Kinetic of the CMV-specific T-cell immune response and CMV infection in CMV-seropositive kidney transplant recipients receiving rabbit anti-thymocyte globulin induction therapy: A pilot study.

BACKGROUND: Some studies have suggested that rATG treatment may be associated with an increased incidence of CMV infection and delayed CMV immune response. However, the evidences supporting this matter are scarce. This study aims to characterize the kinetic of the CMV-specific T-cell immune response before and after rATG induction therapy and the relationship with the development of CMV infection in CMV-seropositive kidney transplant recipients. METHODS: An observational prospective study of CMV-seropositive kidney transplant patients that received rATG induction therapy was performed. A pretransplant sample was obtained before the surgery to determine the CMV-specific immunity. CMV viral load (by PCR) and CMV-specific T-cell immune response (by flow cytometry) were determined during the follow-up at 0.5, 1, 2, 3, 6, and 12 months post transplantation. RESULTS: A total of 23 patients were included in the study. CMV prophylaxis was administrated for a media of 90 days after transplantation. At the end of follow-up, 18 (78.3%) patients had CMV-specific immunity with a median value of 0.31% CD8+ CD69+ INF-γ+ T cells at a median of 16 weeks post transplantation. Five patients never acquired CMV-specific immunity. No statistically significant association between CMV infection and CMV-specific T-cell immune response (P = .086) was observed. However, patients with positive pretransplant CMV-specific immunity developed earlier immunity and achieved higher levels of CD8+ CD69+ INF-γ+ T-cell post-transplantation than patients with negative pretransplant immunity. CONCLUSIONS: CMV-specific immune monitoring in addition to CMV-serology may be useful to stratify patient's risk of CMV infection before transplantation.

Acidic Urine pH and Clinical Outcome of Lower Urinary Tract Infection in Kidney Transplant Recipients Treated with Ciprofloxacin and Fosfomycin.

Different factors, including antimicrobial resistance, may diminish the effectiveness of antibiotic therapy, challenging the management of post-transplant urinary tract infection (UTI). The association of acidic urine pH with microbiological and clinical outcomes was evaluated after fosfomycin or ciprofloxacin therapy in 184 kidney transplant recipients (KTRs) with UTI episodes by Escherichia coli (N = 115) and Klebsiella pneumoniae (N = 69). Initial urine pH, antimicrobial therapy, and clinical and microbiological outcomes, and one- and six-month follow-up were assessed. Fosfomycin was prescribed in 88 (76.5%) E. coli and 46 (66.7%) K. pneumoniae UTI episodes in the total cohort. When the urine pH ≤ 6, fosfomycin was prescribed in 60 (52.2%) E. coli and 29 (42.0%) K. pneumoniae. Initial urine pH ≤ 6 in E. coli UTI was associated with symptomatic episodes (8/60 vs. 0/55, p = 0.04) at one-month follow-up, with a similar trend in those patients receiving fosfomycin (7/47 vs. 0/41, p = 0.09). Acidic urine pH was not associated with microbiological or clinical cure in K. pneumoniae UTI. At pH 5, the ciprofloxacin MIC90 increased from 8 to >8 mg/L in E. coli and from 4 to >8 mg/L in K. pneumoniae. At pH 5, the fosfomycin MIC90 decreased from 8 to 4 mg/L in E. coli and from 512 to 128 mg/L in K. pneumoniae. Acidic urine is not associated with the microbiological efficacy of fosfomycin and ciprofloxacin in KTRs with UTI, but it is associated with symptomatic UTI episodes at one-month follow-up in E. coli episodes.

Changes over time in the causes of death with a functioning graft in kidney transplantation recipients.

INTRODUCTION: Death with a functioning graft (DWFG) is the most frequent cause of loss of kidney transplantation (KT). OBJECTIVE: To analyze the evolution of the causes of DWFG and the frequency of the types of cancer causing DWFG. METHODS: Retrospective study of KT in Andalusia from 1984 to 2018. We analyzed the evolution according to eras (1984-1995; 1996-2007; 2008-2018) and according to post-transplant period (early death: first year post-KT; late death: after first year post-KT). RESULTS: A total of 9905 KT were performed, registering 1861 DWFG. The most frequent causes were cardiovascular disease (25.1%), infections (21.5%) and cancer (19.9%). In early death we did not observe changes, and infections were always the main cause. In late death, cardiovascular death decreased (1984-1995: 35.2%, 1996-2007: 22.6%, 2008-2018: 23.9%), but infections (1984-1995: 12.5%, 1996-2007: 18.3%, 2008-2018: 19.9%) and, above all, cancer-related deaths increased (1984-1995: 21.8%, 1996-2007: 29%, 2008-2018: 26.8%) (P < .001). In the multivariable analysis for late death due to cardiovascular disease, recipient age, retransplantation, diabetes, and the first period were risk factors, while the risk of late death due to cancer and infections was associated with recent eras. In the first year after transplantation, the most frequent neoplasia causing DWFG was post-transplant lymphoproliferative disease, and after the first year, it was lung cancer, without differences when it was analyzed by eras. CONCLUSIONS: Despite the greater comorbidity of the recipients, cardiovascular deaths have decreased. Cancer has been the main cause of late death in recent years. Lung cancer is the most frequent malignancy that causes DWFG in our transplant patients.

Live donor kidney transplantation. Situation analysis and roadmap.

Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spainhave adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.

Recommendations for living donor kidney transplantation.

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.

Impact of Treating Asymptomatic Bacteriuria in Kidney Transplant Recipients: A Prospective Cohort Study.

This study aims to define the epidemiologic, clinical, and microbiological features of asymptomatic bacteriuria (AB) and cystitis in kidney transplantation recipients (KTRs), and to determine the impact of antimicrobial therapy of AB and the risk factors of cystitis. We conducted a prospective observational study of AB and cystitis in KTRs from January to June 2017. One-hundred ninety seven KTRs were included: 175 (88.8%) with AB and 22 (11.2%) with cystitis. The most frequent etiologies were Escherichia coli, Klebsiellapneumoniae, Enterococcusfaecalis, and Pseudomonas aeruginosa. No differences were observed regarding the etiologies, antimicrobial susceptibility patterns, and microbiologic outcomes in AB vs. cystitis. The treatment of AB diminished the microbiological cure and increased the rates of microbiologic relapses and reinfections; in addition, treated AB patients showed a trend of developing symptomatic urinary tract infection in the following six months. The analysis of the data identified the following independent risk factors for cystitis during the six months of follow-up: AB treatment, thymoglobulin induction, previous acute pyelonephritis, and time since transplantation < 1 year. In summary, considering the lack of clinical benefits of treating AB and its impact on cystitis development in the follow-up, we support the recommendation of not screening for or treating AB.

COVID-19 in Solid Organ Transplant Recipients in Spain Throughout 2020: Catching the Wave?

BACKGROUND: Few studies have analyzed differences in clinical presentation and outcomes in solid organ transplant (SOT) recipients with coronavirus disease 2019 (COVID-19) across different pandemic waves. METHODS: In this multicenter, nationwide, prospective study, we compared demographics and clinical features, therapeutic management, and outcomes in SOT recipients diagnosed with COVID-19 in Spain before (first wave) or after (second wave) 13 July 2020. RESULTS: Of 1634 SOT recipients, 690 (42.2%) and 944 (57.8%) were diagnosed during the first and second periods, respectively. Compared with the first wave, recipients in the second were younger (median: 63 y [interquartile range, IQR: 53-71] versus 59 y [IQR: 49-68]; P < 0.001) and less likely to receive anti-severe acute respiratory syndrome coronavirus 2 drugs (81.8% versus 8.1%; P < 0.001), with no differences in immunomodulatory therapies (46.8% versus 47.0%; P = 0.931). Adjustment of immunosuppression was less common during the second period (76.4% versus 53.6%; P < 0.001). Hospital admission (86.7% versus 58.1%; P < 0.001), occurrence of acute respiratory distress syndrome (34.1% versus 21.0%; P < 0.001), and case-fatality rate (25.8% versus 16.7%; P < 0.001) were lower in the second period. In multivariate analysis, acquiring COVID-19 during the first wave was associated with an increased risk of death (OR: 1.47; 95% confidence interval [CI], 1.12-1.93; P = 0.005), although this impact was lost in the subgroup of patients requiring hospital (OR: 0.97; 95% CI, 0.73-1.29; P = 0.873) or intensive care unit admission (OR: 0.65; 95% CI, 0.35-1.18; P = 0.157). CONCLUSIONS: We observed meaningful changes in demographics, therapeutic approaches, level of care, and outcomes between the first and second pandemic waves. However, outcomes have not improved in the more severe cases of posttransplant COVID-19.

Live donor kidney transplantation. Situation analysis and roadmap. / Trasplante renal de donante vivo. Análisis de situación y hoja de ruta.

Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spain have adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.

Donor-specific antibodies against HLA, MICA, and GSTT1 in patients with allograft rejection and C4d deposition in renal biopsies.

BACKGROUND: Production of antibodies against donor-specific antigens is one of the central mechanisms of allograft rejection. This antibody-mediated rejection (AMR) is evidenced by the presence of circulating donor-specific antibodies and deposition of complement component C4d on renal endothelium. Although anti-human leukocyte antigen (HLA) antibodies account for a high proportion of AMR, in many cases anti-HLA antibodies cannot be demonstrated. In liver transplant, antibodies against glutathione-S-transferase T1 (GSTT1) expressed on the graft may induce an antibody response leading to a severe graft dysfunction. In addition, presence of antibodies against major-histocompatibility-complex class I chain-related gene A (MICA) has been associated with a poor graft survival in kidney transplantation. METHODS: Pre- and posttransplantation sera from 19 patients fulfilling the criteria for AMR including C4d deposition in renal biopsies were included. Donor-specific antibodies against HLA-I and -II and MICA were studied using Luminex. Anti-GSTT1 antibodies were analyzed by indirect immunofluorescence and by an ELISA method. A control group of 39 patients with graft dysfunction negative for C4d was also included. RESULTS: At the time of the biopsy, 4 (21%) patients had only anti-HLA class I antibodies; 3 (15.8%) had anti-GSTT1, 2 (10.5%) had anti-HLA-class II, and 2 (10.5%) had anti-MICA; four patients had combination of antibodies: HLA-I + MICA (n=1), HLA-I + GSTT1 (n=2), and GSTT1+MICA (n=1). No antibodies were found in 4 (21%) patients. In total, 6 (31.6%) C4d+ patients had anti-GSTT1 antibodies, whereas, among the 39 C4d-negative patients, only 3 (7.7%) had anti-GSTT1 antibodies (P=0.027). CONCLUSION: Besides anti-HLA antibodies, donor-specific antibodies against MICA and GSTT1 antigens could be responsible for the occurrence of antibody-mediated kidney graft rejection.

Características del sometimiento presente en secuestros extorsivos desde la percepción de los / Characteristics of the present submission in extorsivos kidnappings from the perception of professionals who toil in the Group of Action Unified by the Personal Freedom, GAULA, Cundinamarca

El presente estudio tiene por objetivo conocer las característicasdel sometimiento en el secuestro extorsivocometido por grupos al margen de la ley, a partir deencuestas aplicadas a los profesionales que laboran enlos grupos de acción unificada por la libertad personal,GAULA, militar y de la Policía Nacional. Se utilizó undiseño descriptivo de tipo no experimental,transaccional. La hipótesis del estudio busca comprobarla existencia de diferencias en las estrategias empleadaspor los diferentes grupos ilegales para sometera sus víctimas. Los resultados permitieron establecerque la existencia de diferencias en las característicasdel sometimiento presentes en secuestros extorsivos nodepende de la organización a la que pertenece el grupocaptor, sino del lugar de operaciones de éste, independientementede su pertenencia a una organización parael caso de la subversión y las autodefensas...

Lesiones impalpables del seno: localización mamográfica y biopsia: análisis de 164 anormalidades / Impalpable lesions of the breast: Mammographic localization and biopsy: analysis of 164 abnormalities

La biopsia guiada mediante mamografía en lesiones ocultas del seno es una herramienta útil para el diagnóstico temprano del cáncer y las lesiones premalignas. En esta revisión de 164 pacientes con lesiones no palpables detectadas mediante este procedimiento durante un período de dos años, a quienes se realizó marcación con arpón y resección quirúrgica, se diagnosticó malignidad en 42 pacientes (25,6%), trece de ellas con carcinoma in situ (7,9%) y 29 infiltrante (17,6%). El diagnóstico benigno más frecuente en esta serie fue fibroadenoma, seguido por otras patologías benignas comunes. La categorización mamográfica según el sistema de BI-RADS muestra muy buena correlación con el diagnóstico histopatológico definitivo, evidenciando resultados homologables a otros estudios similares. Por tales hallazgos, nos permitimos recomendar esta técnica de diagnóstico temprano en nuestro medio para lesiones no palpables del seno detectadas con mamografía.