Cardiovascular Outcomes in De Novo Kidney Transplant Recipients Receiving Everolimus and Reduced Calcineurin Inhibitor or Standard Triple Therapy: 24-month Post Hoc Analysis From TRANSFORM Study.

Background: The comparative impact of everolimus (EVR)-based regimens versus standard of care (mycophenolic acid+standard calcineurin inhibitor [MPA+sCNI]) on cardiovascular outcomes in de novo kidney transplant recipients (KTRs) is poorly understood. The incidence of major adverse cardiac events (MACEs) in KTRs receiving EVR+reduced CNI (rCNI) or MPA+sCNI from the TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen study was evaluated.

Methods: The incidence of MACE was determined for all randomized patients receiving at least 1 dose of the study drug.

Variation in Post-Transplant Cancer Incidence among Italian Kidney Transplant Recipients over a 25-Year Period.

This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997-2004; 2005-2012; and 2013-2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. Poisson regression was used to assess trends.

Process control: simply a matter of efficiency or of survival and costs? A single-centre quality improvement project in living donor renal transplant.

Background: Rising incidence and prevalence of end-stage renal disease is a worldwide concern for sustainability of healthcare systems and societies. Living donor renal transplant [LDRT] provides highest health achievements and cost containment than any alternative form of renal replacement therapy. Nonetheless, about 25% of potential LDRTs are missed for causes directly related with inadequate timing in donor assessment.

Evaluation of Everolimus Activity against Using In Vitro Models of Infection.

Even though Everolimus has been investigated in a phase II randomized trial as a host-directed therapy (HDT) to treat tuberculosis (TB), an oncological patient treated with Everolimus for a neuroendocrine pancreatic neoplasia developed active TB twice and a non-tuberculous mycobacterial (NTM) infection in a year and a half time span. To investigate this interesting case, we isolated and genotypically characterized the () clinical strain from the patient and tested the effect of Everolimus on its viability in an axenic culture and in a peripheral blood mononuclear cell (PBMCs) infection model. To exclude strain-specific resistance, we tested the activity of Everolimus against strains of ancient and modern lineages.

Identification of the novel HLA-DPB1*1328:01 allele by next-generation sequencing.

The novel HLA-DPB1*1328:01 allele differs from HLA-DPB1*04:01:01:01 by one nucleotide substitution in exon 4.

Non-Immunologic Causes of Late Death-Censored Kidney Graft Failure: A Personalized Approach.

Despite continuous advances in surgical and immunosuppressive protocols, the long-term survival of transplanted kidneys is still far from being satisfactory. Antibody-mediated rejection, recurrent autoimmune diseases, and death with functioning graft are the most frequent causes of late-kidney allograft failure. However, in addition to these complications, a number of other non-immunologic events may impair the function of transplanted kidneys and directly or indirectly lead to their failure.

Telemedicine monitoring in the follow-up of kidney transplant recipients: consensus indications from an Italian panel of surgeons and nephrologists after the COVID-19 experience.

The quality of follow-up has clearly emerged as a key factor for long-term kidney graft survival. Currently, many clinics are facing difficulties in delivering optimal surveillance because of the increased number and complexity of kidney transplant recipients, and because of the COVID-19 pandemic. Additional ways of performing follow-up visits are needed and telemedicine has emerged as a tool to strengthen patient care intensity.

Application of the iBox prognostication system as a surrogate endpoint in the TRANSFORM randomised controlled trial: proof-of-concept study.

Objectives: Development of pharmaceutical agents in transplantation is currently limited by long waits for hard endpoints. We applied a validated integrative risk-prognostication system integrative Box (iBox) as a surrogate endpoint to the TRANSFORM Study, a large randomised controlled trial, to project individual patient long-term kidney allograft survival from 1 year to 11 years after randomisation.

Design: Post-hoc analysis of a randomised open-label controlled trial.

The impact of cancer on the risk of death with a functioning graft of Italian kidney transplant recipients.

This study assessed the impact of cancer on the risk of death with a functioning graft of kidney transplant (KT) recipients, as compared to corresponding recipients without cancer. A matched cohort study was conducted using data from a cohort of 13 245 individuals who had undergone KT in 17 Italian centers (1997-2017). Cases were defined as subjects diagnosed with any cancer after KT.

Image-Guided Thermal Ablation in De Novo Renal Tumor Arising in Kidney Allograft: 3-Year Follow-Up. A Case Report.

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.

Mycophenolate mofetil versus azathioprine in kidney transplant recipients on steroid-free, low-dose cyclosporine immunosuppression (ATHENA): A pragmatic randomized trial.

Background: We compared protection of mycophenolate mofetil (MMF) and azathioprine (AZA) against acute cellular rejection (ACR) and chronic allograft nephropathy (CAN) in kidney transplant recipients on steroid-free, low-dose cyclosporine (CsA) microemulsion maintenance immunosuppression.

Methods And Findings: ATHENA, a pragmatic, prospective, multicenter trial conducted by 6 Italian transplant centers, compared the outcomes of 233 consenting recipients of a first deceased donor kidney transplant induced with low-dose thymoglobulin and basiliximab and randomized to MMF (750 mg twice/day, n = 119) or AZA (75 to 125 mg/day, n = 114) added-on maintenance low-dose CsA microemulsion and 1-week steroid. In patients without acute clinical or subclinical rejections, CsA dose was progressively halved.

Pre-emptive live donor kidney transplantation-moving barriers to opportunities: An ethical, legal and psychological aspects of organ transplantation view.

Live donor kidney transplantation (LDKT) is the optimal treatment modality for end stage renal disease (ESRD), enhancing patient and graft survival. Pre-emptive LDKT, prior to requirement for renal replacement therapy (RRT), provides further advantages, due to uraemia and dialysis avoidance. There are a number of potential barriers and opportunities to promoting pre-emptive LDKT.

Legislative proposal in Italy to facilitate contacts between deceased organ donor families and transplant recipients.

Contacts between organ donors and recipients might be possible in the near future in Italy. As suggested by The Italian Committee of Bioethics "anonymity is requested by the Italian National Transplant Centre" before transplantation anonymity shall be strict in order to grant privacy, gratuity, justice, solidarity and benefits and avoids organ trafficking. Following a period that is ethically correct and justifiable, organ donor families and recipients can meet after signing a valid declaration of consent, expressed on a template valid for the whole country.

Wound healing adverse events in kidney transplant recipients receiving everolimus with reduced calcineurin inhibitor exposure or current standard-of-care: insights from the 24-month TRANSFORM study.

Objectives: In TRANSFORM, kidney transplant recipients received either everolimus in combination with reduced-exposure calcineurin inhibitor (EVR+rCNI) at standard EVR pre-dose concentrations of 3-8 ng/mL or mycophenolic acid plus standard-exposure CNI (MPA+sCNI). The authors analyzed the incidence of wound healing adverse events (WHAEs) over the 2-year study period 15.

Methods: Patients were randomized to either EVR+rCNI or MPA+sCNI, both combined with induction therapy and steroids 19.

Global Kidney Exchange: opportunity or exploitation? An ELPAT/ESOT appraisal.

This paper addresses ethical, legal, and psychosocial aspects of Global Kidney Exchange (GKE). Concerns have been raised that GKE violates the nonpayment principle, exploits donors in low- and middle-income countries, and detracts from the aim of self-sufficiency. We review the arguments for and against GKE.

Raising awareness of unspecified living kidney donation: an ELPAT view.

Background: Living donor kidney transplantation (LDKT) is the preferred treatment for patients with end-stage renal disease and unspecified living kidney donation is morally justified. Despite the excellent outcomes of LDKT, unspecified kidney donation (UKD) is limited to a minority of European countries due to legal constraints and moral objections. Consequently, there are significant variations in practice and approach between countries and the contribution of UKD is undervalued.

Living Kidney Donation in a Type 1 Dent's Disease Patient from His Mother.

Introduction: Dent's disease is a rare X-linked recessive disorder that manifests in childhood or early adulthood and can lead to end-stage renal disease (ESRD). It occurs in males, who are hemizygous. In patients who develop ESRD, a deceased donor kidney transplant cures the disease.

Evidence-based practice: Guidance for using everolimus in combination with low-exposure calcineurin inhibitors as initial immunosuppression in kidney transplant patients.

The mammalian target of rapamycin (mTOR) inhibitor, everolimus, in combination with reduced-exposure calcineurin inhibitor (CNI), has been demonstrated in clinical trials to have comparable efficacy in low-to-moderate immunological risk kidney transplant recipients to the Standard of Care, mycophenolic acid (MPA) in combination with standard-exposure CNI. Current treatment guidelines consider mTOR inhibitors to be a second-line therapy in the majority of cases; however, given that everolimus-based regimens are associated with a reduced rate of viral infections after transplantation, their wider use could have great benefits for kidney transplant patients. In this evidence-based practice guideline, we consider the de novo use of everolimus in kidney transplant recipients.

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies.

Cytomegalovirus (CMV) remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and solid organ transplantation (SOT) recipients. In view of the uncertainties on the assessment and prevention of CMV infection in both transplant procedures, three Italian scientific societies for HSCT and SOT and for Clinical Microbiology appointed a panel of experts to compose a framework of recommendations. Recommendations were derived from a comprehensive analysis of the scientific literature and from a multidisciplinary consensus conference process.

Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study.

TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen) was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard-exposure CNI. Consistent with previously reported 12-month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) <50 mL/min per 1.73 m was achieved at month 24 (47.

Everolimus in kidney transplant recipients at high cardiovascular risk: a narrative review.

Kidney transplant recipients (KTRs) are at increased risk of cardiovascular (CV) morbidity and mortality, and side effects induced by immunosuppressive therapy may be a major contributor to this risk, together with traditional CV risk factors. Many strategies have been considered in order to reduce CV risk in KTRs, such as steroid and/or calcineurin inhibitor (CNI) minimization, but current data are inconclusive. The introduction of mammalian target of rapamycin (mTOR) inhibitors, the cornerstone of CNI minimization, in the immunosuppressive protocol may reduce both the incidence and severity of CNI-associated side effects; however, whether this strategy has an impact on CV risk after kidney transplantation needs to be evaluated.

Increased cancer risk in patients undergoing dialysis: a population-based cohort study in North-Eastern Italy.

Background: In southern Europe, the risk of cancer in patients with end-stage kidney disease receiving dialysis has not been well quantified. The aim of this study was to assess the overall pattern of risk for de novo malignancies (DNMs) among dialysis patients in the Friuli Venezia Giulia region, north-eastern Italy.

Methods: A population-based cohort study among 3407 dialysis patients was conducted through a record linkage between local healthcare databases and the cancer registry (1998-2013).

Radiofrequency thermal ablation of renal graft neoplasms: A literature review.

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.

Perioperative-, Recipient-, and Donor-Related Factors Affecting Delayed Graft Function in Kidney Transplantation.

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.