Mariano Ferraresso | Università degli Studi di Milano - State University of Milan (Italy) (original) (raw)

Papers by Mariano Ferraresso

Journal of Vascular Access, Jan 21, 2013

In this pilot study, we tested a newly developed electrospun multilayered, self-sealing graft, AV... more In this pilot study, we tested a newly developed electrospun multilayered, self-sealing graft, AVflo™, specifically designed for early hemodialysis access. Methods: ten eligible consenting patients had a polycarbonate-urethane graft (AVflo™) implanted and were followed up prospectively for at least six months. Performance measures included graft patency, complications and time to first cannulation. Mean age of the patients was 66.7 ± 10 years. chronic glomerulonephritis was the most common cause of renal failure. A total of 70% of the patients had a history of previous vascular access and 40% history of minimally invasive radiologic procedures for patency maintenance. In 40% of the cases the need for AV graft implantation was because of recurrent infections from permanent catheter for dialysis. Seven grafts were placed in the upper arm and three in the thigh. Mean follow up was 230 ± 75 days. Results: there were no systemic or local reactions to the graft and we did not report any graft infections. two grafts thrombosed because of severe bleeding post-cannulation due to an incorrect needle puncture. Both grafts were successfully thrombectomized. Primary and secondary patency rates at six months were 60% and 78%, respectively. these patency rates were comparable to those reported for other polyether-urethane and ePtFE grafts. Median time to first cannulation was seven days (3-21) and all puncture sites sealed in less than five minutes. Conclusions: this newly developed electrospun polycarbonate-urethane graft is safe in humans, permits early access obviating the need for venous catheters, and has equivalent patency as other prosthetic grafts.

Current Opinion in Organ Transplantation, 2016

Renal resistances correlate with histological scores and gradually decrease during hypothermic pu... more Renal resistances correlate with histological scores and gradually decrease during hypothermic pulsatile perfusion Renal resistances reduction is greater in kidneys with higher histological score Despite prolonged ischemia times perfused kidneys have a faster functional recovery that might translate in lower incidence of DGF, less need of dialysis, and shorter hospitalisations

Journal of Transplantation Technologies & Research, 2012

The polyomavirus JC virus (JCV) is a small nonenveloped DNA virus that asymptomatically infects a... more The polyomavirus JC virus (JCV) is a small nonenveloped DNA virus that asymptomatically infects about 80% of healthy adults and establishes latency in the kidney tissue. In case of immunodeficient hosts, JCV can lytically infect the oligodendrocytes, causing a fatal demyelinating disease, known as Progressive Multifocal Leukoencephalopathy (PML). Although the reactivation of another human polyomavirus, BK Virus (BKV), is relatively common and its association with the Polyomavirus Associated Nephropathy (PVAN) following renal transplantation is assessed, JCV replication and its impact on graft function and survival is less well studied. In addition, none of the performed studies ruled out the hypothesis that JCV could be associated with certain post-transplantation clinical syndromes. Thus, monitoring of Polyomaviruses infection, especially during the first 24 months post-transplantation, is recommended.

Transplantation, 2006

We investigate the effect of conversion from a cyclosporine (CsA) based-regimen to a tacrolimus (... more We investigate the effect of conversion from a cyclosporine (CsA) based-regimen to a tacrolimus (FK506)-based regimen with respect to graft renal function induced by chronic allograft nephropathy (CAN). Thirty-one patients with a histological diagnosis of CAN were included after other causes of chronic graft dysfunction had been excluded. Conversion to FK506 was undertaken at an initial dose of 0.15 mg/kg/d, which was subsequently adjusted to maintain FK506 whole blood trough levels between 5 and 10 g/L. The rate of decline of renal function before and after the FK506 conversion was represented by regression lines (slope) of the reciprocal of serum creatinine versus time. To evaluate the effect of conversion on allograft function, we gathered data on serum lipids, blood glucose, proteinuria, and hypertension. When postconversion slopes were compared to preconversion slopes for each patient, 20 patients (64.5%) showed positive regression lines and four patients (12.9%), less negative. Seven patients (22.6%) displayed an increased rate of decline in renal function with regression lines becoming more negative. FK506 was associated with a significant decrease in lipid levels, proteinuria, and hypertension. No patient returned to dialysis at the end of the 36-month follow-up. Conversion from a CsA-based regimen to a tacrolimus-based regimen was an effective alterative for salvage of patients with abnormal graft renal function induced by CAN.

Journal of Autoimmunity, 2007

Anti-phospholipid syndrome (APS) is defined by recurrent arterial/venous thrombosis and/or fetal ... more Anti-phospholipid syndrome (APS) is defined by recurrent arterial/venous thrombosis and/or fetal losses in the persistent presence of anti-phospholipid antibodies (aPL). In in vivo experimental models aPL thrombogenic activity is associated with a pro-inflammatory endothelial phenotype (increased adhesion molecule [ADM] expression and leukocyte adhesion) in addition to a pro-coagulant one (tissue factor [TF] expression). This is in line with the in vitro aPL ability to trigger intracellular signalling and to up-regulate ADM, TF and pro-inflammatory cytokine/chemokine expression at the mRNA and protein level in endothelial cells. Comparable effects were also reported in monocytes in vitro. In addition, complement activation is required by aPL to display their thrombogenic activity in in vivo models. Interestingly, complement activation blocking as well as Tumor Necrosis Factor alpha neutralization protect animals from aPL-induced fetal losses. Altogether these findings speak in favour for a role of inflammation in APS in spite of the absence of a clear inflammatory signature in the patients. We could not find any complement (C3c and C4d) deposition in the placentas from 2 late abortions (20 weeks of gestation) in APS women. Further studies are necessary to investigate whether complement activation and inflammatory processes found in animal models are taking place in APS patients.

Journal of Clinical Virology, Dec 1, 2014

Polyomavirus (PyV) infection is common, ranging from 60% to 100% depending on the virus. The urin... more Polyomavirus (PyV) infection is common, ranging from 60% to 100% depending on the virus. The urinary excretion rates of JC virus (JCV) and BK virus (BKV) have been extensively studied, but less is known about the more recently discovered PyVs. To investigate the urinary excretion of Merkel cell PyV (MCPyV), which is associated with Merkel cell carcinoma (MCC), in kidney transplant recipients and healthy subjects, as well as those of lymphotropic polyomavirus (LPV), which was isolated from the B-cells of African green monkeys but has also been found in human blood, JCV and BKV. Urine samples were collected from 62 adult (ATP) and 46 pediatric (PTP) kidney transplant recipients and from 67 adult (AHC) and 40 pediatric (PHC) healthy controls. DNA was isolated and analyzed using real-time PCR (Q-PCR) to determine the viral loads of MCPyV, LPV, JCV and BKV. MCPyV DNA was more frequently detected (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) in the PTP (36.9%) and PHC (30.0%) groups compared to JCV (8.7% in PTP, 12.5% in PHC), BKV (6.5% in PTP, 2.5% in PHC), and LPV (2.2% in PTP, 5% in PHC) and in the AHC (47.8%) group compared to BKV (13.4%) and LPV (0%). Based on the results, it could be concluded that: (a) Despite the rarity of MCC, MCPyV is a common infection; (b) MCPyV demonstrates an excretion pattern similar to those of JCV and BKV, persisting in the kidney and infecting skin cells upon reactivation, with subsequent integration and transformation.

Transplantation Proceedings, Nov 1, 2004

The argument for therapeutic drug monitoring (TDM) of cyclosporine (Cya) has been discussed for t... more The argument for therapeutic drug monitoring (TDM) of cyclosporine (Cya) has been discussed for the last two decades. So far, a generalized consensus has been reached for TDM of Cya microemulsion in adult transplant recipients, being Cya blood levels obtained 2 hours after the administration (C2), the most reliable in reflecting the overall Cya exposure. However, clear guidelines are not available for the pediatric population because of the distinct metabolism of the drug in this patient population. Therefore, adult data do not necessarily apply to children. In this retrospective analysis, the authors sought to define a universal parameter for pharmacokinetic clinical monitoring of Cya in long-term kidney transplant recipients, regardless of their age. Lower C2 levels were observed in all patients, adult and pediatric, who eventually developed chronic allograft dysfunction (CRAD) compared with patients who maintained stable kidney function throughout the entire follow-up (pediatric CRAD, 933 Ϯ 455 ng/mL; vs Stable, 1236 Ϯ 347 ng/mL, P ϭ .0001; and adult CRAD, 781 Ϯ 518 ng/mL; vs Stable, 1088 Ϯ 452 ng/mL, P ϭ .009). On the other hand, the risk of Cya underexposure was not highlighted by trough level monitoring (C0) because all patients have been maintained steadily on therapeutical C0 levels for the entire follow-up. In conclusion, for Cya maintenance therapy, C2 appears to be a superior strategy to C0 monitoring in both adult and pediatric kidney transplant recipients From the Division of Vascular Surgery and Organ Transplant (M.F., L.

Background: Human herpesvirus 6A (HHV6A) and 6B (HHV6B) are distinct species belonging to the Ros... more Background: Human herpesvirus 6A (HHV6A) and 6B (HHV6B) are distinct species belonging to the Roseolovirus genus. HHV6 is considered an ubiquitous virus and its worldwide sero-prevalence is approaching 100%. After the primary infection, HHV6 establishes latency in the host, mainly in peripheral blood monocytes (PBMCS) and may reactivate under immunosuppression conditions, such as transplantation. The presence of HHV6A/B genomes and its replication were investigated in blood samples collected from pediatric and young adult kidney transplant recipients. Materials and Methods: Peripheral blood samples were obtained from 55 pediatric (men age: 17.0 years) and 22 young adult patients (mean age: 29.7 years). The mean time from transplant was 74.8 months (range: 1\u2013 258 months). PBMCS and plasma were separated from blood and viral DNA was extracted. Polymerase Chain Reaction real time assay (q-PCR), targeting U67 region, was employed for the quantification of HHV6 genome in PBMCS. A nested PCR assay, able to differentiate HHV6A from HHV6B, was carried out. To discriminate the active replicating virus, both the presence of viral DNA in plasma samples and of the U100 and U67 transcripts in blood samples were analyzed by means of specific q-PCR and one step-reverse transcriptase PCR assays (RT-PCR), respectively. Results: The viral genome was detected in 16/77 patients (20.8%), with a mean viral load of 788.4 copies/ml (range: 61-1800 copies/ml). Ten out of 16 (62.5%) HHV6 positive patients were infected with the HHV6A. The viral genome was not detected in any of the tested clinical specimens, whereas the U100 and U67 transcripts were detected in one blood sample. No significant association was observed between the HHV6 infection, the patient\u2019s age, the time passed from the transplant, the HCMV co-infection and the clinical sympto. Conclusion HHV6 infection, even if frequently detected, seems not be associated with post transplant disorders in kidney transplant recipients

Pediatric Transplantation, Jun 1, 2005

Transplantation Proceedings, Jun 1, 2004

Tacrolimus-induced toxicity is considered a dose-related side effect largely due to a direct acti... more Tacrolimus-induced toxicity is considered a dose-related side effect largely due to a direct action of this potent calcineurin inhibitor on its targets including the kidney and the pancreas. This paper describes a case of tacrolimus systemic toxicity that appeared in a pediatric kidney transplant recipient who received a low drug dose. The kidney biopsy was a crucial aid toward the correct diagnosis, which reversed upon conversion to cyclosporinebased immunosuppression. A review of the literature suggests a chance of systemic toxicity even when the patient is maintained on therapeutic levels of tacrolimus. Because idiosyncratic reactions to the drug have not yet been postulated, we conclude that this suspicion may be addressed by a safe conversion to cyclosporine in pediatric patients.

Journal of Medical Virology, Jul 18, 2012

Transplantation Proceedings, Jul 1, 2008

Herein we report the outcomes of pediatric kidney recipients who underwent transplantation at lea... more Herein we report the outcomes of pediatric kidney recipients who underwent transplantation at least 10 years prior. A cohort of 36 patients (mean age, 26.4 Ϯ 6 years) with a mean follow-up time of 14.2 Ϯ 4 years was selected for the study. Immunosuppression consisted of cyclosporine and steroids. Actuarial patient and graft survivals 15 years after the transplantation were 97% and 86%, respectively. Only 1 patient died due to a complicated sclerosant peritonitis. Graft function was good with a mean serum creatinine of this selected cohort of 1.5 Ϯ 0.6 mg/dL. Eighteen percent were class 1, 33% class 2, and 49% chronic kidney disease. Hypertension was treated in almost 80% of the patients. The majority of patients were smaller than the average population with a final height (between 0 and Ϫ2) standard deviation score (HSDS) but only 27% had a severe growth impairment (HSDS ϾϪ2). Regarding nutritional status, fewer than 30% were overweight and only 1 patient was obese with a body mass index (BMI) Ͼ30. The majority of patients, except 2 mentally retarded individuals, are or have been attending normal school and achieved full-time employment. In conclusion, long-term survivors of a kidney transplant received during childhood reached a high degree of rehabilitation despite a long period of immunosuppression.

Transplantation, Jul 1, 2004

Journal of NeuroVirology, May 1, 2012

CXCR4 is a chemokine receptor constitutively expressed in the central nervous system, well charac... more CXCR4 is a chemokine receptor constitutively expressed in the central nervous system, well characterized for its homeostatic pro-survival effects on developing, as well as

Frontiers in Immunology

The wide-spread use of the anti-complement component 5 monoclonal antibody (moAb) eculizumab has ... more The wide-spread use of the anti-complement component 5 monoclonal antibody (moAb) eculizumab has greatly reduced the incidence of relapsing atypical hemolytic uremic syndrome (aHUS) after kidney transplantation (KT). However, the optimal management of aHUS transplant candidates with anti-Complement Factor H (CFH) antibodies remains debated. In these patients, the benefits of chronic eculizumab administration should be weighed against the risk of fatal infections, repeated hospital admissions, and excessive costs. We report the case of a 45-year-old female patient with CFHR1/CFHR3 homozygous deletion-associated aHUS who underwent deceased-donor KT despite persistently elevated anti-CFH antibody titers. As induction and aHUS prophylaxis, she received a combination of eculizumab and obinutuzumab, a humanized type 2 anti-CD20 moAb. The post-operative course was uneventful. After 1-year of follow-up, she is doing well with excellent allograft function, undetectable anti-CFH antibodies, s...

Tropical Medicine and Infectious Disease

Current knowledge on Leishmania infection after kidney transplantation (KT) is limited. In order ... more Current knowledge on Leishmania infection after kidney transplantation (KT) is limited. In order to offer a comprehensive guide for the management of post-transplant Leishmaniasis, we performed a systematic review following the latest PRISMA Checklist and using PubMed, Scopus, and Embase as databases. No time restrictions were applied, including all English-edited articles on Leishmaniasis in KT recipients. Selected items were assessed for methodological quality using a modified Newcastle–Ottawa Scale. Given the nature and quality of the studies (case reports and retrospective uncontrolled case series), data could not be meta-analyzed. A descriptive summary was therefore provided. Eventually, we selected 70 studies, describing a total of 159 cases of Leishmaniasis. Most of the patients were adult, male, and Caucasian. Furthermore, they were frequently living or travelling to endemic regions. The onset of the disease was variable, but more often in the late transplant course. The cli...

Transplant International, Sep 1, 2011

The purpose of this study was to compare the prognosis and the titers of anti-donor blood group a... more The purpose of this study was to compare the prognosis and the titers of anti-donor blood group antibody between different immunosuppressant protocols in ABO incompatible kidney transplantation (ABOiKTx). Method: One hundred twenty two recipients, who had ABOiKTx between March 1989 and January 2011, were enrolled in this study. 62 patients received azathioprine (AZA) with splenectomy (Spx) (AZA group), and 31 received mycophenolate mofetil (MMF) with Spx (MMF group), and 29 patients received MMF and rituximab (RIT) without splenectomy (RIT group). Graft survival and status of anti-donor blood group antibody were compared among three groups. Results: Overall graft survival rates were 90.3%, 100% and 95.7% at one year, 88.7%, 100% and 89.7 at three years, 78.6%, 96.6% and 89.7% at five years for AZA, MMF and RIT, respectively. MMF significantly improved graft survival (p=0.014). Figure 1 Anti-donor blood group antibodies were suppressed after Tx in all groups, compared to those before Tx Furthermore, RIT significantly suppressed anti-donor blood group antibody at one, two and four weeks and one month after Tx despite of non-Spx, compared to other two groups. Figure 2 Conclusion: MMF and RIT had beneficial effects on improving outcomes of ABOi KTx. MMF improved graft survival, and RIT inhibited donor specific antidonor blood group antibody production after ABOi KTx.

Medicina, 2022

Allograft vesicoureteral reflux (VUR) is a leading urological complication of kidney transplantat... more Allograft vesicoureteral reflux (VUR) is a leading urological complication of kidney transplantation. Despite the relatively high incidence, there is a lack of consensus regarding VUR risk factors, impact on renal function, and management. Dialysis vintage and atrophic bladder have been recognized as the most relevant recipient-related determinants of post-transplant VUR, whilst possible relationships with sex, age, and ureteral implantation technique remain debated. Clinical manifestations vary from an asymptomatic condition to persistent or recurrent urinary tract infections (UTIs). Voiding cystourethrography is widely accepted as the gold standard diagnostic modality, and the reflux is generally graded following the International Reflux Study Committee Scale. Long-term transplant outcomes of recipients with asymptomatic grade I-III VUR are yet to be clarified. On the contrary, available data suggest that symptomatic grade IV-V VUR may lead to progressive allograft dysfunction and...

Since their discovery back in the '70s, the human Polyomaviruses JCV and BKV have been for lo... more Since their discovery back in the '70s, the human Polyomaviruses JCV and BKV have been for long time the only members belonging to the Polyomaviridae family able to infect humans. During the last five years, at least ten other human Polyomaviruses have been discovered with similar structural and genomic characteristics of the progenitors BKV and JCV but with some differences in their tropism and pathogenesis. Generally, the primary exposure to all human Polyomaviruses that probably occurs during the first years of life, is frequently asymptomatic, but is always followed by the establishment of latency in several host's cells or tissues. The molecular and pathogenetic events associated with Polyomaviruses persistence and reactivations are not completely understood, whereas it is clear that viral reactivation is closely related to the host's immunological status. Based on these observations, organ recipients and in particular kidney transplant recipients are at risk of Pol...