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Vesicoureteral reflux (VUR) is a common urological complication in renal transplant patients., The Aim: of this study is to evaluate the performance of contrast-enhanced voiding urosonography (CEvUS) in the diagnosis and classification of reflux into the renal allograft, to evaluate and classify VUR into the allograft using voiding cystourethrography (VCUG) and CEvUS, to compare the two methods, and to propose a new classification of reflux into the allograft based on CEvUS and VCUG assessment, in line with the international reflux grading system., Materials and Methods:  From January 2017 to July 2019, 84 kidney transplant patients were enrolled. All patients underwent VCUG and CEvUS., Results:  In 76 cases there was agreement between VCUG and CEvUS (90 %) (Kappa = 0.7). The sensitivity of CEvUS using VCUG as the gold standard was 90 %, and the specificity was 92 %. Of the 7 cases diagnosed by VCUG and not by CEvUS, 6 were grade 1 and 1 was grade 2., Conclusion:  Transplant patients with reflux symptoms should undergo CEvUS. If the outcome is negative, VCUG should be performed. The classification that we propose is better suited to describe VUR in transplant patients, because it is simpler and takes into account whether reflux occurs not only during urination but also when the bladder is relaxed., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Few studies explored the role of hypothermic machine perfusion (HMP) in the sub-group of non-standard renal grafts with a biopsy-proven advanced histological impairment. This study aimed to investigate the role of HMP in grafts with a Karpinski Score >3 in terms of the need for dialysis, creatinine reduction ratio at day-7 (CRR7), and 3-year graft survival., Methods: Twenty-three perfused grafts with Karpinski Score >3 evaluated between November 2017 and December 2018 were retrospectively analyzed and compared with a control group of 32 non-perfused grafts transplanted between January 2014 and October 2017., Results: After transplantation, perfused grafts had fewer cases requiring dialysis (8.7% vs. 34.4%; p = 0.051), a better reduction in serum creatinine (median at 7 days: 2.2 vs. 4.3 mg/dl; p = 0.045), and shorter length of hospital stay (median 11 vs. 15 days; p = 0.01). Three-year death-censored graft survival was better in the perfused cases (91.3% vs. 77.0%; p = 0.16). In perfused grafts, initial renal resistance (RR) had the best predictive value for renal function recovery after the first week, as defined by CRR7 ≤ 70% (AUC = 0.83; p = 0.02). A cut-off value of 0.5 mm Hg/ml/min showed a sensitivity of 82.4%, a specificity of 83.3%, and diagnostic odds ratio = 23.4. After dividing the entire population into a Low-RR (n = 8) and a High-RR Group (n = 15), more cases with CRR7 ≤ 70% were reported in the latter group (86.7 vs. 13.3%; p = 0.03)., Conclusion: HMP yielded promising results in kidneys with Karpinski Score >3. Initial RR should be of interest in selecting non-standard organs for single kidney transplantation even in impaired histology., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Acute T-cell mediated rejection (aTCMR) is still an issue in kidney transplantation, for it is associated with chronic rejection, graft loss, and overall worse outcomes. For these reasons, a standard non-invasive molecular tool to detect is desirable to offer a simpler monitoring of kidney transplant recipients (KTRs). The purpose of our study was to examine, in peripheral blood before and after transplantation, the expression patterns of regulatory T cell (Treg)-related genes: the forkhead box P3 (FOXP3) and the two CTLA-4 isoforms (full-length and soluble) to predict acute rejection onset, de novo donor-specific antibodies (DSA) development and renal dysfunction 1 year after transplantation., Methods: We profiled by using a relative quantification analysis (qRT-PCR) circulating mRNA levels of these biomarkers in peripheral blood of 89 KTRs within the first post-transplant year (at baseline and 15, 60 and 365 days, and when possible at the acute rejection) and compared also the results with 24 healthy controls., Results: The three mRNA levels drastically reduced 15 days after transplantation and gradually recovered at 1 year in comparison with baseline, with very low levels at the time of aTCMR for FOXP3 (RQ = 0.445, IQR = 0.086-1.264, p = 0.040), maybe for the pro-apoptotic role of FOXP3 during inflammation. A multivariate Cox regression analysis evidenced a significant relation between aTCMR onset and thymoglobuline induction (HR = 6.749 p = 0.041), everolimus use (HR = 7.017, p = 0.007) and an increased risk from the solCTLA-4 expression at 15 days, mainly considering recipients treated with Mycophelolic acid (HR = 13.94 p = 0.038, 95%CI:1.157-167.87). Besides, solCTLA-4 also predisposed to graft dysfunction (eGFR< 60 mL/min/1.73m 2 ) at 1 year (AOR = 3.683, 95%CI = 1.145-11.845, p = 0.029). On the other hand, pre-transplant solCTLA-4 levels showed a protective association with de novo DSAs development (HR = 0.189, 95%CI = 0.078-0.459, p < 0.001)., Conclusions: mRNA levels of Treg-associated genes, mainly for solCTLA-4, in peripheral blood could put forward as candidate non-invasive biomarkers of cellular and humoral alloreactivity in clinical transplantation and might help shape immunosuppression, tailor monitoring and achieve better long-term outcomes of kidney transplantation in the wake of "precision medicine"., (© 2022. The Author(s).)

Solid organ transplant patients are at a higher risk for poor CoronaVirus Disease-2019 (COVID-19)-related outcomes and have been included as a priority group in the vaccination strategy worldwide. We assessed the safety and efficacy of a two-dose vaccination cycle with mRNA-based COVID-19 vaccine (BNT162b2) among 82 kidney transplant outpatients followed in our center in Rome, Italy. After a median of 43 post-vaccine days, a SARS-CoV-2 anti-Spike seroprevalence of 52.4% (n = 43/82) was observed. No impact of the vaccination on antibody-mediated rejection or graft function was observed, and no significant safety concerns were reported. Moreover, no de novo HLA-donor-specific antibodies (DSA) were detected during the follow-up period. Only one patient with pre-vaccination HLA-DSA did not experience an increased intensity of the existing HLA-DSA. During the follow-up, only one infection (mild COVID-19) was observed in a patient after receiving the first vaccine dose. According to the multivariable logistic regression analysis, lack of seroconversion after two-dose vaccination independently associated with patient age ≥60 years (OR = 4.50; P = .02) and use of anti-metabolite as an immunosuppressant drug (OR = 5.26; P = .004). Among younger patients not taking anti-metabolites, the seroconversion rate was high (92.9%). Further larger studies are needed to assess the best COVID-19 vaccination strategy in transplanted patients., (© 2021 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Chronic metabolic alterations such as post-transplant diabetes mellitus (PTDM), dyslipidaemias and overweight/obesity significantly impact on kidney transplant (KT) outcomes. This joint position statement is based on the evidence on the management of metabolic alterations in KT recipients (KTRs) published after the release of the 2009 KDIGO clinical practice guideline for the care of KTRs. Members of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID) selected to represent professionals involved in the management of KTRs undertook a systematic review of the published evidence for the management of PTDM, dyslipidaemias and obesity in this setting. The aim of this work is to provide an updated review of the evidence on the prevention, diagnosis and treatment of metabolic alterations in KTRs, in order to support physicians, patients and the Healthcare System in the decision-making process when choosing among the various available options., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Human leukocyte antigen (HLA)-G is a non-classical HLA molecule with immunomodulant and immunosuppressive functions, involved in transplantation tolerance. HLA-G14bp ins/del polymorphism in exon 8 has been associated with allograft rejection and kidney transplant outcome, with controversial results. We investigated associations of HLA-G14bp ins/del polymorphism on onset of some of the main post-transplant risk factors, like excess body weight, lipid abnormalities, increased fasting plasma glucose. Polymorphisms of cytokines with both immunosuppressive and metabolic effects were also assessed for comparisons and associated analysis., Methods: The present study involved kidney transplant recipients (n = 173) in which body mass index, cholesterol, triglycerides, fasting plasma glucose were registered in the first years after transplantation and analyzed in association with genotypes. Presence of hypertension and smoking habits, demographic, transplant-related and therapeutic data of patients were also recorded. Polymerase chain reaction, sequence-specific primer amplification and Taqman allelic discrimination techniques were used for genotyping of HLA-G14bp ins/del, interleukin (IL)-10(-1082G > A,-819 T > C,-592A > C), transforming growth factor-β(+ 869 T > C,+915C > G), IL-6(-174G > C), tumor necrosis factor-α(-308G > A) and IL-18(-137G > C,-607C > A). Effects of genotypes on clinical markers at each time point (pre-transplant and 1 to 5 years after transplant) were analyzed using a repeated-measures general linear model analysis; adjustment for potential confounders was performed., Results: Results showed that HLA-G14bp ins/ins was significantly associated with obesity, in particular after transplantation (3 years, p = 0.002, OR = 4.48, 95% CI:1.76-11.41). Post-transplant body mass index was significantly increased in HLA-G14bp ins/ins carriers (3 and 4 years, p = 0.033 and p = 0.044); effects of HLA-G14bp genotypes on post-transplant BMI were confirmed by using repeated-measures analysis and after controlling for confounding variables. Cytokine genotypes did not associate with the examined factors., Conclusions: The study of transplanted patients allowed to evidence a potential relationship between post-transplant weight gain and HLA-G14bp ins/del polymorphism, previously involved in rejection for its immunosuppressive/tolerogenic activity. This novel association could widen the knowledge of the role and functions of HLA-G molecules in diseases and transplantation.

Background: BK virus (BKV) infection represents a potentially dreadful complication after kidney transplantation (KT). When BK viremia is detected, the best therapeutic approach remains not entirely clarified. Critical elements of BK viremia treatment are immunosuppression minimization and introduction of drugs like leflunomide, everolimus, and fluoroquinolones. The study aimed to analyze the results of the BK viremia management in 2 collaborative Italian centers., Methods: Ten patients undergoing KT in the 2 collaborative Italian centers of Sapienza University of Rome and University of L'Aquila from January 2013 to December 2017 and showing a post-KT diagnosis of BK viremia were retrospectively investigated., Results: Mean time from KT to BKV positivity was 7 months (range: 1-19 months). At diagnosis, the mean viral load was 683,842 copies/mL (range: 5800-4,052,415 copies/mL), with an average zenith of 2,428,410 copies/mL (range: 6762-18,022,500 copies/mL). In the 5 patients with BKV nephropathy, we observed a switch from antimetabolite to leflunomide (n = 5), a switch from tacrolimus to everolimus (n = 3), or an introduction of fluoroquinolones (n = 3). BKV clearance was achieved in 3 patients., Conclusions: Early BKV diagnosis and stepwise minimization of immunosuppression remain the first-line approach in patients with BK viremia. In the presence of BKV nephropathy, a combination of antiviral drugs like leflunomide and fluoroquinolones/everolimus should favor viremia clearance., (Copyright © 2019. Published by Elsevier Inc.)

Background: Arterial vascular anomalies in patients undergoing kidney transplantation (KT) are correlated with a higher incidence of early surgical complications, potentially causing graft loss. Arterial reconstruction allows patients to overcome these surgical challenges, thus minimizing the risk of poor outcomes. The aim of the present study is to retrospectively investigate the safety and effectiveness of the multiple arterial reconstruction technique with a Teflon patch in case of an unavailable aortic patch: to do so, surgical complications, graft function, and patient survival were evaluated., Methods: During the period January 2009 to August 2016, 202 adult deceased-donor KTs were performed at our center. Group A (n = 27; reconstruction of multiple arteries) and Group B (n = 175; control group) were compared., Results: No differences were observed between the 2 groups in terms of early postoperative course, with no vascular complication observed in Group A. No vascular patch infections were reported, nor longer cold ischemia time rates. Similarly, long-term survival rates were similar between the 2 groups., Conclusions: The Teflon-patch arterial reconstruction technique appears to be safe and effective, with an acceptable balance of benefits and potential risks of using a prosthetic material. Studies based on larger series are needed to further validate this approach., (Copyright © 2018. Published by Elsevier Inc.)

Background: BK virus (BKV)-associated nephropathy is definitely involved in allograft failure after kidney transplant. Thus, the need for an early control of viral reactivation in immunocompromised patients is well established. Determination of urinary release of decoy cells (DC) and BK viral load in plasma and urine by polymerase chain reaction (PCR) usually precedes renal biopsy. The aim of the study is to assess viral reactivation by BKV-DNA PCR and DC detection in urinary sediment using automated intelligent microscopy., Methods: Seventy-eight kidney transplant patients were analyzed for the presence of plasma BKV-DNA by quantitative TaqMan real-time PCR. Additionally, automated intelligent microscopy was used for urine sediment analysis, allowing to count cells with decoy feature, confirmed by phase contrast microscopic review., Results: Plasma BKV-DNA PCR was detected in 14 (17.9%) patients. DC were identified in 19 (24.3%) urine sediments by automated analyzers and confirmed by microscopic observation. Two patients were BKV-DNA-positive/DC-negative; conversely, 7 subjects were DC-positive/BKV-DNA-negative., Conclusions: Plasma quantification of BK viral load is currently the best noninvasive method for the detection of viral reactivation. Nevertheless, automated methods to screen for the presence of DC in urine could facilitate early BK virus replication diagnosis and patient follow-up by quantitative and visual results., (Copyright © 2018. Published by Elsevier Inc.)

The fat mass and obesity-associated (FTO) gene is one of the most important obesity susceptibility genes. Some FTO gene polymorphisms have been associated with obesity, diabetes, and hypertension, all conditions for which, after transplant, there is increased susceptibility, due to effects of immunosuppressive regimens. To evaluate whether FTO could be a candidate for targeted preventive intervention in the transplant setting, we investigated whether the common genetic variation, FTO rs9939609T>A, could affect weight gain and risk of cardiovascular complications in kidney transplantation., Methods: In 198 kidney transplant recipients, FTO rs9939609 was investigated in association with body mass index (BMI)/obesity and with other clinical markers of posttransplant risk, then monitored up to 5 years after transplantation. Genotyping was performed using an allelic discrimination method on a real-time polymerase chain (PCR) system. Associations were analyzed using the chi-square test; differences between genotypes were examined with analysis of variance or Kruskal-Wallis test; tests for repeated measures and a general linear model analysis controlling for age and gender were also utilized., Results: Allele and genotype frequencies of FTO rs9939609 in recipients (T/T, 29.8%; T/A, 49.0%; A/A, 21.2%; A, 45.7%; T, 54.3%) reflect those present in healthy Caucasian populations. In the face of pre-/posttransplant differences in total cholesterol, triglycerides, or fasting glucose, results did not show significant changes in these factors among genotypes either before or after transplantation., Conclusion: This study highlights a lack of association of FTO rs9939609T>A genotypes and posttransplant weight gain, plasma lipids, and fasting blood glucose in kidney transplantation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Cytomegalovirus (CMV) represents the leading cause of viral infection in kidney transplantation patients. The aim of the present study was to evaluate the efficacy and safety of pre-emptive anti-CMV therapy., Materials and Methods: We performed a retrospective analysis based on data from 227 consecutive patients transplanted from 2010 to 2015, of whom 38 (16.6%) were from a living donor, considering: incidence of rejection, CMV organ localization, and graft and patient survival. All patients underwent induction immunosuppressive therapy followed by maintenance therapy consisting of corticosteroids, antimetabolites, and tacrolimus (median basal dose = 5.3 ng/mL). The timing for the detection of plasma CMV-DNA in the post-transplantation period was: weekly (first month), quarterly (second through twelfth month), and then half-yearly., Results: CMV viremia was positive in 98 of 227 (43.1%) patients, with an average of 248,482 copies/mL (range: 250 copies/mL to 9,745,000 copies/mL) and the first positivity after a median period of 2.5 months from kidney transplantation (range: 0.2 months to 43 months). A total of 49 of 227 (21.5%) patients were treated with antivirals: 27 of 49 (55.1%) because of CMV organ localization (gastrointestinal = 20, lungs = 3, kidney = 2, liver = 2). Fourteen of 227 (6.1%) patients had a rejection episode, 7 (3.1%) of which were CMV-related. Fifteen of 227 (6.6%) patients died (noninfectious CMV-related complications = 8, cardiovascular causes = 6, bleeding complications = 1)., Conclusion: Our experience confirms the validity of the pre-emptive anti-CMV therapy in renal transplantation patients., (Copyright © 2017. Published by Elsevier Inc.)

Impaired would healing is a known adverse effect of chronic immunosuppression. Solid-organ transplant recipients undergoing major abdominal surgery have an increased risk of wound-related complications compared with the general population. In this subset of patients, surgical site infections and wound dehiscence must be aggressively treated to avoid sepsis, graft loss, and death. Recently, topical application of platelet-rich plasma has been proposed as an alternative therapeutic option to enhance wound healing in difficult cases. Unfortunately, randomized controlled trials evaluating the efficacy of platelet-rich plasma compared with standard or advanced wound management are lacking, and the literature mostly refers to anecdotal reports in patients with no evidence of wound infection. This report documents a kidney transplant recipient who experienced spontaneous bladder rupture because of gangrenous cystitis. After an exploratory laparotomy and bladder repair, the patient developed a deep surgical site infection by multidrug resistant Acinetobacter baumannii and extensive wound dehiscence. Advanced wound management and vacuum-assisted closure therapy were ineffective. Topical homologous platelet-rich gel was used resulting in significant wound healing, without infections or immunologic complications.

Background: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time., Methods: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency., Results: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively., Conclusions: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Introduction: Immunosuppressive protocols containing everolimus (EVR) preserve good renal function in kidney transplantation (KT), although they are often complicated by several adverse events. We have evaluated the efficacy and safety of a protocol with late (1 month after KT) EVR introduction., Material and Methods: This study randomized 49 de novo patients undergoing KT between September 2012 and June 2014 into 2 groups: group A (n = 24) with late EVR introduction and tacrolimus reduction, and group B (control group; n = 25) with a standard immunosuppressive regimen. Primary aims were 1-year patient and graft survivals and acute rejection rates. Secondary aims were related to wound, metabolic, and hematologic complications., Results: Patient and graft survivals were similar in both groups. One year after KT, median serum creatinine was inferior in group A (1.4 vs 1.8 mg/dL; P = .004). Late acute rejection (8.3 vs 12.0%; P = 1.0) and wound complication (4.2 vs 4.0%; P = 1.0) rates were similar. Higher cholesterol and triglycerides and lower platelets and hemoglobin levels were observed in group A., Conclusions: In our experience, delayed introduction of EVR shows similar results with respect to its early introduction, contemporaneously presenting fewer wound complications and lymphoceles. A higher rate of metabolic and hematologic complications are, however, observed in patients under EVR therapy. Further multicenter studies should be performed to confirm these preliminary results., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Functional polymorphisms of molecules involved in immune-mediated mechanisms of allograft rejection could be predictive of increased risk for early and late post-transplant complications. In the past years, the challenge for long-term graft survival in kidney recipients is the implementation of personalized approaches. In this study, effects of interleukin (IL)-18-137G/C (rs187238), -607C/A (rs1946518), and other pro-inflammatory cytokine gene polymorphisms (tumor necrosis factor [TNF]-α-308G/A, rs1800629, IL-6-174G/C, rs1800795, and interferon [IFN]-γ+874A/T, rs2430561) on the main post-transplant risk parameters and diseases (metabolic, cardiovascular, infective, and chronic allograft rejection) were assessed in kidney-transplanted patients., Methods: One hundred seventy-nine transplanted patients were retrospectively analyzed for clinical and biochemical parameters and onset of post-transplant complications. Taqman allelic discrimination and PCR-SSP (polymerase chain reaction-sequence specific primers) techniques were used for genotyping., Results: No predictive effects of allele and genotypes of IL-18-607C/A, TNF-α-308G/A, IL-6-174G/C, and IFN-γ+874A/T gene polymorphisms and onset of risk factors and late complications were evidenced. However, Kaplan-Meier analysis evidenced a weak effect of IL-18-137G/C genotypes on graft survival., Conclusions: Analyzing associations between some pro-inflammatory cytokine gene polymorphisms and onset of the most relevant risk factors and late complications of kidney transplant, results suggested a possible impact of IL-18-137G/C genotypes on graft survival, which deserves further studies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Viral myocarditis can emerge with various symptoms, including fatal arrhythmia and cardiogenic shock, potentially evolving in chronic myocarditis or dilatative cardiomyopathy. We report a case of a kidney transplant patient affected by coxsackie viral myocarditis., Methods: A 49-year-old man was admitted to our hospital with dyspnea and fever in August 2014. He underwent living donor kidney transplantation in 1986 and polar graft resection for papillary carcinoma in 2012., Results: The initial investigation showed pulmonary congestion, pancreatitis, increased serum troponin I, and increased liver enzyme levels. Echocardiogram revealed an ejection fraction (EF) of 20% and PAPS 45 mm Hg. He underwent coronary stent implantation, started hemodialysis, and continued on low-dose steroid immunosuppressive therapy. The clinical course improved rapidly, but endomyocardial biopsy showed acute myocarditis. Further investigation revealed a high antibody titer against coxsackievirus B4 and B5. Pancreatic enzyme levels normalized 2 months after patient admission; his cardiac condition improved after 6 months. The patient has been followed for 1 year, and his left ventricular EF is stable (45%)., Conclusions: Viral myocarditis represents a serious clinical condition requiring a fast therapeutic intervention. This patient's clinical course suggests that changes in his immunosuppressive therapy were associated with progressive amelioration of his viral myocarditis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Coupled plasma filtration adsorption (CPFA) is an extracorporeal treatment based on plasma filtration associated with an adsorbent cartridge and hemofiltration. CPFA is able to remove inflammatory mediators and it has been used to treat severe sepsis, septic shock and multiple organ dysfunction syndrome. Limited experience exists on the use of CPFA after solid organ transplantation. We report our experience with CPFA in 2 kidney transplant recipients with post-nephrolithotomy septic shock and severe unexplained rhabdomyolysis. In both the cases, excellent results were observed. In selected cases, CPFA can be safely and effectively used in patients with a solid organ transplant. However, additional studies are needed in this particular setting, to further investigate the potential role of CPFA for the treatment of other conditions associated with excessive inflammation, such as in rheumatologic disorders and delayed graft function., (© 2015 The Author(s) Published by S. Karger AG, Basel.)

Introduction: Spontaneous kidney allograft rupture (KAR) is a rare but potentially life-threatening complication after kidney transplantation. It is associated with a high risk of graft loss and patient death. We report a new technique of surgical repair in case of KAR., Case Report: A 53-year-old man transplanted due to diabetic nephropathy-related end-stage renal disease experienced a spontaneous KAR 10 days after KT. Immediate laparotomy revealed the presence of a 4-cm linear kidney fracture. Dexon 2-0 wires were used for the suture, stopping each wire with Hem-o-Loks on a cylinder of oxidized cellulose gauze, with the intent of avoiding the risk of tissue fracture caused by the suture itself. Bleeding was thus controlled. The patient experienced an uneventful course and was discharged on postoperative day 26., Conclusions: According to the recent literature, graft nephrectomy for KAR is no longer considered the standard surgical treatment. A new approach to rupture repair has been proposed, providing good rates of graft and patient survival., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We report the surgical management of a bilateral renal artery aneurysm diagnosed in a 41-year-old patient with a history of recurrent abdominal pain. The preoperative contrast-enhanced computed tomography showed a complex saccular aneurysm on both renal arteries within the renal hilum. The characteristics of aneurysms precluded endovascular procedures, and a double-step bilateral ex vivo reconstruction with kidney autotransplantation was planned. The intra- and postoperative period was uneventful. Imaging and laboratory examinations show preservation of renal function, and patient is symptom-free at 10-month follow up., (© 2013 The Japanese Urological Association.)

The fundamental role of antibodies in the development of acute graft rejection has been established recently. Antibody-mediated acute rejection may develop at any time during the post-transplant period. Several therapeutic approaches have been proposed in the last decades. However, there is no standardized therapy. The aim of this study is to report the Sapienza University experience of combined plasma treatment and high-dose intravenous immunoglobulin ± extracorporeal photopheresis. From January 2006 to September 2009, 6 patients were treated at Sapienza University. In 5 cases (83%) complete regression of the acute rejection was observed, followed by stable renal function (median creatinine value at 1-year follow-up: 1.5 mg/dL). No adverse events were reported. Our approach seems to give good results in terms of graft survival and procedure safety. Further studies on a larger number of patients will be needed to confirm the validity of these findings. Moreover, comparison between our protocol and other treatments is necessary.

Background: Recently, the role of antibodies has been documented in the development of acute rejection episodes. Antibody-mediated acute rejection (AMAR) may develop at any time after transplantation, with an incidence of almost 7%. Several therapeutic approaches have been proposed in the past decades. However, no data exist regarding combined plasma treatment (PT) and extracorporeal photopheresis (ECP). The aim of this study was to report an initial single-center experience of combined PT and ECP with high-dose intravenous immunoglobulin (IVIg) for the treatment of AMAR., Methods: Three patients were treated with this approach., Results: In 2 cases, we observed immediate restoration of graft function, and in 1 case, in which we interrupted the protocol owing to lack of patient consent, the graft was lost. No organ infections were reported during the therapy period. The rationale for use of ECP is related to the presence of mixed antibody and cell-mediated mechanisms in acute rejection episodes. ECP inhibits specific pathogenic T cells., Conclusion: Our approach seemed to give good results in terms of graft survival and safety., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Use of expanded-criteria donors (ECDs) for kidney transplantation has progressively increased in the past years with the intent to improve the number of available grafts. However, it is still uncertain if ECD kidneys have worse survivals than standard-criteria ones. The aim of this study was to retrospectively analyze a cohort of ECD patients comparing the 2 subgroups of 50-59- and >60-year-old donors in terms of donor, recipient, and transplant features and survival rates., Methods: Ninety-one cases were analyzed. The cohort was stratified into 2 subgroups according to donor age: group 1, age 50-59 years (n=26); and group 2, age ≥60 years (n=67)., Results: Group 2 represented older donors and a higher percentage of donors with a previous history of hypertension. In Group 1, preharvest creatinine values showed higher results. No difference was detected regarding patient and graft survivals, with 5-year survival rates of 92.3% versus 86.7%, and 70.8% versus 69.8%, respectively. The best way to select the donors is still under debate. In our experience, a biopsy-driven selection was performed exclusively for group 2 ECDs. Considering the similar survivals obtained, we speculated that an accurate biopsy-based selection of older grafts allows one to avoid "bad" donors from the allocation system, thereby obtaining improved survival results., Conclusions: Biopsy-driven pretransplantation selection appears to be the main system to optimize results, to achieve outcomes similar to nonbiopsied younger donors. Routine biopsies also in the younger subgroup of ECD may achieve a further improvement in survival., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Numerous evidence has been reported to support a safe 1:1 conversion from the twice-daily tacrolimus (Tac-T) to the once-daily tacrolimus regimen (Tac-O), but frequently there is a reduction in drug trough levels, which has been estimated by some authors to be about 20%. The relationship between Tac-O dosage and trough levels after conversion is not clear. The tacrolimus trough levels-to-dose ratio has been applied to better define the wide variability in doses and blood levels of tacrolimus. The aim of this study was to evaluate tacrolimus trough levels, tacrolimus daily dosage, and tacrolimus level-to-dose ratio during 1 year pre-postconversion follow-up in 31 stable kidney transplant patients who had received Tac-T therapy for over 6 months with stable renal function. They were converted to the same dosage of Tac-O. Patients before and after conversion were their own controls. The trough levels of tacrolimus showed a slight albeit significant reduction after conversion, remaining in the therapeutic range. Nineteen percent underwent an adjustment in total daily dosage after conversion versus 39% before conversion with no significant difference. No significant differences were detected in the total daily dose administered either by tacrolimus level-to-dose ratio before or after conversion. Kidney transplant recipients under Tac-O therapy were safely maintained using the same therapeutic monitoring as when receiving Tac-T., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: In kidney transplantations, the identification of early postoperative parameters with high predictive power for the development of late allograft dysfunction has important implications for clinical practice. This study sought to determine these parameters in a single-center cohort., Methods: We studied 82 deceased donor renal transplantation. We assessed the following measures: dialysis-dependent delayed graft function (ddDGF), extended DGF, serum creatinine level at day 7, creatinine reduction ratio at day 7, urine output at day 1 and at day 7 posttransplantation (UO7)., Results: Only UO7 showed a significant result upon multivariate analysis (P < .0001). It was less influenced by dialysis with respect to measures based upon serum creatinine. By Receiver Operating characteristic (ROC) analysis, it showed an elevated area under the curve (0.811), with a cut-off value of 500 mL/24 h, showing high sensitivity (98.5%)., Conclusions: UO7 may be of clinical utility to assess the risk for subsequent renal dysfunction., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Analysis of the anti-HLA antibody status of 100 recipients of kidneys from deceased donors demonstrated that presensitization and the development of alloantibodies after transplantation are associated with the development of antibody mediated as well as cellular rejection. This finding indicates that the humoral arm of the immune response is also involved in cell-mediated rejection and/or that there may be a continuum between these two forms of rejection. Most episodes of rejection were successfully reversed in our population, as shown by the overall 3-year actuarial survival of 98% in nonsensitized and 91% in sensitized recipients, emphasizing the importance of comprehensive antibody studies.

Use of expanded criteria donors (ECD) has increased worldwide in previous years because of the donor scarcity. However, ECD are related to a greater risk of complications and shorter graft longevity. Delayed graft function (DGF) which impacts renal graft survival, represents one of the most common complications posttransplantation. The purpose of this study was to analyse DGF incidence among ECD kidneys and its role on early and intermediate recipient and graft survivals. We prospectively analyzed 46 ECD cases divided as group A (absence of DGF; n = 23) and B (DGF; n = 23). Group B was composed of older donors (P = .033) with longer cold ischemia times (P = .017), and greater incidences of acute rejection episodes (ARE) (P < .0001). Comparing group A with group B, we observed 1-year and 3-year overall recipient survivals to be 95.7% and 95.7% versus 91.3% and 91.3%, respectively (P = not significant). Censored 1-year and 3-year overall graft survivals were 100% and 92.9% versus 85.6% and 79.9%, respectively (P = .026). Analyzing the patients with DGF without (n = 9) versus with concomitant ARE (n = 14), no differences were noted in recipient and graft survivals. The incidence of DGF was strictly related to increased donor age, greater cold ischemia time, and presence of an ARE while DGF did not have a role in recipient survival, it reduced, graft survival. Concomitant ARE was not related to an impaired graft function.

Delayed graft function (DGF) represents one of the most common complications after kidney transplantation. The increased use of expanded criteria donors (ECD) is related to a greater risk for DGF. The objective of our study was to analyze the incidence of DGF among ECD versus standard criteria donors (SCD). Among 121 cases we obtained 2 groups: group A (SCD; n = 75) and group B (ECD; n = 46). Group B was composed of older donors (P < .0001), with an increased incidence of diabetes mellitus (DM; P < .0001), arterial hypertension (AH; P < .0001), cerebrovascular accidents (P = .013), and lower creatinine clearances (CrCl; P = .008). Recipient age was significantly lower among group A (P < .0001), with an increased incidence of donor hypotensive episodes (P = .016). The global incidence of DGF was 40 patients (33%), who were mainly in group B (P = .004). Analyzing the entire population, donor age >or= 60 years (P = .005), CrCl < 40 mL/min (P = .025), donor history of DM (P = .026) and AH (P = .017), and cold ischemia time > 15 hours (P < .0001) were parameters related to increased incidences of DGF. A biopsy score of 3 was not significantly associated with DGF. The results of our study underlined the increased risk for DGF related to the use of ECD. Donor age >or= 60 years and cold ischemia time > 15 hours showed strong associations with this complication.

Incidence of cardiovascular complications, cancers and chronic allograft nephropathy (CAN) suggests reduction of immunosuppressive dosages. Some studies analyzed the effects of minimization of immunosuppression until the avoidance of immunosuppressive drugs. However minimization seems to be related to a higher incidence of acute rejection. Induction of tolerance after transplantation and use of immunological tests that could monitor the immune reactivity are required. The aim of this study is to evaluate immunological state in a group of recipients after deceased and living donor kidney transplantation and to minimize immunosuppressive therapy monitoring simultaneously clinical and immunological parameters. We analyzed 41 patients, 38 from deceased donors and 3 from living donor kidney transplantation. All patients were treated with triple immunosuppressive therapy: cyclosporine or sirolimus or tacrolimus, mycophenolate mofetil and steroids. In all recipients the presence of CD8+CD28- T suppressor cells (Ts) was analyzed. Patients were divided in 2 groups, according to the presence of Ts. In patients with Ts, (Group A, n=19), mycophenolate mofetil (MMF) was progressively reduced and then stopped. Steroids were subsequently reduced and then interrupted, maintaining an immunosuppressive therapy with low doses of calcineurin inhibitors (CNI) or sirolimus (SIR). 22 patients were without presence of Ts: we enrolled for the study only patient acute rejection free, without proteinuria and with creatinine levels stable (Group B, n=19). In these patients, MMF was reduced and then stopped, while steroids were decreased to 5 mg at alternate days, maintaining CNI or SIR at medium therapeutic dosages (minimized therapy). Patient and graft overall survival in Group A and in Group B were respectively at 100% and 94.7%. Incidence of acute rejection was respectively at 0% in group A and 15.7% in Group B. Presence of episodes of acute rejection in Group B confirms risk of later minimization of steroids and the relevance of the analysis of recipient immunological reactivity before modification of immunosuppressive therapy. A careful evaluation of recipient immune reactivity with the presence of T regulatory cells can allow adequate and personalized immunosuppressive regimens, without high risks of acute rejection.

Polycystic disease causes a progressive decrease in renal function and liver degeneration. The progression of the disease evolves separately between organs and transplantation options vary: simultaneous or sequential liver-kidney transplantation or single-organ transplantation. From September 2006 to June 2007 3 combined liver kidney transplantations (CLKT) were performed for polycystic disease with end-stage renal disease: 2 with polycystic liver disease, and 1 with hepatic failure due to congenital hepatic fibrosis. The widest dimensions of the polycystic liver of 50 and 60 cm diameter were due to extensive cystic degeneration. We performed 1 simultaneous CLKT and 2 sequential transplantations: 1 liver after kidney, and 1 kidney after liver. At present all patients are alive with 100% graft function. Median creatinine level at discharge was 0.9 mg/dL (ranges, +/-0.2). Good liver graft function was reported in all 3 cases. Transplant benefit in polycystic liver-kidney disease has been already demonstrated; conservative surgical options may result in a high incidence of complications in highly involved polycystic livers. Delaying transplantation results in a more difficult surgical technique, a higher rate of postoperative complications, and a disturbance of optimal graft retrieval because of the worse preoperative condition of the patients.

In patients with end-stage chronic kidney disease (CKD) and type 1 diabetes mellitus (DM 1), simultaneous pancreas-kidney (SPK) transplantation is currently considered the gold standard therapy. The aim of this study was to analyze and report the long-term clinical outcomes of the 23 SPK transplantations performed at our institution over an 84-month period (January 1, 2000 to December 31, 2006). A prospective analysis of these patients included donor, recipient, and transplantation characteristics. The only requirements for transplantation were blood group compatibility and a negative cross-match. Bladder drainage via pancreaticoduodenocystostomy was performed in all of the patients. Due to a pulmonary embolus 1 patient (4.3%) died at 2 months. The actuarial patient survival rates at 3 months and 1, 3, and 5 years were 95.6%. Causes for the renal graft loss were chronic allograft nephropathy in 3 cases (13%) and death of the patient in 1 case (4.3%). The actuarial censored renal allograft survival rates at 3 months and at 1 year were 100%, and at 3 and 5 years were 91.3%. Causes for the renal graft loss were chronic rejection in 1 case (4.3%) and patient death in 1 case (4.3%). The actuarial censored pancreatic allograft survival rates at 3 months and at 1 and 3 years were 100%, and at 5 years was 95.6%. The results of this work add further evidence that SPK is the gold standard therapy for selected patients with end-stage CKD due to DM 1.

An abstract of the research paper "Use of elder donors for cadaveric single kidney transplantation: a new evolution or an inacceptable risk?," presented at the 13th annual meeting of the Italian Society of Geriatric Surgery, held in Lecce, Italy during December 2-4, 2010, is presented.

Abstract: Validity of living donor kidney transplantation is universally accepted. In contrast, after enthusiastic adoption in the 1990s, living donor liver transplantation has decreased in recent years. The aim of the present study was to evaluate retrospectively the current use of this form of donation in Italy by comparing liver and kidney cadaveric and living donations from 2002 to 2010. The number of liver transplantations from living donors has decreased from 34 in 2002 (3.9% of total) to 13 in 2010 (1.3% of total). In contrast, kidney transplantation from living donors increased from 126 (7.9% of total) to 186 (11% of total). We observed that living donations for kidney transplantation are still underused, especially with unrelated donors. Living donor liver transplantation has decreased in recent years; this procedure should be reserved to centers with particular expertise. It would be appropriate to implement programs to increase the attention of health professionals and the general population and to integrate living donations into programs of deceased organ donation. [Copyright &y& Elsevier]