The role of advanced practice nurses in creating the kidney transplant candidate care map (APN‑preKT): a convergent‑parallel mixed methods research protocol

Background: Waiting time for kidney transplants (KT) is an important health determinant for patients with chronic kidney disease (CKD). During this time, ongoing evaluation and participation is necessary in order to guarantee the quality and suitability of the proposed treatment. There is no existing literature on the potential impact of inclusion of an Advanced Practice Nurse (APN) role in the hospital setting on care for CKD patients who are candidates for KT. The main objectives of this protocol are: to analyse outpatient nursing activity in the care of individuals with KT in Spain; to identify the needs of individuals who are KT candidates; and to measure the impact of the APN role through patient outcomes and experiences. These objectives are fulfilled through 5 specific related substudies. Methods A convergent parallel mixed methods approach will be conducted between July 2021 and April 2024. Quantitative and qualitative data will be collected and analysed separately to ascertain whether the findings confirm or contradict one another. Each of the 5 substudies of the project require a specific design, sampling method, and data collection procedure in order to meet the overall objectives for the project. Discussion: The results of the project are expected to inform the design of future nursing roles and contribute to future improvements in the quality of care provided. The data that may be obtained from this protocol are limited to the specific context of the study facility and may be extrapolated but not compared to other settings due to the variability of care pathways for KT candidates internationally

Outcomes of Frail Patients While Waiting for Kidney Transplantation : Differences between Physical Frailty Phenotype and FRAIL Scale

Frailty is associated with poorer outcomes among patients waiting for kidney transplantation (KT). Several different tools to measure frailty have been used; however, their predictive value is unknown. This is a prospective longitudinal study of 449 KT candidates evaluated for frailty by the Physical Frailty Phenotype (PFP) and the FRAIL scale. During the study period, 296 patients received a KT, while 153 remained listed. Patients who did not get receive a transplant were more frequently frail according to PFP (16.3 vs. 7.4%, p = 0.013). Robust patients had fewer hospital admissions during the 1st year after listing (20.8% if PFP = 0 vs. 43.4% if ≥1, and 27.1% if FRAIL = 0 vs. 48.9% if ≥1) and fewer cardiovascular events (than FRAIL ≥ 1) or major infectious events (than PFP ≥ 1). According to PFP, scoring 1 point had an impact on patient survival and chance of transplantation in the univariate analysis. The multivariable analysis corroborated the result, as candidates with PFP ≥ 3 had less likelihood of transplantation (HR 0.45 [0.26-0.77]). The FRAIL scale did not associate with any of these outcomes. In KT candidates, pre-frailty and frailty according to both the PFP and the FRAIL scale were associated with poorer results while listed. The PFP detected that frail patients were less likely to receive a KT, while the FRAIL scale did not

Increased mortality after kidney transplantation in mildly frail recipients

Physical Frailty Phenotype (PFP) is the most used frailty instrument among kidney transplant recipients, classifying patients as pre-frail if they have 1-2 criteria and as frail if they have ≥3. However, different definitions of robustness have been used among renal patients, including only those who have 0 criteria, or those with 0-1 criteria. Our aim was to determine the impact of one PFP criterion on transplant outcomes. We undertook a retrospective study of 296 kidney transplant recipients who had been evaluated for frailty by PFP at the time of evaluating for transplantation. Only 30.4% of patients had 0 criteria, and an additional 42.9% showed one PFP criterion. As PFP score increased, a higher percentage of women and cerebrovascular disease were found. Recipients with 0-1 criteria had lower 1-year mortality after transplant than those with ≥2 (1.8% vs 10.1%), but this difference was already present when we only considered those who scored 0 (mortality 1.1%) and 1 (mortality 2.4%) separately. The multivariable analysis confirmed that one PFP criterion was associated to a higher risk of patient death after kidney transplantation [hazard ratio 3.52 (95% confidence interval 1.03-15.9)]. Listed kidney transplant candidates frequently show only one PFP frailty criterion. This has an independent impact on patient survival after transplantation

Validation of a survival benefit estimator tool in a cohort of European kidney transplant recipients

Producción CientíficaPre-transplant prognostic scores help to optimize donor/recipient allocation and to minimize organ discard rates. Since most of these scores come from the US, direct application in non-US populations is not advisable. The Survival Benefit Estimator (SBE), built upon the Estimated Post-Transplant Survival (EPTS) and the Kidney Donor Profile Index (KDPI), has not been externally validated. We aimed to examine SBE in a cohort of Spanish kidney transplant recipients. We designed a retrospective cohortbased study of deceased-donor kidney transplants carried out in two different Spanish hospitals. Unadjusted and adjusted Cox models were applied for patient survival. Predictive models were compared using Harrell’s C statistics. SBE, EPTS and KDPI were independently associated with patient survival (p ≤ 0.01 in all models). Model discrimination measured with Harrell’s C statistics ranged from 0.57 (KDPI) to 0.69 (SBE) and 0.71 (EPTS). After adjustment, SBE presented similar calibration and discrimination power to that of EPTS. SBE tended to underestimate actual survival, mainly among high EPTS recipients/high KDPI donors. SBE performed acceptably well at discriminating posttransplant survival in a cohort of Spanish deceased-donor kidney transplant recipients, although its use as the main allocation guide, especially for high KDPI donors or high EPTS recipients requires further testing.Rio Hortega contract (ISCIII-11453)Fondo de Investigaciones Sanitarias - Fondo Europeo de Desarrollo Regional (project PI16/0617)Redinren (project RD16/0009/001

Pretransplant CMV-Specific T-Cell Immunity But Not Dose of Antithymocyte Globulin Is Associated With Recovery of Specific Immunity After Kidney Transplantation

Background: This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG. Methods: CMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-? [IFN-?] ? 0.2 IU/mL) indicated a positive CMV-CMI. Results: A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-? level (>12 IU/mL vs ?12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1-53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-? level ?12 IU/mL. Conclusions: More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-? level, but not the ATG dose, shows a strong association with the kinetics of this recovery.This work was supported by the Fundación Progreso y Salud, Consejería de Salud y Familias, Junta de Andalucía (grant number PI-0294-2014); Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (grant number CP 18/00073 to M. F. R.); Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia e Innovación, Spanish Network for Research in Infectious Diseases (grant numbers REIPI RD16/0016/0002, RD16/0016/0003, RD16/0016/0007, RD16/0016/0008, RD16/0016/0009 and RD16/0016/0012); cofinanced by European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligent Growth 2014- 2020; Spanish Network for Research in Renal Diseases (grant numbers RD16/0009/0006, RD16/0009/0008, RD16/0009/0013, RD16/0009/0014, RD16/0009/0019, RD16/0009/0034); Centro de Investigación Biomédica en Red Enfermedades Respiratorias (grant number CB06/06/0058); and Spanish Group for the Study of Infection in Transplantation and the Immunocompromised Host of the Spanish Society of Infectious Diseases and Clinical Microbiolog

Manejo de la inmunosupresión en pacientes trasplantados de riñón con COVID19. Estudio multicéntrico nacional derivado del registro COVID de la Sociedad Española de Nefrología

Introduction: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated.Objectives: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis.Material and methods: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis.Results: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 +/- 0.8, 2.1 +/- 1.2 and 1.8 +/- 1 mg/dl respectively (p < 0.001). 56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant.Conclusions: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis

Use of tocilizumab in kidney transplant recipients with COVID-1

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Monitorización sérica e histológica del rechazo mediado por anticuerpos en trasplante renal

El trasplante renal es el tratamiento de elección en los pacientes con enfermedad renal crónica avanzada porque mejora la supervivencia del paciente, su calidad de vida e implica menores costes si lo comparamos con el tratamiento sustitutivo mediante diálisis. En los últimos años, los avances en la inmunosupresión, la mejora en las técnicas quirúrgicas y el mejor conocimiento de la inmunología del trasplante han permitido incrementar la supervivencia del paciente y del injerto a corto plazo, con menor impacto en las tasas de pérdida a medio y largo plazo. Se han producido dos importantes avances en la última década: el desarrollo de nuevas técnicas de detección de anticuerpos frente a antígenos HLA y la caracterización histológica del rechazo mediado por anticuerpos. El objetivo de la presente tesis ha sido profundizar en el conocimiento del rechazo mediado por anticuerpos abordando nuevos aspectos desde estos dos puntos de vista: estudio serológico de los anticuerpos HLA y caracterización histológica del rechazo humoral. Para ello, hemos analizado una amplia cohorte de pacientes trasplantados con estudio de anticuerpos antiHLA pre y postrasplante determinados mediante tecnología Luminex. Los pacientes con anticuerpos dirigidos frente al donante detectados pretrasplante presentan una peor supervivencia del injerto y mayor riesgo de rechazo mediado por anticuerpos; y este riesgo sigue incrementado tanto si persiste como si no persiste el anticuerpo después del trasplante o aparece de novo. Por otro lado, hemos realizado el estudio de otros anticuerpos considerados clásicamente menos inmunogénicos y con poca relevancia en el campo del trasplante hasta la fecha, pero que las nuevas técnicas en fase sólida permiten identificar, como son los anticuerpos frente a los antígenos HLA DP. En nuestra experiencia, el 10% de los pacientes trasplantados presentan anticuerpos antiHLA-DP detectados por Luminex, tanto pre como postrasplante. La presencia de estos anticuerpos no parece modificar el impacto en la supervivencia del injerto. Desde el punto de vista histológico, hemos demostrado que el rechazo mediado por anticuerpos es un diagnóstico frecuente en las biopsias tardías de injerto renal realizadas por indicación según los criterios de la clasificación de Banff 2013, y confiere un peor pronóstico que otras categorías histológicas. Finalmente, hemos profundizado en el análisis de la categoría histológica de rechazo mediado por anticuerpos comparando la clasificación de Banff 2009 con la nueva definición de cambios mediados por anticuerpos de la clasificación de Banff 2013. Según nuestros resultados, la clasificación de Banff 2013 proporciona un diagnóstico más preciso del rechazo mediado por anticuerpos.Kidney transplantation is considered the treatment of choice for patients with end-stage renal disease. It is associated with improved survival, better quality of life and reduced costs when compared with dialysis. Throughout the years, the progress in immunosuppression, the improvement in surgical techniques and a better understanding of transplant immunology have produced an increase in both patient and graft survival short-term, notwithstanding in medium and long-term outcomes. Two major developments have taken place over the last decade: the development of new techniques to detect HLA antibodies, and the histological characterization of antibody-mediated rejection. The aim of this thesis has been to expand the knowledge of antibody-mediated rejection by addressing the issue from these two points of view: HLA antibody serological testing with new techniques and histological characterization of humoral rejection. To that end, we have analyzed a large cohort of transplant patients with pre and post-transplant anti-HLA antibodies determined by Luminex technologies. Patients with preformed donor specific antibodies show worse graft survival and greater risk of antibody-mediated rejection, regardless potential DSA clearing after transplantation. Furthermore, we evaluated the impact of typically less immunogenic antibodies believed to be less relevant in the transplant field thus far, such as HLA DP antibodies, albeit detectable by newer solid phase techniques. In our experience, 10% of transplant patients show HLA DP antibodies as detected by Luminex assay both pre and post-transplant. The presence of these antibodies does not seem to modify graft survival Histologically, we have shown that antibody-mediated rejection is a common diagnosis most often seen in late kidney graft biopsies according to the Banff 2013 classification criteria; antibody-mediated rejection also shows worse prognosis compared to other histological categories. Eventually, we have delved into the analysis of the antibody-mediated rejection category by comparing the Banff 2009 classification to the new antibody-mediated changes from Banff 2013. According to our results, Banff 2013 classification provides a more accurate diagnosis of antibody-mediated rejection

Monitorización sérica e histológica del rechazo mediado por anticuerpos en trasplante renal

El trasplante renal es el tratamiento de elección en los pacientes con enfermedad renal crónica avanzada porque mejora la supervivencia del paciente, su calidad de vida e implica menores costes si lo comparamos con el tratamiento sustitutivo mediante diálisis. En los últimos años, los avances en la inmunosupresión, la mejora en las técnicas quirúrgicas y el mejor conocimiento de la inmunología del trasplante han permitido incrementar la supervivencia del paciente y del injerto a corto plazo, con menor impacto en las tasas de pérdida a medio y largo plazo. Se han producido dos importantes avances en la última década: el desarrollo de nuevas técnicas de detección de anticuerpos frente a antígenos HLA y la caracterización histológica del rechazo mediado por anticuerpos. El objetivo de la presente tesis ha sido profundizar en el conocimiento del rechazo mediado por anticuerpos abordando nuevos aspectos desde estos dos puntos de vista: estudio serológico de los anticuerpos HLA y caracterización histológica del rechazo humoral. Para ello, hemos analizado una amplia cohorte de pacientes trasplantados con estudio de anticuerpos antiHLA pre y postrasplante determinados mediante tecnología Luminex. Los pacientes con anticuerpos dirigidos frente al donante detectados pretrasplante presentan una peor supervivencia del injerto y mayor riesgo de rechazo mediado por anticuerpos; y este riesgo sigue incrementado tanto si persiste como si no persiste el anticuerpo después del trasplante o aparece de novo. Por otro lado, hemos realizado el estudio de otros anticuerpos considerados clásicamente menos inmunogénicos y con poca relevancia en el campo del trasplante hasta la fecha, pero que las nuevas técnicas en fase sólida permiten identificar, como son los anticuerpos frente a los antígenos HLA DP. En nuestra experiencia, el 10% de los pacientes trasplantados presentan anticuerpos antiHLA-DP detectados por Luminex, tanto pre como postrasplante. La presencia de estos anticuerpos no parece modificar el impacto en la supervivencia del injerto. Desde el punto de vista histológico, hemos demostrado que el rechazo mediado por anticuerpos es un diagnóstico frecuente en las biopsias tardías de injerto renal realizadas por indicación según los criterios de la clasificación de Banff 2013, y confiere un peor pronóstico que otras categorías histológicas. Finalmente, hemos profundizado en el análisis de la categoría histológica de rechazo mediado por anticuerpos comparando la clasificación de Banff 2009 con la nueva definición de cambios mediados por anticuerpos de la clasificación de Banff 2013. Según nuestros resultados, la clasificación de Banff 2013 proporciona un diagnóstico más preciso del rechazo mediado por anticuerpos.Kidney transplantation is considered the treatment of choice for patients with end-stage renal disease. It is associated with improved survival, better quality of life and reduced costs when compared with dialysis. Throughout the years, the progress in immunosuppression, the improvement in surgical techniques and a better understanding of transplant immunology have produced an increase in both patient and graft survival short-term, notwithstanding in medium and long-term outcomes. Two major developments have taken place over the last decade: the development of new techniques to detect HLA antibodies, and the histological characterization of antibody-mediated rejection. The aim of this thesis has been to expand the knowledge of antibody-mediated rejection by addressing the issue from these two points of view: HLA antibody serological testing with new techniques and histological characterization of humoral rejection. To that end, we have analyzed a large cohort of transplant patients with pre and post-transplant anti-HLA antibodies determined by Luminex technologies. Patients with preformed donor specific antibodies show worse graft survival and greater risk of antibody-mediated rejection, regardless potential DSA clearing after transplantation. Furthermore, we evaluated the impact of typically less immunogenic antibodies believed to be less relevant in the transplant field thus far, such as HLA DP antibodies, albeit detectable by newer solid phase techniques. In our experience, 10% of transplant patients show HLA DP antibodies as detected by Luminex assay both pre and post-transplant. The presence of these antibodies does not seem to modify graft survival Histologically, we have shown that antibody-mediated rejection is a common diagnosis most often seen in late kidney graft biopsies according to the Banff 2013 classification criteria; antibody-mediated rejection also shows worse prognosis compared to other histological categories. Eventually, we have delved into the analysis of the antibody-mediated rejection category by comparing the Banff 2009 classification to the new antibody-mediated changes from Banff 2013. According to our results, Banff 2013 classification provides a more accurate diagnosis of antibody-mediated rejection