Papers by Maurizio Salvadori
Transplantation Proceedings, 1997
American Journal of Transplantation, 2004
In experimental models, the chemokine CXCL10/IP-10 is required for graft failure owing to both ac... more In experimental models, the chemokine CXCL10/IP-10 is required for graft failure owing to both acute and chronic rejection. In the present study, pretransplantation sera from 316 cadaver kidney graft recipients were tested for serum CXCL10 and CCL22/MDC levels by an ELISA assay. Kidney graft recipients with normally functioning grafts showed significantly lower serum CXCL10 levels than patients who experienced graft failure, whereas no differences for serum CCL22 levels were observed. After the assignment of all patients to four groups according to serum CXCL10 levels, the death-censored survival rates of grafts were 97.5%, 93.6%, 89.7%, 78.7% (p = = 0.0006) at 5 years, while no influence was observed on patient survival. Accordingly, patients with the highest CXCL10 levels showed an increased frequency and severity of rejection episodes. Serum C-reactive protein (CRP) level was also assayed in the same samples. Increase of serum CRP levels represented a predictive parameter for death, but not for graft failure. Multivariate analysis demonstrated that among the analyzed variables, CXCL10 had the highest predictive power of graft loss (RR 2.787). Thus, measurement of pretransplant serum CXCL10 levels might represent a clinically useful parameter to identify subjects who are at high risk of severe rejection and graft failure.
Transplantation, 2006
Background. Long-term success of renal transplantation depends upon the quality of the donor orga... more Background. Long-term success of renal transplantation depends upon the quality of the donor organ, avoidance of peritransplant and early posttransplant damage (rejection), and optimal maintenance of graft function after the first 6 -12 months. Glomerular filtration rate (GFR) at 1 year is a standard way to evaluate short-term success, whereas calculated GFR at 5 years gives a better appreciation of long-term outcomes. The objective of this study was to assess the effect of various demographic and transplant-related parameters on renal function via GFR at 1 year and 5 years post transplantation, using univariate and multivariate data analysis. Methods. Data on 1-year GFR were available from 10,397 patients, whereas 2,889 patients provided data on both 1-year and 5-year GFR. All patients were enrolled in the Neoral Multinational Observational Study in Transplantation (Neoral-MOST), an ongoing, prospective, observational study of adult renal transplant recipients. Results. One-year GFR was the most relevant predictor for 5-year GFR. In a multifactorial analysis (ANCOVA) using 1-year GFR as a continuous variable, the effects of several highly relevant parameters from univariate analysis (such as acute rejection and delayed graft function) on 5-year GFR appeared to be fully mediated by their influence on 1-year GFR, whereas immunological risk factors like HLA match or previous transplantation had an ongoing effect on graft function beyond year 1. Conclusions. The findings of this study corroborate and augment data from previous registry surveys, and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome.
Transplantation Proceedings, 2003
Background. Peritransplant risk factors influence short-term and long-term graft survival, and 1-... more Background. Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study-Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1-and 5-year renal function and their relationship to 1-year serum creatinine was assessed.
Transplant International, 2006
Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary ... more Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary nonfunction and delayed graft function (DGF) than heart beating cadaveric donor (CAD) kidneys, but little is known about long-term function of DCD grafts that survive to 1 year. To investigate the outcomes of renal transplant recipients whose DCD graft functioned for at least 1 year, this study analyzed data collected from 326 DCD graft recipients and 340 CAD-matched controls enrolled in a prospective, multinational, observational study – Neoral®-MOST (Multinational Observational Study in Transplantation) (Novartis, Basel, Switzerland). No differences were found in the demographics or immunosuppression between the two groups. All patients received a Neoral®-based immunosuppressive regimen. Donors after cardiac death graft recipients had a higher incidence of DGF (40% vs. 27% CAD; P < 0.001). One year glomerular filtration rate (GFR) and GFR-decline after 1 year were similar in DCD and CAD recipients (GFR 56 ml/min DCD vs. 59 ml/min CAD; GFR-decline −1.3 ml/min DCD vs. −1.4 ml/min CAD; P = not significant). Multifactorial analyses confirmed that GFR at 1 year was significantly influenced by donor age and gender, DGF, and acute rejection; however, DCD status was not an independent risk factor in cyclosporine-treated patients with grafts that had functioned for at least 1 year.
American Journal of Transplantation, 2004
on behalf of the ERL B301 Study Groups The introduction of mycophenolate mofetil (MMF) represente... more on behalf of the ERL B301 Study Groups The introduction of mycophenolate mofetil (MMF) represented a major advance in transplant medicine, although optimal use may be limited by gastrointestinal (GI) side-effects. An enteric-coated formulation of mycophenolate sodium (EC-MPS; myfortic ® ) has been developed with the aim of improving the upper GI tolerability of mycophenolic acid. Therapeutic equivalence of EC-MPS (720 mg b.i.d.) and MMF (1000 mg MMF b.i.d.), with concomitant cyclosporine microemulsion (Neoral ® ) and corticosteroids, was assessed in 423 de novo kidney transplant patients recruited to a 12-month, double-blind study. Efficacy failure (biopsyproven acute rejection [BPAR], graft loss, death or loss to follow up) at 6 months (EC-MPS 25.8% vs. MMF 26.2%; 95% CI: [− −8.7, + +8.0]) demonstrated therapeutic equivalence. At 12 months, the incidence of BPAR, graft loss or death was 26.3% and 28.1%, and of BPAR alone was 22.5% and 24.3% for EC-MPS and MMF, respectively. Among those with BPAR, the incidence of severe acute rejection was 2.1% with EC-MPS and 9.8% with MMF (p = = ns). The safety profile and incidence of GI adverse events were similar for both groups. Within 12 months, 15.0% of EC-MPS patients and 19.5% of MMF patients required dose changes for GI adverse events (p = = ns). Enteric-coated-MPS 720 mg b.i.d. is therapeutically equivalent to MMF 1000 mg b.i.d. with a comparable safety profile.
Transplantation Proceedings, 2005
2 For the NeoralMOST Study Group. Delayed graft function (DGF) is a frequent complication after r... more 2 For the NeoralMOST Study Group. Delayed graft function (DGF) is a frequent complication after renal transplantation, and may affect long-term graft function. The aim of this analysis was to evaluate risk factors for DGF, as well as parameters and events influencing graft function after DGF. Methods: MOST is a global observational study in transplant recipients with still functioning grafts receiving cyclosporine-microemulsion (CsA-ME) based regimens. The present analysis is based on patients with deceased donors, with information on DGF-status and data at 1 year post transplantation. Graft function was evaluated by GFR (Cockcroft-Gault estimate) normalized to the body surface area. Logistic regression and multifactorial analysis of covariance (ANCOVA) were used to assess the relevance of different predictive factors. Results: Amongst the 8950 patients included in the analysis, 2028 (23%) had experienced DGF. Multifactorial analysis identified a significant association with higher DGF incidence for longer CIT, older donors, PRA>10%, and male or Caucasian or overweight (BMI>25) recipients (p=60 mL/min/1.73m2 had younger donors and recipients, a higher proportion of male donors and recipients, and a lower incidence of AR or CMV compared to DGF-grafts achieving a less good function (p<0.001 for all). In a multifactorial analysis, the most relevant factors affecting 1-year renal function in DGF-patients were donor age and AR (p<0.001 for both), while CMV and other background parameters showed no independent effect. Conclusions: Acute rejections occur more frequently in DGF-patients, and are associated with lower renal function at 1 year. Preventing AR is an important element in strategies to achieve optimal outcomes of DGF-grafts.
Transplantation Proceedings, 1997
American Journal of Transplantation, 2004
In experimental models, the chemokine CXCL10/IP-10 is required for graft failure owing to both ac... more In experimental models, the chemokine CXCL10/IP-10 is required for graft failure owing to both acute and chronic rejection. In the present study, pretransplantation sera from 316 cadaver kidney graft recipients were tested for serum CXCL10 and CCL22/MDC levels by an ELISA assay. Kidney graft recipients with normally functioning grafts showed significantly lower serum CXCL10 levels than patients who experienced graft failure, whereas no differences for serum CCL22 levels were observed. After the assignment of all patients to four groups according to serum CXCL10 levels, the death-censored survival rates of grafts were 97.5%, 93.6%, 89.7%, 78.7% (p = = 0.0006) at 5 years, while no influence was observed on patient survival. Accordingly, patients with the highest CXCL10 levels showed an increased frequency and severity of rejection episodes. Serum C-reactive protein (CRP) level was also assayed in the same samples. Increase of serum CRP levels represented a predictive parameter for death, but not for graft failure. Multivariate analysis demonstrated that among the analyzed variables, CXCL10 had the highest predictive power of graft loss (RR 2.787). Thus, measurement of pretransplant serum CXCL10 levels might represent a clinically useful parameter to identify subjects who are at high risk of severe rejection and graft failure.
Transplantation, 2006
Background. Long-term success of renal transplantation depends upon the quality of the donor orga... more Background. Long-term success of renal transplantation depends upon the quality of the donor organ, avoidance of peritransplant and early posttransplant damage (rejection), and optimal maintenance of graft function after the first 6 -12 months. Glomerular filtration rate (GFR) at 1 year is a standard way to evaluate short-term success, whereas calculated GFR at 5 years gives a better appreciation of long-term outcomes. The objective of this study was to assess the effect of various demographic and transplant-related parameters on renal function via GFR at 1 year and 5 years post transplantation, using univariate and multivariate data analysis. Methods. Data on 1-year GFR were available from 10,397 patients, whereas 2,889 patients provided data on both 1-year and 5-year GFR. All patients were enrolled in the Neoral Multinational Observational Study in Transplantation (Neoral-MOST), an ongoing, prospective, observational study of adult renal transplant recipients. Results. One-year GFR was the most relevant predictor for 5-year GFR. In a multifactorial analysis (ANCOVA) using 1-year GFR as a continuous variable, the effects of several highly relevant parameters from univariate analysis (such as acute rejection and delayed graft function) on 5-year GFR appeared to be fully mediated by their influence on 1-year GFR, whereas immunological risk factors like HLA match or previous transplantation had an ongoing effect on graft function beyond year 1. Conclusions. The findings of this study corroborate and augment data from previous registry surveys, and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome.
Transplantation Proceedings, 2003
Background. Peritransplant risk factors influence short-term and long-term graft survival, and 1-... more Background. Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study-Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1-and 5-year renal function and their relationship to 1-year serum creatinine was assessed.
Transplant International, 2006
Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary ... more Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary nonfunction and delayed graft function (DGF) than heart beating cadaveric donor (CAD) kidneys, but little is known about long-term function of DCD grafts that survive to 1 year. To investigate the outcomes of renal transplant recipients whose DCD graft functioned for at least 1 year, this study analyzed data collected from 326 DCD graft recipients and 340 CAD-matched controls enrolled in a prospective, multinational, observational study – Neoral®-MOST (Multinational Observational Study in Transplantation) (Novartis, Basel, Switzerland). No differences were found in the demographics or immunosuppression between the two groups. All patients received a Neoral®-based immunosuppressive regimen. Donors after cardiac death graft recipients had a higher incidence of DGF (40% vs. 27% CAD; P < 0.001). One year glomerular filtration rate (GFR) and GFR-decline after 1 year were similar in DCD and CAD recipients (GFR 56 ml/min DCD vs. 59 ml/min CAD; GFR-decline −1.3 ml/min DCD vs. −1.4 ml/min CAD; P = not significant). Multifactorial analyses confirmed that GFR at 1 year was significantly influenced by donor age and gender, DGF, and acute rejection; however, DCD status was not an independent risk factor in cyclosporine-treated patients with grafts that had functioned for at least 1 year.
American Journal of Transplantation, 2004
on behalf of the ERL B301 Study Groups The introduction of mycophenolate mofetil (MMF) represente... more on behalf of the ERL B301 Study Groups The introduction of mycophenolate mofetil (MMF) represented a major advance in transplant medicine, although optimal use may be limited by gastrointestinal (GI) side-effects. An enteric-coated formulation of mycophenolate sodium (EC-MPS; myfortic ® ) has been developed with the aim of improving the upper GI tolerability of mycophenolic acid. Therapeutic equivalence of EC-MPS (720 mg b.i.d.) and MMF (1000 mg MMF b.i.d.), with concomitant cyclosporine microemulsion (Neoral ® ) and corticosteroids, was assessed in 423 de novo kidney transplant patients recruited to a 12-month, double-blind study. Efficacy failure (biopsyproven acute rejection [BPAR], graft loss, death or loss to follow up) at 6 months (EC-MPS 25.8% vs. MMF 26.2%; 95% CI: [− −8.7, + +8.0]) demonstrated therapeutic equivalence. At 12 months, the incidence of BPAR, graft loss or death was 26.3% and 28.1%, and of BPAR alone was 22.5% and 24.3% for EC-MPS and MMF, respectively. Among those with BPAR, the incidence of severe acute rejection was 2.1% with EC-MPS and 9.8% with MMF (p = = ns). The safety profile and incidence of GI adverse events were similar for both groups. Within 12 months, 15.0% of EC-MPS patients and 19.5% of MMF patients required dose changes for GI adverse events (p = = ns). Enteric-coated-MPS 720 mg b.i.d. is therapeutically equivalent to MMF 1000 mg b.i.d. with a comparable safety profile.
Transplantation Proceedings, 2005
2 For the NeoralMOST Study Group. Delayed graft function (DGF) is a frequent complication after r... more 2 For the NeoralMOST Study Group. Delayed graft function (DGF) is a frequent complication after renal transplantation, and may affect long-term graft function. The aim of this analysis was to evaluate risk factors for DGF, as well as parameters and events influencing graft function after DGF. Methods: MOST is a global observational study in transplant recipients with still functioning grafts receiving cyclosporine-microemulsion (CsA-ME) based regimens. The present analysis is based on patients with deceased donors, with information on DGF-status and data at 1 year post transplantation. Graft function was evaluated by GFR (Cockcroft-Gault estimate) normalized to the body surface area. Logistic regression and multifactorial analysis of covariance (ANCOVA) were used to assess the relevance of different predictive factors. Results: Amongst the 8950 patients included in the analysis, 2028 (23%) had experienced DGF. Multifactorial analysis identified a significant association with higher DGF incidence for longer CIT, older donors, PRA>10%, and male or Caucasian or overweight (BMI>25) recipients (p=60 mL/min/1.73m2 had younger donors and recipients, a higher proportion of male donors and recipients, and a lower incidence of AR or CMV compared to DGF-grafts achieving a less good function (p<0.001 for all). In a multifactorial analysis, the most relevant factors affecting 1-year renal function in DGF-patients were donor age and AR (p<0.001 for both), while CMV and other background parameters showed no independent effect. Conclusions: Acute rejections occur more frequently in DGF-patients, and are associated with lower renal function at 1 year. Preventing AR is an important element in strategies to achieve optimal outcomes of DGF-grafts.
Prima di analizzare un ritrovamento straordinario, qual è quello della strada etrusca del Frizzon... more Prima di analizzare un ritrovamento straordinario, qual è quello della strada etrusca del Frizzone, non si può fare a meno di disegnare, sia pure in sintesi, la storia del territorio in epoca etrusca e descrivere almeno i più importanti siti archeologici.
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Papers by Maurizio Salvadori