidney-transplanted patients, suggesting their role in the development of immunologic events in kidney transplantation.Transplant Immunology 11/2012; · 1.46 Impact Factor -
Article: Microvesicles derived from endothelial progenitor cells enhance neoangiogenesis of human pancreatic islets.
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ABSTRACT: The efficacy of islet transplantation is limited by poor graft vascularization. We herein demonstrated that microvesicles (MVs) released from endothelial progenitor cells (EPCs) enhanced human islet vascularization. After incorporation into islet endothelium and beta-cells, EPC-derived MVs favored insulin secretion, survival and revascularization of islets transplanted in SCID mice. MVs induced in vitro islet endothelial cell proliferation, migration, resistance to apoptosis and organization in vessel-like structures. Moreover, MVs partially overcame the anti-angiogenic effect of rapamycin and inhibited endothelial-leukocyte interaction via L-selectin and CD40. MVs were previously shown to contain defined patterns of mRNAs. Here we demonstrated that MVs carried the pro-angiogenic miR-126 and miR-296 microRNAs (miRNAs). MVs pre-treated with RNase or derived from Dicer knocked-down EPCs showed a reduced angiogenic effect. In addition, MVs overcame the anti-angiogenic effect of the specific antagomiRs of miR-126 and miR-296, suggesting a relevant contribution of miRNAs delivered by MVs to islet endothelium. Microarray analysis of MV-stimulated islet endothelium indicated the up-regulation of mRNAs coding for factors involved in endothelial proliferation, differentiation and angiogenesis. In addition, MVs induced the activation of the PI3K-Akt and eNOS signaling pathways in islet endothelium. These results suggest that MVs activate an angiogenic program in islet endothelium that may sustain revascularization and beta-cell function.Cell Transplantation 03/2012; · 5.13 Impact Factor -
Article: A case of recurrent proliferative glomerulonephritis with monoclonal IgG deposits after kidney transplant treated with plasmapheresis.
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ABSTRACT: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a rare and recently identified disease with a poor prognosis irrespective of the treatment. Recently, the possibility of recurrent or de novo PGNMID after kidney transplantation has been reported, which is associated with a better prognosis compared to PGNMID on native kidneys. Nevertheless, at present, due to the very few cases of recurrent PGNMID diagnosed, there is no proven effective treatment. Here, we report a case of recurrent PGNMID successfully treated with plasmapheresis, steroids and mycophenolate mofetil. Our report suggests that plasmapheresis might be a valid therapeutic option to treat recurrent PGNMID.Case reports in nephrology and urology. 01/2012; 2(1):46-52. -
Chapter: The Evolution of Biocompatibility: From Microinflammation to Microvesiscles
11/2011; , ISBN: 978-953-307-377-4 -
Article: Skin cancers and other cutaneous diseases in renal transplant recipients: a single Italian center observational study.
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ABSTRACT: Kidney transplant recipients frequently suffer from skin infections and malignancies, due to the effects of long-term immunosuppressive therapy. Herein, a dermatological screening was performed to evaluate the relationship between risk factors, cutaneous tumours and other skin diseases in a group of 282 kidney transplant patients. Infectious diseases (16.7%) were the most frequent dermatological disorders, whereas cutaneous inflammatory and autoimmune diseases were relatively rare, probably due to an indirect therapeutic role of immunosuppressive regimens. Thirty patients experienced cutaneous side effects from immunosuppressants, mainly when receiving corticosteroids (p = 0.0372). We identified 99 patients (35.1%) who developed cutaneous tumours after transplantation. Cumulative tumour incidence was observed during long-term immunosuppressive therapy; no relationships were identified between skin cancer risk and single class of drug or combination regimens. When we evaluated the eventual relevance of other risk factors for skin cancers, we demonstrated a statistical significance in univariate analysis for male gender, more advanced age at transplantation, long duration of immunosuppressive regimens, no sunscreen usage, outdoor job, absence of cherry angiomas and presence of actinic keratoses (AKs). Age at transplantation (p = 0.0174), presence of AKs (p = 0.0005) and duration of immunosuppression (p = 0.0011) also confirmed their significance in multivariate analysis.European journal of dermatology: EJD 02/2011; 21(2):242-7. · 2.53 Impact Factor -
Article: Protective effect of resin adsorption on septic plasma-induced tubular injury.
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ABSTRACT: A pro-apoptotic effect of circulating mediators on renal tubular epithelial cells has been involved in the pathogenesis of sepsis-associated acute kidney injury (AKI). Adsorption techniques have been showed to efficiently remove inflammatory cytokines from plasma. The aim of this study was to evaluate the efficiency of the hydrophobic resin Amberchrom CG161 M to adsorb from septic plasma soluble mediators involved in tubular injury. We enrolled in the study 10 critically ill patients with sepsis-associated AKI and we evaluated the effects of their plasma on granulocyte adhesion, apoptosis and functional alterations of cultured human kidney tubular epithelial cells. We established an in vitro model of plasma adsorption and we studied the protective effect of unselective removal of soluble mediators by the Amberchrom CG161 M resin on septic plasma-induced tubular cell injury. Plasma from septic patients induced granulocyte adhesion, apoptosis and altered polarity in tubular cells. Plasma adsorption significantly decreased these effects and abated the concentrations of several soluble mediators. The inhibition of granulocyte adhesion to tubular cells was associated with the down-regulation of ICAM-1 and CD40. Resin adsorption inhibited tubular cell apoptosis induced by septic plasma by down-regulating the activation of caspase-3, 8, 9 and of Fas/death receptor-mediated signalling pathways. The alteration of cell polarity, morphogenesis, protein reabsorption and the down-regulation of the tight junction molecule ZO-1, of the sodium transporter NHE3, of the glucose transporter GLUT-2 and of the endocytic receptor megalin all induced by septic plasma were significantly reduced by resin adsorption. Septic plasma induced a direct injury of tubular cells by favouring granulocyte adhesion, by inducing cell apoptosis and by altering cell polarity and function. All these biological effects are related to the presence of circulating inflammatory mediators that can be efficiently removed by resin adsorption with a consequent limitation of tubular cell injury.Critical care (London, England) 01/2010; 14(1):R4. · 4.61 Impact Factor -
Article: 'Bench' MRI before transplant on harvested kidneys: a possible tool for diagnosis of acute pyelonephritis.
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ABSTRACT: We present the first case in which magnetic resonance imaging (MRI) has been utilized to rule out lesions compatible with acute pyelonephritis in kidneys from a cadaveric organ donor before transplanting them. A 40-year-old female underwent diagnosis of brain death following a septic shock. The ecotomography of the kidneys showed areas compatible with micro-abscesses raising the hypothesis of acute pyelonephritis. Our radiologist proposed to perform a bench-MRI (maintaining kidneys within the sterile preservation bags constantly on ice); this did not show lesions except little cysts not relevant by the clinical point of view. We transplanted kidneys without infective complications and results were very good.Nephrology Dialysis Transplantation 12/2008; 24(2):670-2. · 3.40 Impact Factor -
Article: Macrophage stimulating protein may promote tubular regeneration after acute injury.
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ABSTRACT: Macrophage-stimulating protein (MSP) exerts proliferative and antiapoptotic effects, suggesting that it may play a role in tubular regeneration after acute kidney injury. In this study, elevated plasma levels of MSP were found both in critically ill patients with acute renal failure and in recipients of renal allografts during the first week after transplantation. In addition, MSP and its receptor, RON, were markedly upregulated in the regenerative phase after glycerol-induced tubular injury in mice. In vitro, MSP stimulated tubular epithelial cell proliferation and conferred resistance to cisplatin-induced apoptosis by inhibiting caspase activation and modulating Fas, mitochondrial proteins, Akt, and extracellular signal-regulated kinase. MSP also enhanced migration, scattering, branching morphogenesis, tubulogenesis, and mesenchymal de-differentiation of surviving tubular cells. In addition, MSP induced an embryonic phenotype characterized by Pax-2 expression. In conclusion, MSP is upregulated during the regeneration of injured tubular cells, and it exerts multiple biologic effects that may aid recovery from acute kidney injury.Journal of the American Society of Nephrology 08/2008; 19(10):1904-18. · 9.66 Impact Factor -
Article: B cell positive cross-match not due to anti-HLA Class I antibodies and first kidney graft outcome.
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ABSTRACT: The effect of B cell cross-match (XM) was investigated in 680 first deceased-donor kidney transplants in a single centre from 1990 to 1999: 74 transplants presented a B-positive XM (Group 1) 606 had a B-negative XM (Group 2). The absence in Group 1 of weak/low-titre anti-HLA Class I antibodies was assured blocking anti-Class I reactivity by treating B cells with non-cytotoxic anti-beta2 microglobulin (alphabeta2 M) serum before XM. Graft survivals up to 5 years were not significantly different; some differences were nevertheless observed: HLA-A,B,DR mismatches influenced graft outcome in Group 1: patients with 0-2 mismatches had better survival than patients with 3-4. When analysed according DR mismatch, patients with 1 mismatch had worse graft survival than well matched patients (p<0.05). No significant difference depending on HLA match was observed in Group 2. Early acute rejection rate was similar in the Groups except the rejection episodes after one year: Group 1 had significantly more. 61/74 patients of Group 1 were retrospectively analysed for anti-HLA-DR,DQ reactivity: only 11/61 had anti-HLA-DR or DQ antibodies (3/11 were donor specific); graft survival and rejections were not significantly different in the patients with and without anti-HLA Class II antibodies. Anti-donor B cell reactivity, at XM, once excluded the presence of weak/low-titre anti-HLA Class I antibodies, did not influence first kidney graft survival.Transplant Immunology 07/2008; 19(3-4):238-43. · 1.46 Impact Factor -
Article: Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors
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ABSTRACT: ObjectiveTo test the hypothesis that extracorporeal therapy with polymyxin B (PMX-B) may prevent Gram-negative sepsis-induced acute renal failure (ARF) by reducing the activity of proapoptotic circulating factors. SettingMedical-Surgical Intensive Care Units. Patients and interventionsSixteen patients with Gram-negative sepsis were randomized to receive standard care (Surviving Sepsis Campaign guidelines) or standard care plus extracorporeal therapy with PMX-B. Measurements and resultsCell viability, apoptosis, polarity, morphogenesis, and epithelial integrity were evaluated in cultured tubular cells and glomerular podocytes incubated with plasma from patients of both groups. Renal function was evaluated as SOFA and RIFLE scores, proteinuria, and tubular enzymes. A significant decrease of plasma-induced proapoptotic activity was observed after PMX-B treatment on cultured renal cells. SOFA and RIFLE scores, proteinuria, and urine tubular enzymes were all significantly reduced after PMX-B treatment. Loss of plasma-induced polarity and permeability of cell cultures was abrogated with the plasma of patients treated with PMX-B. These results were associated to a preserved expression of molecules crucial for tubular and glomerular functional integrity. ConclusionsExtracorporeal therapy with PMX-B reduces the proapoptotic activity of the plasma of septic patients on cultured renal cells. These data confirm the role of apoptosis in the development of sepsis-related ARF.Intensive Care Medicine 01/2008; 34(9):1638-1645. · 5.40 Impact Factor -
Article: Potential risks of living kidney donation--a review.
Nephrology Dialysis Transplantation 12/2007; 22(11):3122-7. · 3.40 Impact Factor -
Article: Magnetic resonance imaging of gadolinium-labeled pancreatic islets for experimental transplantation.
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ABSTRACT: New imaging techniques that couple anatomical resolution to sensitivity may greatly contribute to improving islet transplantation. In the present work, a report is given of the direct detection of islets by magnetic resonance imaging (MRI) after ex vivo cell labeling with the MRI T(1) contrast agent GdHPDO3A. Experiments on mouse and human islets demonstrated well-tolerated uptake of GdHPDO3A, based on morphology, viability, glucose-dependent insulin response and apoptosis/toxicity gene array profile. GdHPDO3A loading was sufficient for in vitro MRI cell detection. In vivo isotransplanted mouse islets into the kidney capsule and xenotransplanted human islets within the mouse liver were detected. Imaging specificity was supported by the absence of signal in unlabeled islet transplants, its persistence upon using fat-suppression MRI protocols and the colocalization with the transplanted islets. In conclusion, direct islet imaging with high spatial and contrast resolution after labeling with GdHPDO3A is demonstrated, allowing visualization of kidney subcapsular mouse islet grafts and intrahepatic human islet xenografts.NMR in Biomedicine 03/2007; 20(1):40-8. · 3.21 Impact Factor -
Article: The long-term dialysis patient with purple-blue toes.
Nephrology Dialysis Transplantation 08/2006; 21(7):2022-3. · 3.40 Impact Factor -
Article: Grafted kidney, native kidney and proteinuria after pre-emptive pancreas-kidney transplantation: questions and answers.
Nephrology Dialysis Transplantation 05/2006; 21(4):1139-40. · 3.40 Impact Factor -
Article: Platelet-activating factor synthesis and response on pancreatic islet endothelial cells: relevance for islet transplantation.
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ABSTRACT: Recent data suggest that donor intraislet endothelial cells may survive islet transplantation and participate to the events that influence islet engraftment. However, the mechanisms that regulate islet endothelial behavior in this setting are poorly known. We obtained immortalized human (hIECs) and mouse (mIECs) islet endothelial cells by transfection with SV40-T-large antigen and studied the synthesis and response to Platelet-activating factor (PAF), a multipotent phospholipid that acts as endothelial mediator of both inflammation and angiogenesis. HIECs showed typical endothelial markers such as expression of vWF, CD31, and CD105, uptake of acetylated-LDL and binding to ULE-A lectin. Moreover, they expressed nestin, the PAF-receptor and possess surface fenestrations and in vitro angiogenic ability of forming tubular structures on Matrigel. Likewise, mIECs showed expression of vWF, CD31, nestin, PAF-receptor and CD105, and uptake of acetylated-LDL. HIECs and mIECs rapidly produced PAF under stimulation with thrombin in a dose-dependent way. Exogenous PAF or thrombin-induced PAF synthesis increased leukocyte adhesion to hIECS and mIECs and cell motility of both endothelial cell lines. Moreover, PAF or thrombin-induced PAF synthesis accelerated in vitro formation of vessel-like tubular structures when hIECs are seeded on Matrigel. Notably, gene-microarray analysis detected up-regulation of beta3 integrin gene on hIECs stimulated with PAF, that was confirmed at the protein level. Based on the novel development of immortalized islet endothelium, these results suggest that PAF may have a dual role that links inflammation to angiogenesis in the early events of islet transplantation.Transplantation 03/2006; 81(4):511-8. · 4.00 Impact Factor -
Article: Efficacy of an educational programme for secondary school students on opinions on renal transplantation and organ donation: a randomized controlled trial.
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ABSTRACT: Organ shortage for transplantation is a crucial problem; educational interventions may increase donations and decrease opposition. To test the efficacy of an educational programme on opinions on organ transplantation and kidney donation. Cluster Randomized Controlled Trial: eight intervention and eight control schools were randomly selected from the 33 public schools that agreed to participate. Targets: students in the last 2 years of secondary school (17-18 years); seven schools per group completed the study. EDUCATIONAL PROGRAMME: Intervention: first questionnaire (anonymous); 2 h lesson in each class; 2 h general session with patients and experts; second questionnaire. questionnaires. Differences between questionnaires (comparative analysis); interest; satisfaction with the programme; (cross-sectional analysis). 1776 first, 1467 second questionnaires were retrieved. Living kidney donation: at baseline 78.8% of students would donate a kidney to a relative/friend in need. The answers were unaffected by type of school but depended on sex (females more prone to donate, P<0.001); the answers did not change after the lessons. Cadaveric kidney donation: baseline opinions were mixed (intervention schools: 31.5% yes, 33.7% no, 34.8% uncertain), depending on type of school (classical-scientific high schools more positive than technical institutes, P<0.001), sex (males more prone to donate, P<0.001). Answers on living and cadaveric donation were correlated (P<0.001). The educational intervention increased favourable (31.5 to 42.9%) and uncertain (34.8 to 41.1%) opinions and decreased negative ones (33.7 to 16%) (P<0.001). Educational interventions are effective in increasing interest and improving opinions about cadaveric organ donation.Nephrology Dialysis Transplantation 03/2006; 21(2):499-509. · 3.40 Impact Factor -
Article: Cholesterol crystal embolism syndrome in dialysis patients: an emerging clinical diagnosis?
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ABSTRACT: Cholesterol crystal embolism syndrome (CCE) is an increasing end-stage renal disease cause. Few cases have been described on dialysis, despite the high prevalence of the predisposing factors. The diagnostic criteria of the present study were: skin lesions, myalgia, fatigue, fever and acute inflammatory serologic signs, in the presence of severe vasculopathy. The precipitating factors were: anticoagulation, endovascular intervention and ulcerated atherosclerotic plaque. Between October 2003 and September 2005, CCE was diagnosed in 6 dialysis patients (of 200-210 on chronic treatment): 5 males, 1 female, median age 59.5 years (47-70) and end-stage renal disease follow-up 11.5 years (3-25). All had severe vasculopathy, 5 cardiopathy, and 4 were failed graft recipients. The treatment included: peritoneal dialysis, daily dialysis, 'conventional' hemodialysis (2 cases) and hemodiafiltration. The diagnosis was based on the clinical-laboratory picture in 1 patient. In the 5 others clues were present (dicumarol therapy, angioplasty, femoral artery thrombosis, CCE predialysis and ulcerated aortic plaque). The therapeutic approach consisted of corticosteroids (5 cases), statins (4 cases) and prostaglandin analogues (4 cases). The differential diagnosis of CCE should also be considered in dialysis patients (necrotic lesions, limb pain and vasculitis-like signs).Blood Purification 02/2006; 24(5-6):433-8. · 2.10 Impact Factor -
Article: A dance teacher with kidney-pancreas transplant and diarrhoea: what is the cause?
Nephrology Dialysis Transplantation 09/2005; 20(8):1759-61. · 3.40 Impact Factor -
Article: Living life: mottos and logos on renal transplantation designed by high school students.
Nephrology Dialysis Transplantation 08/2005; 20(7):1307-10. · 3.40 Impact Factor -
Article: Quiz page. Acute infarction in a grafted kidney.
American Journal of Kidney Diseases 06/2005; 45(5):A49, e73-4. · 5.43 Impact Factor
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Institutions
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2002–2012
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Università degli Studi di Torino
- • Dipartimento di Scienze Mediche
- • Center for Experimental Research and Medical Studies
Torino, Piedmont, Italy
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