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A meeting entitled Renal BIopsy for Kidney Transplantation Therapy (ReBIrth) took place on May 31 st , 2022 in Bologna, Italy. The meeting drew together nephrologists, surgeons, and pathologists and recognized as experts in the field of kidney transplantation in Italy. In this paper, we present our experience working with kidney transplants in the current era of immunosuppression therapy. The primary aim is to report the histopathological characteristics of failed kidney allografts after a consensus of experts reviewed the cases on a wholeslide imaging digital platform. Regardless of the cases discussed, digital pathology was reliable in identifying all the morphological and immunohistochemical features required to improve the correct use of immunosuppressive therapy to prevent graft failure and optimize patient management., (Copyright © 2023 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

De novo tumors in renal allograft recipients are a severe complication during long-term follow-up after transplantation and may require transplantectomy. Herein we present a case of de novo renal tumor arising in the renal allograft, treated with the less invasive image-guided radiofrequency ablation (RFA) with long-term follow-up. A tumor was detected during the routine annual follow-up in a patient with good renal function who underwent renal transplantation in 1989. Computed tomography (CT) showed a mass in the allograft whose shape, vascularization, and density suggested the presence of a solid, malignant mass, located in the upper renal pole, that measured 17 mm. CT-guided RFA was performed successfully, and the outcome was verified by an immediate control CT after the intervention. No residual pathologic tissue, major bleeding, or damage to the adjacent parenchyma was evidenced. The patient was discharged with stable renal function. CT scan and ultrasound were performed 3, 6, 12, 18, 24, and 36 months after RFA. No signs of change in renal function, recurrence, neovascularization, or damage to the adjacent microcirculation were observed during the 3-year follow-up. In conclusion, percutaneous RFA of small renal tumors occurring in renal allografts can be considered a function-sparing, safe, and effective therapeutic option when difficult surgical removal may be anticipated. Our experience also supports the need for yearly renal allograft ultrasound follow-up for early identification of small neoplasm than can be treated less invasively., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Delayed graft function is a frequent complication in deceased-donor kidney transplant, with an incidence ranging from 10% to 50% among different centers; it is also associated with lower graft survival. In this study, we aimed to identify risk factors for delayed graft function, particularly those associated with perioperative management (including cold ischemia time) and nonmodifiable recipient- and donor-related factors. The effects of delayed graft function on graft and patient outcomes were also evaluated., Materials and Methods: Our retrospective analyses included 125 adult patients who underwent deceased-donor kidney transplant. Delayed graft function was diagnosed if at least 1 dialysis treatment was required during the first week posttransplant according to Perico's definition., Results: Prevalence of delayed graft function was 30.4% (n = 38). Cold ischemia time was significantly prolonged in patients with delayed graft function compared with those without it. Multivariate regression showed that cold ischemia time was the only predictor of delayed graft function. A cutoff of 9 hours and 12 minutes was found as a limit beyond which delayed graft function occurred (sensitivity = 90%; specificity = 29%; area under the curve = 0.68). Greater donor and recipient age and longer pretransplant dialysis time in recipients were associated with occurrence of delayed graft function. In patients with delayed graft function, hospital stay duration was significantly greater and 1-year graft survival was significantly lower., Conclusions: Efforts should be focused on limiting cold ischemia time and associated injury to reduce occurrence of delayed graft function and consequently improve long-term graft survival in kidney transplant recipients. Optimization of posttransplant renal function with the help of new technologies, such as pulsatile perfusion, could be crucial for minimization of cold ischemia time.

Neoplasms occurring in renal grafts represent a relatively novel and rare condition, whose treatment has not been standardized yet. Radiofrequency thermal ablation (RFA) of renal graft neoplasms is a nephron-sparing treatment, reported to be safe and effective. However, even in the RFA field, there is no procedural standardization. In this review of the literature, mostly composed by case reports and case series, we aim to assess efficacy and complication rates of RFA in the treatment of kidney graft neoplasms, and summarize the various procedural protocols found in the literature, using an easy-to-read point format. We performed a literature search in PubMed/MEDLINE with an overall description of 66 renal graft lesion treated with RFA, with a mean follow-up of 16.3 months (range 3-54.3). Technical success was achieved in all cases, with only one recurrence reported (1/66; 1.5%), occurring at 6-months follow-up. Complications occurred in 11 (11/66; 16.7%) patients. Based on literature review, RFA of renal graft neoplasms seems to be a feasible, safe, and effective treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Recurrent glomerulonephritis can negatively affect kidney allograft survival. However, how primary renal disease affects transplant outcomes in the new era of immunosuppression remains unclear., Materials and Methods: We categorized 426 kidney transplant recipients (performed from 1996 to 2007) into 4 disease groups: (1) 99 recipients with biopsy-proven immunologically mediated kidney disease, (2) 40 recipients with urologic disease, (3) 67 recipients with polycystic kidney disease, and (4) 220 recipients with other causes of terminal renal failure/uncertain kidney disease. Long-term transplant outcomes were compared between groups at 1, 5, and 10 years of follow-up., Results: Compared with the urologic, polycystic, and other diseases groups, the immunologic group showed significantly lower time of graft survival (9.5 ± 4 vs 8 ± 4 vs 8.5 ± 4 vs 7 ± 4 years, respectively) and estimated glomerular filtration rate (52.5 ± 32 vs 49 ± 22 vs 50 ± 32 vs 35.5 ± 30 mL/min; P < .05). Relative risk of 10-year graft loss for the immunologic group was 2.8 (95% confidence interval, 1.6-4.9). Recurrence rate was 12% in the immunologic group versus 1% and 0% in the other diseases and remaining groups (P < .05). The relative risk of 10-year graft loss for patients with recurrence was 2.7 (95% confidence interval, 1.2-6.3). Ten-year graft loss rates for patients with biopsy-proven acute rejection, chronic allograft nephropathy, and recurrent glomerulonephritis were 30%, 23%, and 42% (P < .05). For those with biopsy-proven recurrent glomerulonephritis, 10-year estimated glomerular filtration rate was significantly lower than for those with biopsy-proven acute rejection or chronic allograft nephropathy (14 ± 6 vs 18 ± 7 vs 30 ± 10 mL/min; P < .05)., Conclusions: Kidney transplant recipients with immunologically mediated kidney diseases have inferior long-term allograft survival and function versus patients with other causes of renal failure. Recurrence represents the strongest risk factor for premature loss of function and transplant failure.

Background: Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process., Methods: Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome., Results: HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05)., Conclusions: Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Cytomegalovirus (CMV) disease represents a major cause of post-transplantation morbidity and mortality. To estimate the risk of infection and monitor response to antiviral therapy, current guidelines suggest combination of viral load monitoring with direct assessment of CMV-specific immune response. We used enzyme-linked immunospot (ELISpot) for the evaluation of CMV-specific T-cell response in kidney transplant recipients with CMV viremia and investigated how information gained could help manage CMV infection., Methods: Seventeen patients on pre-emptive antiviral therapy and CMV quantitative polymerase chain reaction (qPCR) ≥500 copies/mL (first episode after transplantation) were assessed using ELISpot and divided into Weak (9 patients with baseline ELISpot <25 spot-forming colonies [SFCs]/200,000 peripheral blood mononuclear cells [PBMCs]) and Strong Responders (8 patients with baseline ELISpot ≥25 SFCs/200,000 PBMCs). CMV-specific T-cell response, infection severity, viral load, and antiviral therapy were prospectively recorded and compared between groups at 1, 2, and 24 months of follow-up., Results: Demographic and transplant characteristics of Weak and Strong Responders were similar. No episodes of CMV disease were observed. Weak Responders were more likely to experience CMV syndrome (56% vs 36.5%) and late virus reactivation (56% vs 25%) than Strong Responders. Weak Responders showed higher baseline median viral loads (19,700 vs 9265 copies/mL) and needed antiviral therapy for longer (179 vs 59.5 days). T-cell response showed 2 main patterns: early and delayed., Conclusions: ELISpot provides prognostic information about infection severity, risk of late reactivation, and response to therapy. Randomized trials, evaluating the need for antiviral therapy in kidney transplant recipients with asymptomatic infection and effective virus-specific T-cell immune response, are warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: To safely expand our living donor pool, we recently decided to work on 3 areas: analysis of causes of exclusion of potential donors, the results of which we recently published, introduction of laparoscopic donor nephrectomy (LDN), and ABO-incompatible (ABOi) transplantation. We sought to determine the impact of the new strategy on living donor recruitment and transplantation during over a 10-year period at a single institution., Methods: From January 2005 to September 2014, we evaluated 131 living donors. Of these, 80 (61%) were genetically related, 51 (39%) unrelated, 119 (91%) ABO compatible (ABOc), 12 ABOi (9%). The analysis was divided into 2 eras: era 1, 2005-2010 (n = 53) included the use of open lumbotomy and acceptance of ABOc only; and era 2, 2011-2014 (n = 78), which saw the introduction of LDN and ABOi transplantation., Results: Forty-five (34%) potential candidates successfully donated, 67 (51%) were excluded, and 19 (15%) were actively undergoing evaluation. Overall, 53 potential donors were evaluated in era 1 (8.8 donors/year), 78 in era 2 (19.5 donors/year). There were fewer excluded donors in era 2 vs era 1 (62% era 1 vs 44% era 2), and living donor kidney transplantation (LDKT) significantly increased in era 2 vs era 1 (3.3/year era 1 vs 7.1/year era 2). The establishment of an ABOi LDKT program led to a 15% increase of evaluations in era 2 (12/78 donors)., Conclusions: LDN along with ABOi LDKT allowed for an improvement in recruitment of living donors and corresponding LDKT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: Aim of this study was to evaluate the association between attachment style, compliance, quality of life and renal function in adult patients after kidney transplantation., Methods: A total of 43 adult patients who received a kidney transplant more than 3 months before were enrolled and were asked to complete two Self-Report questionnaires: Attachment Style Questionnaire (ASQ-40) and Short Form Health Survey (SF-36). Also compliance was measured using appropriate questions., Results: Linear regression analysis showed associations between the confidence in relationships (ASQ-40) and compliance [beta = -0.37; B = -0.02; t(41) = -2.51; p = 0.02]; aspects of anxious attachment style (ASQ-40) and creatinine levels [beta = 0.3; B = 0.13; t(41) = 2.03; p = 0.04]; aspects of avoidant attachment style (ASQ-40) and compliance [beta = -0.37; B = -3.15; t(41) = -2.35; p = 0.02]. Patients who exhibited avoidant attachment had a significantly better perception of their own general health than patients with anxious [F(2,37) = 6.8; p < 0.05] or secure attachment; however, they had a worse perception regarding role limitations due to emotional problems, compared to patients with anxious attachment [F(2,37) = 6.4; p < 0.05]., Discussion: The results of this study suggest that the evaluation of the attachment style in adult kidney transplant patients can contribute to plan a goal-directed psychological support program for these patients, in order to increase their compliance. The association between aspects of anxious attachment style and creatinine level needs more investigations.

Unlabelled: Recent studies show that alexithymia may influence compliance and quality of life in different clinical situations. The aim of this study was to evaluate the associations between alexithymia or emotional self-efficacy and compliance, quality of life (QoL) and renal function in renal transplant patients., Methods: Forty-three patients were enrolled during a follow-up visit (>3 months post-transplant) and were asked to complete three self-report questionnaires (TAS-20, SF-36, RESE) to answer the following items: "In the past four weeks, how many times did you fail to take your prescribed dose?" and "How would you rate your adherence levels from 0 to 100?" (visual analogue scale)., Results: Alexithymia was positively correlated with non-compliance (r=.314; p=.04), and negatively with QoL dimensions. Analysis of variance confirmed that patients with high levels of alexithymia reported a negative perception of their QoL (mental health: F(1,41)=7,6; p=.008) and lower levels of compliance (F(1,41)=12,5; p=.001) compared with patients with low levels of alexithymia. The self-efficacy in the management of negative emotions was significantly correlated (r=-.314; p=.04) with creatinine levels and positively with the QoL (mental health: r=.421; p=.005)., Discussion: The inability to recognize and express emotions, as well as the ability to manage negative emotions, may influence compliance and QoL of renal transplant patients. Focused psychological support could be useful in these patients in order to increase their compliance and QoL., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: There is no consensus on the optimal perioperative antibiotic prophylaxis regimen for renal transplant recipients. Some studies have reported that irrigation of the wound at the time of closure without systemic antibiotics may suffice to minimize the risk for surgical site infection (SSI), but many centers still use long-term, multidose regimens in which antibiotics are administered until removal of foreign bodies occur, such as the urethral catheter, drain and central line., Methods: We designed a prospective, randomized, multicenter, controlled trial to compare a single dose versus a multidose regimen of systemic antibiotic prophylaxis in adult, nondiabetic, non-morbidly obese patients undergoing renal transplantation. The primary endpoint was the incidence of SSI; the assessment of other infection in the first postoperative month was the secondary endpoint., Results: Two hundred five patients were enrolled and randomized to receive either a single (n = 103) or multidose antibiotic regimen (n = 102) for prophylaxis. The incidences of SSI and urinary tract infection were similar in both groups., Conclusion: As the dramatic increase in antibiotic resistance has mandated the implementation of global programs to optimize the use of antibiotic agents in humans, we believe that the single dose regimen is preferred, at least in nondiabetic, non-morbidly obese, adult renal transplant recipients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The complexity of treatment after solid organ transplantation has been related to non-adherence to therapy prescriptions and to reduced graft survival. The aim of this study was to evaluate the middle-term effects of the conversion from Prograf (TAC), to extended-release tacrolimus (Advagraf) (ADV) in stable kidney transplant recipients., Methods: Conversion from TAC to ADV (dose, 1:1 mg/mg) was planned in 78 kidney transplant patients with stable renal function 71±48 months after renal transplantation. Before conversion, 1 week after conversion, and every 6 months up to 3 years, patients were evaluated clinically and by means of the usual blood chemistry and pharmacologic parameters., Results: Twenty patients (26%) refused to change their pre-existing immunosuppressive therapy; therefore, 58 patients entered the study and 45 (77%) completed the 3-year follow-up. Patient survival was 98% and allograft survival was 96%. Significant reduction in serum creatinine levels and increased glomerular filtration rate were observed after conversion (3-year creatinine: before TAC 1.67±0.47 mg/dL vs after ADV 1.47±0.62 mg/dL, P<.001; glomerular filtration rate, MDRD abbreviated: before TAC 49±15 mL/min vs after ADV 59±24 mL/min, P<.001). The daily dose and C0 blood levels of tacrolimus were stable before and after conversion (dose before vs 3 years after conversion: TAC 3.79±1.81 mg/day vs ADV 3.54±1.86 mg/day, P=ns; C0 tacrolimus blood levels, before vs 3 years after conversion: TAC 6.03±1.75 ng/mL vs ADV: 5.58±1.38 ng/mL, P = NS). One patient in the ADV group had an episode of acute rejection (2%)., Conclusions: Our data support the safety and efficacy of converting from Prograf to Advagraf in stable kidney transplant patients in the middle term. We suggest that the observed improvement in renal function after conversion to ADV is related to the reduction of the 24-hour tacrolimus area under the curve exposure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Safety in conducting a clinical trial is a prerequisite for patients who will be enrolled into that study. The aim of the present study was to evaluate retrospectively if patient and graft survival were similar among patients who participated in clinical trials versus those who did not., Patients and Methods: We evaluated pretransplant and posttransplant characteristics of 245 kidney transplant (KT) patients who were selected to participate in at least one Phase II/Phase III clinical trial. We compared them with 361 KT patients who were not enrolled or refused to participate in those clinical trials; all studies were conducted at a single transplant center. Inclusion/exclusion criteria were as noted for each individual protocol. Only studies with enrollment at time of graft implant were considered., Results: Selection of patients participating in clinical trials in general exclude high-risk patients. In our experience, only 36% of transplanted patients were selected for a multicenter, prospective, randomized, international study that included changes to the strategies in the administration of immunosuppressive drugs already on the market or development of a new immunosuppressant. After 5 years, graft and patient survival rates were similar between those who participated and those who did not participate in a clinical study. Although our data were collected retrospectively, an alternative design to achieve these conclusions would be a noninferiority study., Conclusions: Our results demonstrated similar rates of graft and patient survival among enrolled patients versus nonenrolled patients. Outcome surveillance offers safety in participating in clinical trials that involve changes in standard immunosuppression therapy and are part of the research necessary to develop patient-centered medical interventions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Encapsulating peritoneal sclerosis is a serious complication of peritoneal dialysis and can occur even after transplant. The gut is partially or totally enveloped by a thick fibrous membrane that leads to the formation of multiple sections containing intestinal loops contracted and reduced in volume. Exacerbation after renal transplantation is a very rare but sometimes dramatic condition. We report a patient who developed intestinal obstruction due to encapsulating peritoneal sclerosis 1 year after a deceased-donor kidney transplant. Treatment included laparotomy, small-bowel lengthening by release of adhesions, and high doses of corticosteroids. The patient received immunosuppressive therapy with a combination of low-dose cyclosporine, everolimus, and prednisone, unchanged except for a temporary steroid increase in the postoperative period. We report success with this combined surgical plus medical therapy, with no recurrence after 81 months of follow-up., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The evaluation of a potential living kidney donor (LKD) leads to exclusion of at least 50% of candidates. The aim of this study was to analyze the reasons for exclusion of potential LKDs referred to our center., Methods: We retrospectively analyzed historic and clinical data of all potential LKDs who were evaluated over 7 years from January 2005 to March 2012. Data were obtained by review of an electronic database., Results: Among 79 (50 female, 29 male) candidates, 24 (30.3%) successfully donated, comprising 22 related and 2 unrelated donors. We excluded 45 (56.9%), and 10 (12.6%) are actively undergoing evaluation. Reasons for exclusion were medical (n = 14; 31%), nonmedical (n = 18; 40%), positive cross-match (n = l7.7%), pregnancy (n = 2; 4.4%), and other reasons (n = 3; 6.6%). Of the 14 donors excluded for medical reasons, 75.8% were due to diabetes, cardiovascular disease, hypertension, or obesity and 21.5% to inadequate renal function, malignancy, or liver disease. Of the 18 (40%) excluded for nonmedical reasons, 6 (33.3%) were because the intended recipient received a deceased-donor transplantation before the evaluation could be completed, 5 (27.7%) because the recipient was no longer a candidate for transplantation, 5 (27.7%) because of donor withdrawal, and 2 (11.1%) for other reasons., Conclusions: Positive cross-match and deceased-donor transplantation during the evaluation process were the 2 most common reasons for LKD exclusion. Evaluation of potential LKDs is time consuming, requiring a remarkable amount of human and material resources. A dedicated pathway for the diagnostic work-up of LKDs may speed- the evaluation process and improve its efficiency, use of ABO-incompatible or paired-exchange donations may increase the yield of donor organs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Psoriasis, one of the most common immune-mediated inflammatory diseases of the skin is mediated by activated effector T cells., Case Report: We report a case of a 56-year-old white man with a 22-year history of severe psoriasis vulgaris with plaque and joint involvement, who experienced a complete clinical remission after renal transplantation. The patient had been on hemodialysis for 6 years because of chronic renal failure caused by an undetermined chronic nephropathy. Psoriasis, which worsened over the years, was symmetrically distributed as erythematous scaly plaques that had increased until they covered about 50% of the body surface, involving mainly the abdomen, legs, back, and arms. The patient also complained of severe itching an responsive to drugs. He had been treated with topical and systemic corticosteroids and phototherapy several times without benefit. After renal transplantation he underwent immunosuppressive therapy with corticosteroids, mycophenolate mofetil (MMF), and tacrolimus (Advagraf, beginning starting dose 1 mg/kg/day, C0 10 ng/mL)., Results: From the early days post-surgery the patient reported a fast improvement in the itching with progressive reduction of the skin lesions. After 4 months follow-up the psoriasis had completely regressed, presumably due to the immunosuppressive regimen., Conclusion: This finding suggests that systemic immunosuppressive drugs may be useful for psoriasis an responsive to conventional therapy., (Copyright © 2013. Published by Elsevier Inc.)

Background: Cardiovascular (CV) disease is the first cause of death after kidney transplantation. Left ventricular hypertrophy (LVH) is one of the main CV risk factors. It has been reported that the antiproliferative properties of everolimus (EVE) treatment may decrease left ventricular mass. The aim of this study was to evaluate the evolution of LVH in two groups of kidney transplant recipients receiving immunosuppressive treatment with low-dose calcineurin inhibitor (CNI) + EVE or CNI + mycophenolate mofetil (MMF)., Methods: We evaluated 104 patients of mean age 47.5 ± 13.1 years who underwent kidney transplantation between January 2006 and December 2009 pretransplant by echocardiography, which was repeated every year for 3 years during which all patients continued the initial therapy. Over the 3-year period 76 subjects were treated with MMF, and 28 with EVE. We recorded left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness in diastole (IVSTD), left ventricular posterior wall thickness in diastole (LVPWD), left ventricular end-diastolic volume and end-systolic volume during the follow-up echocardiographic evaluations., Results: No differences in the evolution of the echocardiographic parameters were observed between the two groups-MMF versus EVE group: LVEDD, 50.3 ± 5.1 versus 51.2 ± 6.7 mm; IVSTD, 11.2 ± 1.9 versus 11.3 ± 2 mm; LVPWD, 10.2 ± 1.9 versus 10.5 ± 1.7 mm; relative wall thickness, 0.041 ± 0.08 versus 0.42 ± 0.08; ejection fraction, 63 ± 6% versus 61 ± 5%; and left ventricular mass index, 113 ± 28.9 versus 121.9 ± 39.4 g/m(2), respectively. Compared with pretransplant echocardiographic evaluations, similar reductions in left ventricular mass index were noted in both groups after transplantation., Conclusions: We observed that after renal transplantation there was a reduction of the LVH respect to the pretransplant dialytic status. The two immunosuppressive regimen did not influence the evolution of post-transplant LVH., (Copyright © 2013. Published by Elsevier Inc.)

We compared in kidney transplantation two immunosuppressive regimens: tacrolimus plus mycophenolate mofetil (MMF) (TAC) and everolimus plus low-dose cyclosporine (EVE). Sixty consecutive patients received TAC (30 patients) or EVE (30 patients) as immunosuppressive regimen; all subjects also received induction with basiliximab and corticosteroids. After three-yr follow-up, no difference was found in patient and graft survival (PTS: TAC: 97% vs. EVE: 100%; GS: TAC: 93% vs. EVE: 93%). The incidence of acute rejection was higher in the EVE group but the difference was not statistically significant (17% vs. 23%, p = ns). Patients in EVE showed higher serum cholesterol (205 ± 41 vs. 235 ± 41 mg/dL, p = 0.0012) and lower hemoglobin concentration (13.6 ± 1.4 vs. 12.4 ± 1.9, p = 0.01). Renal function was not significantly different in the two groups (3 Y creatinine: TAC 1.4 ± 0.8 vs. EVE 1.6 ± 0.8 mg/dL, p = ns). Treatment discontinuation was higher in the EVE group (TAC 17 vs. EVE 36%, p = ns). Our data show that in the middle-term follow-up, an immunosuppressive regimen with tacrolimus plus MMF has a similar efficacy and safety profile in comparison with the combination of low-exposure cyclosporine plus everolimus. Further follow up could evidence the benefits related to the anti-proliferative effects of everolimus., (© 2013 John Wiley & Sons A/S.)

Background: The effectiveness of restrictive procedures has been inferior to that of malabsorbitive ones. Recent variants of restrictive procedures, i.e., gastric banding and sleeve gastrectomy, confirm the strive for more efficacious solutions with less complications. We investigated the balance between effectiveness and complications for a new restrictive procedure, a Transoral Endoscopic Vertical Gastroplasty (TOGa®), Methods: Seventy-nine morbidly obese patients were submitted to one out of three surgical procedures: TOGa® (29 patients), laparoscopic gastric bypass (LRYGBP; 20 patients), and biliopancreatic diversion (BPD; 30 patients). Mean BMI were 41.7 (35.4-46.6), 44.8 (36.4-54), and 47.5 (41-60.3), respectively. All the patients reached a 2-year follow-up., Results: In TOGa® group BMI, respectively at 12 and 24 months, was 34.5 and 35.5, with 44 and 48.3% of patients with BMI lower than 35. In LRYGBP group, BMI was 30.7 and 29.2 kg/m(2), with 80 and 85% of patients with BMI < 35. In BPD group, BMI was 30 and 29.6 kg/m(2), with 100 and 93.3% of patients with BMI < 35. In TOGa® group, 59% of patients with an initial BMI < 45 reached a BMI < 35, in comparison to 48% recorded in the whole group and to 14.3% in patients with initial BMI ≥ 45., Conclusions: In selected patients, TOGa®, was associated with good results after two years in terms of weight loss, even in comparison with LRYGBP and BPD. Minimal trauma, absence of complications, and short hospital stay justify this procedure for patients with low BMI.

Introduction: Metabolic syndrome (MS) is an important cardiovascular risk factor. The aim of this study was to evaluate the incidence of MS in an Italian kidney transplant recipient population and its relationship to the incidence of major adverse cardiovascular events (MACE) after renal transplantation., Methods: The prevalence of MS was evaluated according to the National Cholesterol Education Program Adult Treatment Panel III criteria among adult recipients who underwent a renal transplant between January 1997 and December 2007. In this period, we prospectively recorded the incidence of MACE to be related to the presence of MS., Results: We included 425 kidney transplant recipients in the study including 62% males and an overall median age 46 years (interquartile range=36-54). The prevalence of MS was 41.2% at 6 months after transplantation and 46.6% at 5 years. During the follow-up (median=5.1 years), 32 patients (7.5%) experienced at least one MACE. The detection of MS at 6 months after transplantation was significantly associated with an increased risk of MACE occurrence (MS IRR=2.2 P=.05)., Conclusions: Our findings indicated that MS was largely present in the transplant population confirming that as in the general population, it was a significant risk factor for the occurrence of severe cardiovascular disease. Early identification and treatment of patients with MS may improve long-term patient survival., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: The half-life of everolimus is approximately 28 hours, but everolimus is generally administered twice a day. The aim of this prospective, single-center, exploratory study was to compare the efficacy and safety of a once a day everolimus (OD) with the standard twice a day administration regimen (BID) as immunosuppressive therapy in renal transplantation., Methods: Forty-one de novo renal transplant recipients prospectively assigned to OD (n=21) or BID (n=20) treatment were followed for 1 year. In the OD group, everolimus was orally administered targeting a trough blood level of 2 to 5 ng/mL. In the BID group, everolimus was given twice a day targeting a trough blood level of 3 to 12 ng/mL. All patients also received induction with basiliximab and low-dose calcineurin inhibitor immunosuppression., Results: At 1 year follow-up patient and graft survivals were 100%. The intention-to-treat analysis showed similar renal function between the two regimens: serum creatinine values for OD 1.54 ± 0.6 versus BID 1.48 ± 0.53 mg/dL (P=NS). Also the occurrence of acute rejection episodes was not significantly different: 4.8% in the OD versus 15% in the BID group, (P=NS). The median trough blood levels were significantly lower among the OD group: OD 4.5 versus BID 7.2 ng/mL (P<.001)., Discussion: This study demonstrated that once a day administration of everolimus achieved excellent patient and graft survival and good renal function without an increased incidence of acute rejection episodes., (Copyright © 2011. Published by Elsevier Inc.)

Introduction: The extremely good results of renal transplantation have favored the use of pre-emptive procedures for treatment of patients with end-stage renal disease before entering dialysis, but still some concerns exist about patient survival. The aim of this study was to analyze the evolution of death rates and the causes of mortality among recipients of procedures performed between 1970 and 2007., Methods: We examined the outcomes at 1, 5, 10, and 15 years follow-up of 793 adults who underwent primary or repeat renal transplantation from living or deceased donors between January 1, 1970 and December 31, 2007. To evaluate the impact of immunosuppressive regimens on patient survivals, we considered 3 time intervals: the precyclosporine era, the cyclosporine era, and the postcyclosporine era., Results: During follow-up 115/793 (14.5%) renal transplant recipients died. There was a significant decrease in the overall mortality rate over the years. Patients who underwent transplantation more recently in the postcyclosporine era (1997-2007) showed a mortality rate of 1.8% (7/394) at 1 year and 3.3% (13/394) at 5 years, significantly lower than in previous periods. There was no significant change in the most frequent causes of death: cardiovascular diseases and sepsis., Conclusion: Our data indicated a significant improvement in patient survival after renal transplantation over the last decade. These data are significantly better than those reported for dialysis treatment thus supporting the strategy of pre-emptive transplantation for end-stage renal disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Improvements in immunosuppressive therapy have significantly changed results of organ transplantation. The aim of this study was to review the causes of mortality among our renal transplant population., Methods: This study population included 750 patients who underwent kidney transplantation between 1970 and 2007. During the follow-up, we recorded all causes of death and major cardiovascular events: stroke, myocardial infarction, angina pectoris, and cardiac death were considered major adverse cardiovascular events (MACE) The occurrence of MACE was related to wellestablished cardiovascular risk factors-age, sex, arterial blood pressure, diabetes, renal function, cardiovascular body mass index, history, or dyslipidemia measured at 6 months, as well as 5 and 10 years after transplantation. At these times we also calculated the INDANA, Framingham, and ltalian Heart Project scores., Results: The median follow-up was 63 months and mean age was 45 +/- 11 years. The median waiting time for transplant was 34 months. During follow up, 22 patients (6.1%) developed MACE, with 2 (0.55%) events within 6 months 10 (3.1%) between 6 months and 5 years, and 10 (6.5%) between 5 and 10 years. The INDANA score at all the time periods was significantly different among patients with vs without MACE (P < .0001), whereas no significant difference was observed using the Framinghan or the Italian Heart Project scores (P < .11)., Conclusion: Our study indicated that the INDANA scoring system better predicted the risk of MACE as approved to the Framinghan or Italian Heart Project systems. The INDANA score might be used to plan selective cardiovascular screening among recipients., (Copyright (c) 2010. Published by Elsevier Inc.)

Introduction: The half-life of everolimus is approximately 28 hours, but everolimus is normally administered twice a day. The aim of this prospective, single-center, exploratory study was to compare the efficacy and safety of a once a day (OD) everolimus regimen versus the standard twice a day regimen (BID) for immunosuppressive therapy in renal transplantation., Methods: Forty de novo renal transplant recipients prospectively assigned to OD (n = 21) or BID (n = 19) were followed for 6 months. In the OD group, everolimus was given orally once a day to target a trough blood level of 2-6 ng/mL. In the BID, group everolimus was given twice a day to target a trough blood level of 3-12 ng/mL. All patients also received induction treatment with basiliximab and low-dose calcineurin inhibitors., Results: At 6 months follow-up, patient and graft survivals were 100%; renal function and acute rejection rates were similar between the 2 regimens. Patients in the OD group showed significantly lower cholesterol and triglyceride levels compared with those in the BID group, namely, total cholesterol level, OD 212 +/- 54 versus BID 249 +/- 59 mg/dL (P < .05), and serum triglycerides, OD 162 +/- 72 versus BID 245 +/- 133 mg/dL (P < .02)., Discussion: This study showed that OD administration of everolimus provided excellent patient and graft survivals and good renal function without an increased incidence of acute rejection episodes. The lipid profile was significantly better among patients receiving everolimus OD. These findings suggested that everolimus can be safely administered once a day., (Copyright (c) 2010. Published by Elsevier Inc.)

Old-for-old renal transplantation is becoming more frequent, but the optimal immunosuppressive regimens for this transplant population are still unclear. The aim of this pilot prospective study was to evaluate the efficacy and safety of the combination of basiliximab with a short course of low-dose thymoglobulin induction therapy among a group of patients receiving kidneys from donors >60 years (OLD), compared with those receiving organs from donors <60 years (YNG). Forty-six consecutive deceased donor kidney transplant patients received induction therapy with a combination of basiliximab (20 mg IV on days 0 and 4) and thymoglobulin (200 mg total dose IV on days 0-3). As maintenance immunosuppression starting on day 4, patients received a low dose of calcineurin inhibitor and steroids. Demographic characteristics at baseline were not significantly different between the 2 groups. At 6 months, patient survival, graft survival, and acute rejection rates were similar between the YNG and OLD groups: 100% and 95%, 96% and 95%, and 8% and 0%, respectively. Patients in the OLD group showed higher serum creatinine concentrations (YNG 1.5 +/- 0.3 vs OLD 1.9 +/- 0.3 mg/dL; P = .0002) but not proteinuria (YNG 0.11 +/- 0.11 vs OLD 0.15 +/- 0.14 g/24 h; P = ns). No significant difference was evident between the 2 groups regarding infectious, hematologic, or posttransplantation lymphoproliferative disorder complications. This study showed that a combination of basiliximab and a short course of low-dose thymoglobulin provided effective and safe immunosuppression, in old-for-old renal transplantation, with good renal function without an increased risk of posttransplantation infectious or hematologic complications., (Copyright (c) 2010. Published by Elsevier Inc.)

Objective: The aim of this prospective study was to compare the cardiovascular risk (CVR) profile in patients treated with 2 different immunosuppressive regimens: tacrolimus and mycophenolate mofetil (TAC) compared with everolimus and low-dose cyclosporine (EVL)., Patients and Methods: Sixty consecutive renal transplant recipients prospectively assigned to TAC (n = 30) or to EVL (n = 30) were followed for 6 months. TAC group immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil (MMF), and steroid. EVL group immunosuppression consisted of basiliximab, everolimus, and low doses of cyclosporine and steroid. Main CVR factors analyzed were: hypertension, dyslipidemia, posttransplant diabetes mellitus, and weight gain., Results: Six months posttransplantation, patients in the EVL group showed significantly higher mean serum cholesterol (P < .003) and serum triglyceride levels (P < .027), as well as a greater number of patients were receiving statin treatment (P < .05). Mean systolic blood pressure, mean diastolic blood pressure, number of patients treated for hypertension, number of antihypertensive medications prescribed per patient, posttransplant weight gain, and posttransplant diabetes mellitus were not significantly different among the EVL and TAC groups after 1, 3, and 6 months posttransplantation., Conclusions: This study showed that at 6 months posttransplantation, patients on EVL displayed significantly greater dyslipidemia with respect to the TAC group. A longer follow-up will be necessary to discover whether the presence of everolimus in the immunosuppressive regimen provides significant benefits for the CVR of renal transplant recipients.

Everolimus (EVL) has shown a potential to reduce nephrotoxicity associated with cyclosporine (CsA) while providing similar protection against rejection. We analyzed the incidence of acute rejection episodes (ARE) among 20 cadaveric renal transplant recipients treated with the combination of EVL + CsA. Immunosuppression consisted of basiliximab induction given pretransplant and on day 4 posttransplant; EVL at a starting dose of 1.5 mg/day followed by concentration control to trough levels of 3 to 8 ng/mL by day 7; CsA at a starting dose of 4 mg/kg per day and then concentration controlled with C2 monitoring (C2 500-700 ng/mL); and steroids in a tapering regimen to reach 5 mg by day 30. The overall incidence of ARE was 25%. On postoperative day 7, patients with ARE showed significantly lower mean EVL trough concentrations compared with those not experiencing ARE (NO ARE: 2.2 +/- 2.1 ng/mL vs 4.8 +/- 2.4 ng/mL) (P = .05). The CsA C2 values were close to the lower end of the target range on day 3 (583 +/- 334 ng/mL). All rejecting grafts were functioning at 3 months posttransplantations, but mean serum creatinine was higher in the ARE group (ARE 2.2 +/- 0.7 mg/dL vs 1.1 +/- 0.2 NO ARE; P = .04). In conclusion, whenever EVL is used in combination with CsA to protect kidney transplant patients against the risk of acute rejection, a threshold of 3 ng/mL must be reached in the first week posttransplantation. We suggest careful monitoring of EVL exposure and increased EVL starting doses.

Lymphocele is a complication of renal transplantation, representing a lymphatic collection around the grafted kidney. The use of the immunosuppressive agent sirolimus (SRL) has been associated with a significant increase in lymphocele formation. This complication has been related to the antiproliferative activity of SRL, which delays surgical wound repair and closure of injured lymphatic vessels. The aim of this study was to relate the incidence of lymphocele with immunosuppression among 158 renal transplant patients operated with routine closure of all the visible lymphatic vessels around the iliac vessels and at the renal hilum. The incidence of lymphocele was not significantly different among the various immunosuppressive regimens.

Sirolimus (SRL) in combination with Cyclosporine A (CsA) and steroids has been shown to lower the incidence of acute renal allograft rejection episodes, allowing CsA sparing. We retrospectively compared the incidence of posttransplant diabetes mellitus (PTDM) among kidney transplant recipients (KTx) immunosuppressed with SRL + CsA versus CsA alone. Patients were divided into two groups: SRL + CsA (n = 38) versus CsA (n = 48). Mean follow-up was 53.9 +/- 17.1 months. Seventeen/86 subjects (19.8%) developed diabetes after transplantation (7 IFG, 8.1%; 10 PTDM, 11.6%). The incidence was significantly higher in SRL + CsA (12/38 patients, 31.6%) compared with CsA (5/43 patients, 10.4%) (P = .0144, odds ratio 3.97). More patients required treatment in the SRL + CsA compared to CsA alone cohort (13.2% vs 2.1%, P = .051): 4 pts (10.5%) became insulin- dependent among SRL+CsA, vs none in the CsA group. Use of OHD was similar in both groups (2.6% SRL + CsA vs 2.1% CsA). There were no significant differences between the two groups in terms of age, sex distribution, BMI, or serum creatinine at 1 to 3 and 5 years from transplantation. All PTDM patients are alive at follow-up, while two grafts were lost due to chronic renal allograft dysfunction. Within the limits of a small retrospective study, we observed that SRL in combination with CsA increased the diabetogenic potential of CsA. A possible explanation of our findings is that higher CsA doses were used in the early experience with SRL + CsA; therefore the higher incidence of PTDM that we observed in the SRL + CsA combination may be a sign of toxicity. Careful monitoring of blood levels is mandatory in the SRL + CsA combination to avoid pleiotropic toxicity.