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1.
Int J Cancer ; 154(5): 842-851, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37924271

ABSTRACT

Kidney transplant (KT) recipients are known to be at risk of developing several cancer types; however, cancer mortality in this population is underinvestigated. Our study aimed to assess the risk of cancer death among Italian KT recipients compared to the corresponding general population. A cohort study was conducted among 7373 individuals who underwent KT between 2003 and 2020 in 17 Italian centers. Date and cause of death were retrieved until 31 December 2020. Indirect standardization was used to estimate standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs). Cancer was the most common cause of death among the 7373 KT recipients, constituting 32.4% of all deaths. A 1.8-fold excess mortality (95% CI: 1.59-2.09) was observed for all cancers combined. Lymphomas (SMR = 6.17, 95% CI: 3.81-9.25), kidney cancer (SMR = 5.44, 95% CI: 2.97-8.88) and skin melanoma (SMR = 3.19, 95% CI: 1.03-6.98) showed the highest excess death risks. In addition, SMRs were increased about 1.6 to 3.0 times for cancers of lung, breast, bladder and other hematopoietic and lymphoid tissues. As compared to the general population, relative cancer mortality risk remained significantly elevated in all age groups though it decreased with increasing age. A linear temporal increase in SMR over time was documented for all cancers combined (P < .01). Our study documented significantly higher risks of cancer death in KT recipients than in the corresponding general population. Such results support further investigation into the prevention and early detection of cancer in KT recipients.


Subject(s)
Kidney Neoplasms , Kidney Transplantation , Lymphoma , Neoplasms , Humans , Cohort Studies , Kidney Transplantation/adverse effects , Lymphoma/epidemiology , Kidney Neoplasms/complications , Cause of Death , Italy/epidemiology
2.
Transpl Int ; 37: 12283, 2024.
Article in English | MEDLINE | ID: mdl-38699173

ABSTRACT

The KDIGO guideline for acute rejection treatment recommends use of corticosteroids and suggests using lymphocyte-depleting agents as second line treatment. Aim of the study was to determine the current practices of detection and treatment of TCMR of kidney allografts amongst European kidney transplant centres. An invitation was sent through ESOT/EKITA newsletters and through social media to transplant professionals in Europe for taking part in the survey. A total of 129 transplant professionals responded to the survey. There was equal representation of small and large sized transplant centres. The majority of centres treat borderline changes (BL) and TCMR (Grade IA-B, IIA-B) in indication biopsies and protocol biopsies with corticosteroids as first line treatment. Thymoglobulin is used mainly as second line treatment for TCMR Grade IA-B (80%) and TCMR IIA-B (85%). Treatment success is most often evaluated within one month of therapy. There were no differences observed between the large and small centres for the management of TCMR. This survey highlights the common practices and diversity in clinics for the management of TCMR in Europe. Testing new therapies for TCMR should be in comparison to the current standard of care in Europe. Better consensus on treatment success is crucial for robust study designs.


Subject(s)
Graft Rejection , Kidney Transplantation , Humans , Graft Rejection/diagnosis , Europe , Surveys and Questionnaires , T-Lymphocytes/immunology , Immunosuppressive Agents/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Biopsy , Antilymphocyte Serum/therapeutic use
3.
Transpl Int ; 37: 12475, 2024.
Article in English | MEDLINE | ID: mdl-38665475

ABSTRACT

An increasing number of sensitized patients awaiting transplantation face limited options, leading to fatalities during dialysis and higher costs. The absence of established evidence highlights the need for collaborative consensus. Donor-specific antibodies (DSA)-triggered antibody-mediated rejection (AMR) significantly contributes to kidney graft failure, especially in sensitized patients. The European Society for Organ Transplantation (ESOT) launched the ENGAGE initiative, categorizing sensitized candidates by AMR risk to improve patient care. A systematic review assessed induction and maintenance regimens as well as antibody removal strategies, with statements subjected to the Delphi methodology. A Likert-scale survey was distributed to 53 European experts (Nephrologists, Transplant surgeons and Immunologists) with experience in kidney transplant recipient care. A rate ≥75% with the same answer was considered consensus. Consensus was achieved in 95.3% of statements. While most recommendations aligned, two statements related to complement inhibitors for AMR prophylaxis lacked consensus. The ENGAGE consensus presents contemporary recommendations for desensitization and immunomodulation strategies, grounded in predefined risk categories. The adoption of tailored, patient-specific measures is anticipated to streamline the care of sensitized recipients undergoing renal allografts. While this approach holds the promise of enhancing transplant accessibility and fostering long-term success in transplantation outcomes, its efficacy will need to be assessed through dedicated studies.


Subject(s)
Consensus , Delphi Technique , Graft Rejection , Kidney Transplantation , Humans , Graft Rejection/prevention & control , Graft Rejection/immunology , Europe , Isoantibodies/immunology , Transplant Recipients
4.
Transpl Int ; 36: 11410, 2023.
Article in English | MEDLINE | ID: mdl-37470063

ABSTRACT

The ESOT TLJ 3.0. consensus conference brought together leading experts in transplantation to develop evidence-based guidance on the standardization and clinical utility of pre-implantation kidney biopsy in the assessment of grafts from Expanded Criteria Donors (ECD). Seven themes were selected and underwent in-depth analysis after formulation of PICO (patient/population, intervention, comparison, outcomes) questions. After literature search, the statements for each key question were produced, rated according the GRADE approach [Quality of evidence: High (A), Moderate (B), Low (C); Strength of Recommendation: Strong (1), Weak (2)]. The statements were subsequently presented in-person at the Prague kick-off meeting, discussed and voted. After two rounds of discussion and voting, all 7 statements reached an overall agreement of 100% on the following issues: needle core/wedge/punch technique representatively [B,1], frozen/paraffin embedded section reliability [B,2], experienced/non-experienced on-call renal pathologist reproducibility/accuracy of the histological report [A,1], glomerulosclerosis/other parameters reproducibility [C,2], digital pathology/light microscopy in the measurement of histological variables [A,1], special stainings/Haematoxylin and Eosin alone comparison [A,1], glomerulosclerosis reliability versus other histological parameters to predict the graft survival, graft function, primary non-function [B,1]. This methodology has allowed to reach a full consensus among European experts on important technical topics regarding pre-implantation biopsy in the ECD graft assessment.


Subject(s)
Kidney Transplantation , Organ Transplantation , Humans , Kidney Transplantation/methods , Reproducibility of Results , Kidney/pathology , Biopsy , Tissue Donors , Graft Survival
5.
Am J Transplant ; 22(2): 588-598, 2022 02.
Article in English | MEDLINE | ID: mdl-34464503

ABSTRACT

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. For each case, two controls matched by gender, age, and year at KT were randomly selected from cohort members who were cancer-free at the time of diagnosis of the index case. Overall, 292 (20.5%) deaths with a functioning graft were recorded among 1425 cases and 238 (8.4%) among 2850 controls. KT recipients with cancer had a greater risk of death with a functioning graft (hazard ratio, HR = 3.31) than their respective controls. This pattern was consistent over a broad range of cancer types, including non-Hodgkin lymphoma (HR = 33.09), lung (HR = 20.51), breast (HR = 8.80), colon-rectum (HR = 3.51), and kidney (HR = 2.38). The survival gap was observed throughout the entire follow-up period, though the effect was more marked within 1 year from cancer diagnosis. These results call for close posttransplant surveillance to detect cancers at earlier stages when treatments are more effective in improving survival.


Subject(s)
Kidney Failure, Chronic , Kidney Transplantation , Neoplasms , Cohort Studies , Graft Rejection/diagnosis , Graft Survival , Humans , Kidney Transplantation/adverse effects , Neoplasms/epidemiology , Neoplasms/etiology , Risk Factors , Transplant Recipients
6.
Am J Nephrol ; 53(1): 1-9, 2022.
Article in English | MEDLINE | ID: mdl-34937022

ABSTRACT

INTRODUCTION: Infectious events are one of the leading causes of death in kidney transplant recipients (KTRs). KTRs have reduced cardiorespiratory fitness (CRF), a predictor for infections in other populations. The aim of this study was to investigate whether CRF and muscle strength are prognostic markers for infectious events in KTRs. METHODS: In this retrospective cohort study, 155 KTRs underwent an incremental, maximal cardiopulmonary exercise test (CPET) 3 months after transplantation. CRF was analyzed with peak oxygen consumption (VO2 peak) while muscle strength with isometric handgrip (HG) test. Laboratory blood samples and drug therapy were collected. The median follow-up period was 54 (interquartile range 38-62) months. Cox regression analyses were performed to evaluate predictors of infectious events adjusting for potential confounders. RESULTS: During this study, severe infectious events occurred in 41 subjects (26.5%). 15.5% (n = 24) of patients had a severely reduced CRF, defined as a VO2 peak below the 5th percentile of the reference values reported for a matched healthy population. The hazard ratio for infectious events in this subgroup was 2.389 (95% CI = 1.188-4.801, p = 0.014), independently of gender, age, BMI, time on dialysis, hemoglobin concentration, eGFR, diabetes, and immunosuppressive regimen. On the contrary, no significant association of HG strength and infections was found. CONCLUSION: Therefore, low CRF may be considered as a modifiable predictor of severe infectious events in KTRs. A CPET should thus be recommended for cardiovascular screening, evaluation of CRF, and tailored exercise prescription to reduce the risk of infections and potentially improve long-term outcomes of transplantation.


Subject(s)
Kidney Transplantation , Exercise Test , Hand Strength , Humans , Kidney Transplantation/adverse effects , Physical Fitness , Prognosis , Retrospective Studies , Transplant Recipients
7.
Transpl Int ; 35: 10511, 2022.
Article in English | MEDLINE | ID: mdl-36033645

ABSTRACT

This guideline, from a European Society of Organ Transplantation (ESOT) working group, concerns the management of kidney transplant patients with HLA antibodies. Sensitization should be defined using a virtual parameter such as calculated Reaction Frequency (cRF), which assesses HLA antibodies derived from the actual organ donor population. Highly sensitized patients should be prioritized in kidney allocation schemes and linking allocation schemes may increase opportunities. The use of the ENGAGE 5 ((Bestard et al., Transpl Int, 2021, 34: 1005-1018) system and online calculators for assessing risk is recommended. The Eurotransplant Acceptable Mismatch program should be extended. If strategies for finding a compatible kidney are very unlikely to yield a transplant, desensitization may be considered and should be performed with plasma exchange or immunoadsorption, supplemented with IViG and/or anti-CD20 antibody. Newer therapies, such as imlifidase, may offer alternatives. Few studies compare HLA incompatible transplantation with remaining on the waiting list, and comparisons of morbidity or quality of life do not exist. Kidney paired exchange programs (KEP) should be more widely used and should include unspecified and deceased donors, as well as compatible living donor pairs. The use of a KEP is preferred to desensitization, but highly sensitized patients should not be left on a KEP list indefinitely if the option of a direct incompatible transplant exists.


Subject(s)
Kidney Transplantation , Antibodies , HLA Antigens , Histocompatibility Testing , Humans , Living Donors , Quality of Life , Waiting Lists
8.
Transpl Int ; 35: 10138, 2022.
Article in English | MEDLINE | ID: mdl-35669972

ABSTRACT

Different types of kidney transplantations are performed worldwide, including biologically diverse donor/recipient combinations, which entail distinct patient/graft outcomes. Thus, proper immunological and non-immunological risk stratification should be considered, especially for patients included in interventional randomized clinical trials. This paper was prepared by a working group within the European Society for Organ Transplantation, which submitted a Broad Scientific Advice request to the European Medicines Agency (EMA) relating to clinical trial endpoints in kidney transplantation. After collaborative interactions, the EMA sent its final response in December 2020, highlighting the following: 1) transplantations performed between human leukocyte antigen (HLA)-identical donors and recipients carry significantly lower immunological risk than those from HLA-mismatched donors; 2) for the same allogeneic molecular HLA mismatch load, kidney grafts from living donors carry significantly lower immunological risk because they are better preserved and therefore less immunogenic than grafts from deceased donors; 3) single-antigen bead testing is the gold standard to establish the repertoire of serological sensitization and is used to define the presence of a recipient's circulating donor-specific antibodies (HLA-DSA); 4) molecular HLA mismatch analysis should help to further improve organ allocation compatibility and stratify immunological risk for primary alloimmune activation, but without consensus regarding which algorithm and cut-off to use it is difficult to integrate information into clinical practice/study design; 5) further clinical validation of other immune assays, such as those measuring anti-donor cellular memory (T/B cell ELISpot assays) and non-HLA-DSA, is needed; 6) routine clinical tests that reliably measure innate immune alloreactivity are lacking.


Subject(s)
Kidney Transplantation , Graft Rejection , Graft Survival , HLA Antigens , Histocompatibility Testing , Humans , Living Donors , Risk Assessment , Tissue Donors
9.
Transpl Int ; 35: 10139, 2022.
Article in English | MEDLINE | ID: mdl-35669976

ABSTRACT

Clinical study endpoints that assess the efficacy of interventions in patients with chronic renal insufficiency can be adopted for use in kidney transplantation trials, given the pathophysiological similarities between both conditions. Kidney dysfunction is reflected in the glomerular filtration rate (GFR), and although a predefined (e.g., 50%) reduction in GFR was recommended as an endpoint by the European Medicines Agency (EMA) in 2016, many other endpoints are also included in clinical trials. End-stage renal disease is strongly associated with a change in estimated (e)GFR, and eGFR trajectories or slopes are increasingly used as endpoints in clinical intervention trials in chronic kidney disease (CKD). Similar approaches could be considered for clinical trials in kidney transplantation, although several factors should be taken into account. The present Consensus Report was developed from documentation produced by the European Society for Organ Transplantation (ESOT) as part of a Broad Scientific Advice request that ESOT submitted to the EMA in 2020. This paper provides a contemporary discussion of primary endpoints used in clinical trials involving CKD, including proteinuria and albuminuria, and evaluates the validity of these concepts as endpoints for clinical trials in kidney transplantation.


Subject(s)
Kidney Transplantation , Renal Insufficiency, Chronic , Albuminuria , Allografts , Disease Progression , Glomerular Filtration Rate , Humans
10.
Transpl Int ; 35: 10915, 2022.
Article in English | MEDLINE | ID: mdl-36406781

ABSTRACT

The European Society for Organ Transplantation (ESOT) has created a platform for the development of rigorous and regularly updated evidence based guidelines for clinical practice in the transplantation field. A dedicated Guideline Taskforce, including ESOT-council members, a representative from the Centre for Evidence in Transplantation, editors of the journal Transplant International has developed transparent procedures to guide the development of guidelines, recommendations, and consensus statements. During ESOT's first Consensus Conference in November 2022, leading experts will present in-depth evidence based reviews of nine themes and will propose recommendations aimed at reaching a consensus after public discussion and assessment by an independent jury. All recommendations and consensus statements produced for the nine selected topics will be published including the entire evidence-based consensus-finding process. An extensive literature review of each topic was conducted to provide final evidence and/or expert opinion.


Subject(s)
Organ Transplantation , Humans , Consensus , Societies, Medical
11.
Am J Transplant ; 21 Suppl 3: 17-59, 2021 09.
Article in English | MEDLINE | ID: mdl-34245223

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 1 , Kidney Transplantation , Pancreas Transplantation , Graft Survival , Humans , Quality of Life , Renal Dialysis
12.
Ann Vasc Surg ; 77: 349.e5-349.e18, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34437957

ABSTRACT

OBJECTIVES: Renal artery aneurysm (RAA) is a rare vascular disease. Kidney autotransplantation (KAT) is the treatment option when endovascular approach is not available. However, the evidence on KAT for RAA is mostly limited to small case series or reports. Here, we describe our 2 center experience of KAT for RAA, and provide the results of our systematic literature review to evaluate the outcomes. METHODS: A retrospective 2 center study was conducted in patients undergoing KAT for RAA between 2010 and 2018. Moreover, a systematic review was performed on medical databases to evaluate the outcomes of KAT for RAA. RESULTS: Nine patients were surgically treated at our institutions: eight with laparoscopic nephrectomy (LN), and 1 with open followed heterotopic KAT. All RAAs were ex-vivo reconstructed, and in 3 cases a vein graft was used for reconstruction. There were 2 postoperative major complications including 1 graft loss. In the systematic review, 102 studies with 355 patients were included. In 35 patients (9.9%) a minimal invasive approach was performed. The incidence of postoperative major complications and graft loss was 9.4% and 4.1%. CONCLUSIONS: Our experiences showed that laparoscopic approach for nephrectomy followed heterotopic KAT was feasible with good postoperative outcomes. KAT is an effective treatment for RAA when endovascular approach is not feasible for interpretation of the outcomes, the quality and sample size of the evidence should be taken into consideration.


Subject(s)
Aneurysm/surgery , Kidney Transplantation , Laparoscopy , Nephrectomy , Renal Artery/transplantation , Aged , Aneurysm/diagnostic imaging , Female , Graft Survival , Humans , Italy , Kidney Transplantation/adverse effects , Laparoscopy/adverse effects , Male , Middle Aged , Nephrectomy/adverse effects , Netherlands , Postoperative Complications/etiology , Renal Artery/diagnostic imaging , Retrospective Studies , Transplantation, Autologous , Treatment Outcome
13.
Eur J Appl Physiol ; 121(7): 2005-2013, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33811560

ABSTRACT

PURPOSE: Aerobic exercise capacity is reduced in patients with chronic kidney disease, partly due to alterations at the muscular and microvascular level. This study evaluated oxygen uptake (VO2) kinetics as indicator of muscular oxidative metabolism in a population of Kidney Transplant Recipients (KTRs). METHODS: Two groups of KTRs enrolled 3 (n = 21) and 12 months (n = 14) after transplantation and a control group of healthy young adults (n = 16) underwent cardiopulmonary exercise testing on cycle-ergometer. The protocol consisted in two subsequent constant, moderate-load exercise phases with a final incremental test until exhaustion. RESULTS: The time constant of VO2 kinetics was slower in KTRs at 3 and 12 months after transplantation compared to controls (50.4 ± 13.1 s and 43.8 ± 11.6 s vs 28.9 ± 8.4 s, respectively; P < 0.01). Peak VO2 was lower in KTRs evaluated 3 months after transplantation compared to patients evaluated after 1 year (21.3 ± 4.3 and 26.4 ± 8.0 mL/kg/min; P = 0.04). Blood haemoglobin (Hb) concentration was higher in KTRs evaluated at 12 months (12.8 ± 1.7 vs 14.6 ± 1.7 g/dL; P < 0.01). Among KTRs, τ showed a moderate negative correlation with Peak VO2 (ρ = - 0.52) and Oxygen uptake efficiency slope (OUES) (r = - 0.57) while no significant correlation with Hb and peak heart rate. CONCLUSIONS: KTRs show slower VO2 kinetics compared to healthy controls. Hb and peak VO2 seem to improve during the first year after transplantation. VO2 kinetics were significantly associated with indices of cardiorespiratory fitness, but less with central determinants of aerobic capacity, thus suggesting a potential usefulness of adding this index of muscular oxidative metabolism to functional evaluation in KTRs.


Subject(s)
Kidney Transplantation , Oxygen Consumption/physiology , Adult , Case-Control Studies , Exercise Test , Exercise Tolerance/physiology , Female , Humans , Male , Middle Aged
14.
Am J Transplant ; 20(11): 3140-3148, 2020 11.
Article in English | MEDLINE | ID: mdl-32649791

ABSTRACT

Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID-19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.


Subject(s)
COVID-19/epidemiology , Graft Rejection/prevention & control , Immunosuppression Therapy/methods , Kidney Transplantation/statistics & numerical data , Pandemics , SARS-CoV-2 , Transplant Recipients , Aged , Comorbidity , Europe/epidemiology , Female , Follow-Up Studies , Graft Rejection/epidemiology , Humans , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , North America/epidemiology , Retrospective Studies
15.
Transpl Int ; 33(10): 1177-1184, 2020 10.
Article in English | MEDLINE | ID: mdl-32772429

ABSTRACT

Kidney paired donation (KPD) is a valuable way to overcome immunological incompatibility in the context of living donation, and several strategies have been implemented to boost its development. In this article, we reviewed the current state of the art in this field, with a particular focus on advanced KPD strategies, including the most recent idea of initiating living donor (LD) transplantation chains with a deceased donor (DD) kidney, first applied successfully in 2018. Since then, Italy has been running a national programme in which a chain-initiating kidney is selected from a DD pool and allocated to a recipient with an incompatible LD, and the LD's kidney is transplanted into a patient on the waiting list (WL). At this stage, since the ethical and logistic issues have been managed appropriately, KPD starting with a DD has proved to be a feasible strategy. It enables transplants in recipients of incompatible pairs without the need for desensitizing and also benefits patients on the WL who are allocated chain-ending kidneys from LDs (prioritizing sensitized patients and those on the WL for longer).


Subject(s)
Kidney Transplantation , Tissue and Organ Procurement , Humans , Italy , Kidney , Living Donors
16.
Nephrol Dial Transplant ; 34(1): 157-166, 2019 01 01.
Article in English | MEDLINE | ID: mdl-30059989

ABSTRACT

Background: Malignancies represent the third leading cause of post-transplant mortality worldwide. The main challenge for transplant physicians is a timely diagnosis of this condition. The aim of the study was to identify a soluble diagnostic marker for monitoring the development of post-transplant malignancies. Methods: This is a multicentre, observational, perspective, case-control study. We enrolled 47 patients with post-transplant solid neoplasia. As a control group we employed 106 transplant recipients without a history of neoplasia and matched them with cases for the main demographic and clinical features. We investigated the transcriptomic profiles of peripheral blood mononuclear cells from kidney graft recipients with and without post-transplant malignancies enrolled in two of the participating centres, randomly selected from the whole study population. Microarray results were confirmed by quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) in the remaining patients from the same transplant centres and validated in a further independent group enrolled in two different transplant centres. Results: We identified 535 differentially expressed genes comparing patients with and without post-transplant malignancies (fold change ≥2.5; false discovery rate <5%). The cancer pathway was closely related to gene expression data, and one of the most down-regulated genes in this pathway was interleukin-27 (IL-27), a cytokine regulating anti-tumour immunity. Quantitative PCR and ELISA confirmed the microarray data. Interestingly, IL-27 plasma levels were able to discriminate patients with post-transplant neoplasia with a specificity of 80% and a sensitivity of 81%. This observation was confirmed in an independent set of patients from two different transplant centres. Conclusions: Our data suggest that IL-27 may represent a potential immunological marker for the timely identification of post-transplant neoplasia.


Subject(s)
Biomarkers/metabolism , Interleukins/metabolism , Kidney Transplantation/adverse effects , Leukocytes, Mononuclear/metabolism , Neoplasms/diagnosis , Postoperative Complications/diagnosis , Transcriptome , Age of Onset , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Neoplasms/etiology , Neoplasms/metabolism , Postoperative Complications/etiology , Postoperative Complications/metabolism , Prognosis , Transplant Recipients
17.
BMC Nephrol ; 20(1): 107, 2019 03 28.
Article in English | MEDLINE | ID: mdl-30922296

ABSTRACT

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). Person-years (PYs) were calculated from 30 days after the date of first dialysis to the date of DNM diagnosis, kidney transplant, death, last follow-up or December 31, 2013, whichever came first. The risk of DNM, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: During 10,798 PYs, 357 DNMs were diagnosed in 330 dialysis patients. A higher than expected risk of 1.3-fold was found for all DNMs combined (95% CI: 1.15-1.43). The risk was particularly high in younger dialysis patients (SIR = 1.88, 95% CI: 1.42-2.45 for age 40-59 years), and it decreased with age. Moreover, significantly increased DNM risks emerged during the first 3 years since dialysis initiation, especially within the first year (SIR = 8.52, 95% CI: 6.89-10.41). Elevated excess risks were observed for kidney (SIR = 3.18; 95% CI: 2.06-4.69), skin non-melanoma (SIR = 1.81, 95% CI: 1.46-2.22), oral cavity (SIR = 2.42, 95% CI: 1.36-4.00), and Kaposi's sarcoma (SIR = 10.29, 95% CI: 1.25-37.16). CONCLUSIONS: The elevated risk for DNM herein documented suggest the need to implement a targeted approach to cancer prevention and control in dialysis patients.


Subject(s)
Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Neoplasms/epidemiology , Population Surveillance , Renal Dialysis/adverse effects , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Italy/epidemiology , Kidney Failure, Chronic/diagnosis , Male , Middle Aged , Neoplasms/diagnosis , Population Surveillance/methods , Registries , Renal Dialysis/trends , Risk Factors
18.
Am J Transplant ; 17(12): 3159-3171, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28792681

ABSTRACT

To assess whether biopsy-guided selection of kidneys from very old brain-dead donors enables more successful transplantations, the authors of this multicenter, observational study compared graft survival between 37 recipients of 1 or 2 histologically evaluated kidneys from donors older than 80 years and 198 reference-recipients of non-histologically evaluated single grafts from donors aged 60 years and younger (transplantation period: 2006-2013 at 3 Italian centers). During a median (interquartile range) of 25 (13-42) months, 2 recipients (5.4%) and 10 reference-recipients (5.1%) required dialysis (crude and donor age- and sex-adjusted hazard ratio [95% confidence interval] 1.55 [0.34-7.12], P = .576 and 1.41 [0.10-19.54], P = .798, respectively). Shared frailty analyses confirmed similar outcomes in a 1:2 propensity score study comparing recipients with 74 reference-recipients matched by center, year, donor, and recipient sex and age. Serum creatinine was similar across groups during 84-month follow-up. Recipients had remarkably shorter waiting times than did reference-recipients and matched reference-recipients (7.5 [4.0-19.5] vs 36 [19-56] and 40 [24-56] months, respectively, P < .0001 for both comparisons). Mean (± SD) kidney donor risk index was 2.57 ± 0.32 in recipients vs 1.09 ± 0.24 and 1.14 ± 0.24 in reference-recipients and matched reference-recipients (P < .0001 for both comparisons). Adverse events were similar across groups. Biopsy-guided allocation of kidneys from octogenarian donors permits further expansion of the donor organ pool and faster access to a kidney transplant, without increasing the risk of premature graft failure.


Subject(s)
Graft Rejection/mortality , Kidney Failure, Chronic/surgery , Kidney Transplantation/mortality , Patient Selection , Postoperative Complications/mortality , Tissue Donors , Tissue and Organ Procurement/methods , Age Factors , Aged , Case-Control Studies , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/etiology , Graft Survival , Humans , Kidney Function Tests , Kidney Transplantation/adverse effects , Male , Middle Aged , Prognosis , Risk Factors , Survival Rate
19.
Nephrol Dial Transplant ; 32(12): 2126-2131, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29077866

ABSTRACT

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.


Subject(s)
Donor Selection , Hospitals, High-Volume/statistics & numerical data , Hospitals, Low-Volume/statistics & numerical data , Kidney Transplantation/methods , Kidney/anatomy & histology , Living Donors , Nephrectomy/methods , Tissue and Organ Harvesting/methods , Female , Graft Survival , Humans , Kidney/blood supply , Kidney/surgery , Male , Middle Aged , Time Factors
20.
Clin Transplant ; 31(10)2017 Oct.
Article in English | MEDLINE | ID: mdl-28640530

ABSTRACT

The aging of the on-dialysis population raises the issue of whether to propose elderly patients for kidney transplantation and how to manage their immunosuppression. This study aimed to analyze the outcome of kidney transplantation on an Italian series of elderly recipients. We included in this retrospective study all patients over 60 years, receiving a deceased-donor kidney transplantation from January 2004 to December 2014 in two north Italian Centers. We analyzed the correlation of recipient age with graft's and patient's survival, delayed graft function, acute cellular rejection (ACR), surgical complications, infections, and glomerular filtration rate. Four hundred and fifty-two patients with a median age of 65 years were included in the study. One-, 3-, and 5-year patient's and graft's survival were, respectively, of 98.7%, 93%, 89% and 94.4%, 87.9%, 81.4%. The increasing recipient age was an independent risk factor only for the patient's (P=.008) and graft's survival (P=.002). ACR and neoplasia were also associated to a worse graft survival. The reduced graft survival in elderly kidney recipients seems to be related more to the increasing recipient's age than to the donor's features. In this population, the optimization of organ allocation and immunosuppression may be the key factors to endorse improvements.


Subject(s)
Graft Rejection/mortality , Kidney Failure, Chronic/mortality , Kidney Transplantation/mortality , Postoperative Complications/mortality , Transplant Recipients/statistics & numerical data , Age Factors , Aged , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/epidemiology , Graft Survival , Humans , Kidney Failure, Chronic/surgery , Kidney Function Tests , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
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