Physiopathological role of extracellular vesicles in alloimmunity and kidney transplantation and their use as biomarkers

Antibody-mediated rejection is the leading cause of kidney graft dysfunction. The process of diagnosing it requires the performance of an invasive biopsy and subsequent histological examination. Early and sensitive biomarkers of graft damage and alloimmunity are needed to identify graft injury and eventually limit the need for a kidney biopsy. Moreover, other scenarios such as delayed graft function or interstitial fibrosis and tubular atrophy face the same problem. In recent years, interest has grown around extracellular vesicles, specifically exosomes actively secreted by immune cells, which are intercellular communicators and have shown biological significance. This review presents their potential as biomarkers in kidney transplantation and alloimmunity

Use of Anti-Cytokine Therapy in Kidney Transplant Recipients with COVID-19

In the context of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to evaluate the impact of anti-cytokine therapies (AT) in kidney transplant recipients requiring hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is an observational retrospective study, which included patients from March to May 2020. An inverse probability of treatment weighting from a propensity score to receive AT was used in all statistical analyses, and we applied a bootstrap procedure in order to calculate an estimation of the 2.5th and 97.5th percentiles of odds ratio (OR). outcomes were measured using an ordinal scale determination (OSD). A total of 33 kidney recipients required hospitalization and 54% of them received at least one AT, mainly tocilizumab (42%), followed by anakinra (12%). There was no statistical effect in terms of intensive care unit (ICU) admission, respiratory secondary infections (35% vs. 7%) or mortality (16% vs. 13%) comparing patients that received AT with those who did not. Nevertheless, patients who received AT presented better outcomes during hospitalization in terms of OSD ≥5 ((OR 0.31; 2.5th, 97.5th percentiles (0.10; 0.72)). These analyses indicate, as a plausible hypothesis, that the use of AT in kidney transplant recipients presenting with COVID-19 could be beneficial, even though multicenter randomized control trials using these therapies in transplanted patients are needed

Uso terapéutico de las vesículas extracelulares en insuficiencia renal aguda y crónica

En la década de los 90 se descubrió un nuevo sistema de comunicación célula-célula, que consiste en la liberación de vesículas cargadas con partículas bioactivas (proteínas, mRNA, miRNA, metabolitos, etc.) en el espacio extracelular. Este tipo de comunicación se ha conservado durante la evolución, hecho que justificaría que la mayoría de los tipos celulares puedan generarlas. Estas vesículas extracelulares (VE) pueden regular diversos procesos fisiológicos, así como el desarrollo y progresión de enfermedades. En los últimos anos se ha extendido el estudio de las VE generadas principalmente por células madre adultas o embrionarias, células sanguíneas, células del sistema inmune y nervioso, así como células tumorales. El análisis de VE en fluidos corporales ha sido utilizado como herramienta de diagnóstico en cáncer y recientemente para distintas enfermedades renales. Sin embargo, en esta revisión pretendemos analizar la importancia, función y posible aplicación clínica de las VE generadas por células madre en enfermedades renales y en trasplantes

Advantages of plasmatic CXCL-10 as a prognostic and diagnostic biomarker for the risk of rejection and subclinical rejection in kidney transplantation

This study evaluate the potential of plasmatic CXCL-10 (pCXCL-10) as a pre&post transplantation prognostic and diagnostic biomarker of T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR) and subclinical rejection (SCR) risk in adult kidney recipients considering BKV and CMV infections as possible clinical confounder factors. Twenty-eight of 100 patients included experienced rejection (TCMR:14; ABMR:14); 8 SCR; 13 and 16 were diagnosed with BKV and CMV infection, respectively. Pre-transplantation pCXCL-10 was significantly increased in TCMR and ABMR and post-transplantation in TCMR, ABMR and SCR compared with nonrejectors. All CMV+ patients showed pCXCL-10 levels above the cutoff values established for rejection whereas the 80% of BKV+ patients showed pCXCL-10 concentration < 100 pg/mL. pCXCL-10 could improve pre-transplantation patient stratification and immunosuppressive treatment selection according to rejection risk; and after kidney transplantation could be a potential early prognostic biomarker for rejection. Clinical confounding factor in BKV+ and particularly in CMV+ patients must be discarded

Kidney Transplantation Group of the Spanish Society of Nephrology

Document publicat també en castellàThe Board of Directors of the Spanish Society of Nephrology (S.E.N.) approved at its ordinary meeting of 18 December 2012 the creation of a Transplantation Working Group (SENTRA). In accordance with the Regulations of the S.E.N. Working Groups, in promoting the establishment of a working group, four priority aspects must be addressed..

Results and Lessons Learned on Robotic Assisted Kidney Transplantation

Introduction. Nowadays, minimally invasive surgery in kidney transplantation is a reality thanks to robotic assistance. In this paper, we describe our experience, how we developed the robotic assisted Kidney transplantation (RAKT) technique, and analyze our results. Material and Methods. This is a retrospective study of all RAKTs performed at our center between July 2015 and March 2020. We describe the donor selection, surgical technique, and analyze the surgical results and complications. A comparison between the first 20 cases and the following ones is performed. Results. During the aforementioned period, 82 living donor RAKTs were performed. The mean age was and 50 (61%) were male. Mean body mass index was and preemptive in 63.7% of cases. Right kidneys and multiple arteries were seen in 14.6% and 12.2%, respectively. Mean operative and rewarming time was and minutes, respectively. Five cases required conversion to open surgery because of abnormal kidney vascularization. Two patients required embolization for subcapsular and hypogastric artery bleeding without repercussion. Three kidneys were lost, two of them due to acute rejection and one because venous thrombosis. Late complications requiring surgery included one kidney artery stenosis, one ureteral stenosis, two lymphoceles, and three hernia repairs. We noticed a significant reduction in time between the first 20 cases and the following ones from to (). With a mean follow-up time of 1.8 years (SD 1.3), the mean creatinine was 1.52 (SD 0.7) and RAKT graft survival was 98%. Conclusions. The robotic approach is an attractive, minimally invasive method for kidney transplantation, yielding good results. Further studies are needed to consider it a standard approach

Rituximab, plasma exchange and immunoglobulins: an ineffective treatment for chronic active antibody-mediated rejection

BACKGROUND: Chronic active antibody-mediated rejection (c-aABMR) is an important cause of allograft failure and graft loss in long-term kidney transplants. METHODS: To determine the efficacy and safety of combined therapy with rituximab, plasma exchange (PE) and intravenous immunoglobulins (IVIG), a cohort of patients with transplant glomerulopathy (TG) that met criteria of active cABMR, according to BANFF'17 classification, was identified. RESULTS: We identified 62 patients with active c-aABMR and TG (cg ≥ 1). Twenty-three patients were treated with the combination therapy and, 39 patients did not receive treatment and were considered the control group. There were no significant differences in the graft survival between the two groups. The number of graft losses at 12 and 24 months and the decline of eGFR were not different and independent of the treatment. A decrease of eGFR≥13 ml/min between 6 months before and c-aABMR diagnosis, was an independent risk factor for graft loss at 24 months (OR = 5; P = 0.01). Infections that required hospitalization during the first year after c-aABMR diagnosis were significantly more frequent in treated patients (OR = 4.22; P = 0.013), with a ratio infection/patient-year of 0.65 and 0.20 respectively. CONCLUSIONS: Treatment with rituximab, PE, and IVIG in kidney transplants with c-aABMR did not improve graft survival and was associated with a significant increase in severe infectious complications

Validation of Backtable Graft Arterial Anastomosis Between Splenic Artery and Superior Mesenteric Artery: A 21-year Single-center Experience of Pancreas Transplantation

Resumen del trabajo presentado en el IPITA 2021 VIRTUAL CONGRESS, celebrado de forma virtual del 20 al 23 de octubre de 2021Aim: To determine the role of the arterial spleno-mesenteric anastomosis reconstruction technique compared to other types of backtable arterial anastomosis, in terms of vascular complications and long-term patient and graft survival in a single institution. Methods: Retrospective analysis including all pancreas transplants performed over 21 years (1999–2019). For the bench reconstruction: (1) the distal superior mesenteric artery (SMA) was distally dissected and sewn to the splenic artery (SA), or (2) the arteries were reconstructed with an iliac arterial “Y” graft. Results: A total of 412 pancreas transplantations were done. At the bench procedure SMA/SA anastomosis was performed in 376 of patients, arterial iliac “Y” graft in 32 of patients, and no arterial reconstruction was required in 4 of patients. A total of 90 patients presented vascular complications within the 30 days following transplant: (venous (n=64), arterial (n=11), both (n=15), without statistically significant differences between the SMA/SA anastomosis group and others. Regarding acute arterial events:(1) for the SMA/SA anastomosis group, a total of 24 patients presented with thrombosis (n=16), stenosis (n=5), pseudoaneurysm (n=2); (2) for the iliac “Y” graft group, there were 3 patients with thrombosis. Focusing on chronic arterial events:(1)for the SMA/SA anastomosis group, a total of 2 patients presented with chronic thrombosis, 2 with pseudoaneurysm, 2 with arterioenteral fistula and one with arteriovenous fistula;(2)for the iliac “Y” graft group, and one patient with arterioenteral fistula. After a median follow-up of 129.2 [77.2–182] months, no statically differences were found between SMA/SA anastomosis and iliac “Y” graft arterial reconstruction groups at 1, 3, 5 and 10 years in terms of patient and graft survival. Conclusions: The back table procedure used in our institution (SMA/SA) is an easy, effective and safe surgical technique that can be used as the first option for arterial reconstruction or as a good alternative for surgeons to the widely used arterial “Y” graft.Peer reviewe

Patient Experience in Pancreas-Kidney Transplantation-A Methodological Approach Towards Innovation in an Established Program

Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components

Psychosocial risk factors for impaired health‑related quality of life in living kidney donors: results from the ELIPSY prospective study

Living kidney donors' follow-up is usually focused on the assessment of the surgical and medical outcomes. Whilst the psychosocial follow-up is advocated in literature. It is still not entirely clear which exact psychosocial factors are related to a poor psychosocial outcome of donors. The aim of our study is to prospectively assess the donors' psychosocial risks factors to impaired health-related quality of life at 1-year post-donation and link their psychosocial profile before donation with their respective outcomes. The influence of the recipient's medical outcomes on their donor's psychosocial outcome was also examined. Sixty donors completed a battery of standardized psychometric instruments (quality of life, mental health, coping strategies, personality, socio-economic status), and ad hoc items regarding the donation process (e.g., motivations for donation, decision-making, risk assessment, and donor-recipient relationship). Donors' 1-year psychosocial follow-up was favorable and comparable with the general population. So far, cluster-analysis identified a subgroup of donors (28%) with a post-donation reduction of their health-related quality of life. This subgroup expressed comparatively to the rest, the need for more pre-donation information regarding surgery risks, and elevated fear of losing the recipient and commitment to stop their suffering