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

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Estudio del daño renal inducido por la activación del sistema del complemento durante el fenómeno de isquemia reperfusión

Els avenços realitzats en els últims anys en les tècniques d'extracció i preservació dels òrgans trasplantats, així com en la medicació immunosupressora i l'avaluació de risc immunològic, han permès millorar la supervivència de l'empelt renal i del receptor a curt termini. Aquesta millora no es veu tan clarament reflectida a mitjà i llarg termini. Probablement, una de les causes d'això últim és la funció retardada de l'empelt, una forma de dany renal agut, que es presenta en un 20-50% dels receptors de donant cadàver i que empitjora el pronòstic dels ronyons trasplantats que la pateixen . En aquesta línia, la principal causa de funció retardada de l'empelt és el dany induït per la isquèmia-reperfusió, procés en part inherent a la tècnica del trasplantament renal, que es pot veure agreujat per múltiples factors com poden ser la situació del donant previ a la extracció de l'òrgan, la mateixa intervenció quirúrgica o per característiques del receptor. L'activació de el sistema del complement és un dels principals mecanismes involucrats en la fisiopatologia d'aquest fenomen. L'objectiu de la present tesi és aprofundir en el coneixement de el dany induït per l'activació del sistema del complement en el fenomen d'isquèmia-reperfusió, en l'àmbit del trasplantament renal. Per això, hem dissenyat tres estudis que abasten diferents aspectes clínics i etiopatogènics del dany pel complement en la isquèmia-reperfusió. Inicialment, vam analitzar l'impacte de la funció retardada de l'empelt, en una àmplia cohort de pacients trasplantats renals. Detectem pitjor supervivència de l'empelt i pitjor funció renal a l'any del trasplantament, en aquells pacients que van presentar funció retardada de l'empelt. D'altra banda, analitzem, la dinàmica de les concentracions solubles de el complex d'atac de membrana, producte de l'activació de la via final de el sistema del complement; també, examinem el patró histològic dels dipòsits del complex d'atac de membrana, C3d i el factor H. Aquesta anàlisi va ser realitzat en pacients trasplantats renals, amb i sense funció retardada de l'empelt, seguits de manera prospectiva. Vam trobar un augment rellevant tant dels nivells plasmàtics, com dels dipòsits histològics del complex d'atac de membrana, C3d i factor H, en aquells casos amb funció retardada de l'empelt. A més, vam detectar que una major concentració de nivells plasmàtics de complex d'atac de membrana es relaciona amb pitjor funció renal a 1 i 2 anys després de l'trasplantament. També vam desenvolupar un model d'hipòxia-reoxigenació, utilitzant cèl·lules tubulars proximals humanes (HK-2). Aquest model va revelar activació local de diferents components de sistema del complement, inclòs el complex d'atac de membrana, i els receptors de C5a (C5aR1 i C5L2), un altre producte final de el sistema del complement, poc estudiat en aquest àmbit. Finalment, avaluem l'expressió histològica de C5aR1 i C5L2, en biòpsies de pacients trasplantats renals amb funció retardada de l'empelt i un grup control. Aquesta anàlisi ens va mostrar, major expressió de C5aR1 a la membrana de les cèl·lules tubulars i de C5L2 en endoteli capil·lar peritubular en les biòpsies de pacients amb funció retardada de l'empelt, comparat amb els controls.Los avances realizados en los últimos años en las técnicas de extracción y preservación de los órganos trasplantados, así como en la medicación inmunosupresora y la evaluación del riesgo inmunológico, han permitido mejorar la supervivencia del injerto renal y del receptor a corto plazo. Esta mejoría no se ve tan claramente reflejada a medio y largo plazo. Probablemente, una de las causas de esto último es la función retrasada del injerto, una forma de daño renal agudo, que se presenta en un 20-50% de los receptores de donante fallecido y que empeora el pronóstico de los riñones trasplantados que la sufren. En esta línea, la principal causa de función retrasada del injerto es el daño inducido por la isquemia-reperfusión, proceso en parte inherente a la técnica del trasplante renal, que puede verse agravado por múltiples factores como pueden ser la situación del donante previo a la extracción del órgano, la propia intervención quirúrgica o por características del receptor. La activación del sistema del complemento es uno de los principales mecanismos involucrados en la fisiopatología de este fenómeno. El objetivo de la presente tesis es profundizar en el conocimiento del daño inducido por la activación del sistema del complemento en el fenómeno de isquemia-reperfusión, en el ámbito del trasplante renal. Para ello, hemos diseñado tres estudios que abarcan diferentes aspectos clínicos y etiopatogénicos del daño por el complemento en la isquemia-reperfusión. Inicialmente, analizamos el impacto de la función retrasada del injerto, en una amplia cohorte de pacientes trasplantados renales. Detectamos peor supervivencia del injerto y peor función renal al año del trasplante, en aquellos pacientes que presentaron función retrasada del injerto. Por otro lado, analizamos, la dinámica de las concentraciones solubles del complejo de ataque de membrana, producto de la activación de la vía final del sistema del complemento; también, examinamos el patrón histológico de los depósitos del complejo de ataque de membrana, C3d y el factor H. Este análisis fue realizado en pacientes trasplantados renales, con y sin función retrasada del injerto, seguidos de forma prospectiva. Encontramos un aumento relevante tanto de los niveles plasmáticos, como de los depósitos histológicos del complejo de ataque de membrana, C3d y factor H, en aquellos casos con función retrasada del injerto. Además, detectamos que una mayor concentración de niveles plasmáticos de complejo de ataque de membrana se relaciona con peor función renal a 1 y 2 años después del trasplante. También desarrollamos un modelo de hipoxia-reoxigenación, utilizando células tubulares proximales humanas (HK-2). Este modelo reveló activación local de diferentes componentes del sistema del complemento, incluido el complejo de ataque de membrana, y los receptores de C5a (C5aR1 y C5L2), otro producto final del sistema del complemento, poco estudiado en este ámbito. Finalmente, evaluamos la expresión histológica de C5aR1 y C5L2, en biopsias de pacientes trasplantados renales con función retrasada del injerto y un grupo control. Este análisis nos mostró, mayor expresión de C5aR1 en la membrana de las células tubulares y de C5L2 en endotelio de capilar peritubular en las biopsias de pacientes con función retrasada del injerto, comparado con los controles.The advances made during the last years in the extraction and preservation of the organs for transplantation, immunosuppressive medication, and the evaluation of immunological risk have improved patient and renal allograft survival. However, these improvements have had a limited effect on long-term survival. One of the reasons that negatively influence this long-term survival is the appearance of delayed graft function, a form of acute kidney damage, which occurs in 20-50% of deceased donor recipients and worsens the graft outcomes. The leading cause of delayed graft function is the damage induced by ischemia-reperfusion, a process inherent to the kidney transplantation process. The ischemia-reperfusion injury could be aggravating by different variables such as the donor's situation before organ retrieval or recipient characteristics. In the pathophysiology of this phenomenon, the activation of the complement system is highly relevant. This thesis's objective has been to expand our understanding of the damage induced by the activation of the complement system during ischemia-reperfusion injury in kidney transplantation. To this end, we designed three studies that evaluated different clinical and etiopathogenic aspects of the ischemia-reperfusion phenomenon. We initially assessed the impact of delayed graft function in a large cohort of kidney transplant patients. The development of delayed graft function was associated with worse graft survival and worse kidney function in the first year after transplantation. On the other hand, we analyze the dynamics of plasma levels of the membrane attack complex's soluble form, the final product from complement system activation in kidney transplant patients with and without delayed graft function. Additionally, we examined the histological pattern of the deposits of the membrane attack complex, C3d, and factor H in kidney biopsies from patients who were experiencing delayed graft function and controls with normal biopsies. We detected a relevant increase in plasma levels and histological deposits of the membrane attack complex, C3d, and factor H, in those patients with delayed graft function. A high concentration of membrane attack complex levels was related to worse kidney function at one and two years after transplantation. Finally, we developed a model of hypoxia-reoxygenation with human proximal tubular cells (HK-2). We demonstrated local activation of the complement system's different components, including the membrane attack complex, and the C5a receptors (C5aR1 and C5L2), another product of the complement system, scarcely studied in this area. Besides, we observed a higher expression of C5aR1 in the tubular cell membrane and C5L2 in the peritubular capillary endothelium, in biopsies of patients with delayed graft function, compared to controls

Frailty among chronic kidney disease patients on the kidney transplant waiting list : the sex-frailty paradox

Frailty is defined as decreased physiologic reserve and resistance to stressors that predisposes patients towards poor health results. Its prevalence in chronic kidney disease (CKD) patients who are kidney transplant (KT) candidates is high. Frailty is associated with a higher rate of complications and mortality after transplant. It is unknown whether frailty phenotype differs depending on sex in this population. This was a prospective longitudinal study of 455 KT candidates evaluated for frailty by physical frailty phenotype at the time of inclusion on the KT waiting list. Pre-frailty was defined as the presence of two criteria and frailty as three or more criteria. Univariate and multivariate analyses searched for associations of frailty status, frailty components and gender differences. Thirty percent of the total cohort resulted to be pre-frail (20%) or frail (10.3%), but disparities were observed between sexes, with 22.5% of men and 47.2% of women falling into one of these categories. Among frailty criteria, women presented with a higher percentage of exhaustion (39.6% versus 17%) and slowness (22.2% versus 9.6%) compared with men. Comorbidity burden was higher among frail men, whereas social factors were poorer between frail women. Disability was common among those patients who were frail, both men and women. Frailty is twice as frequent in advanced CKD women as men. Frailty criteria distribution and phenotype seem to differ among sexes, which might have implications in terms of specific and individualized interventions to improve their status before transplantation

Memorias. Encuentro de Experiencias en Inventarios y Monitoreo Biológico

Las discusiones temáticas alrededor de la consolidación del Inventario Nacional de Biodiversidad para Colombia y la Red de Monitoreo de Biodiversidad como una estrategia de largo plazo, sin duda temas complejos que requerirán de grandes esfuerzos, coordinación y generosidad institucional y personal, los podrá apreciar el lector a lo largo del presente documento, esperando que pueda entender también la importancia que tienen los resultados y la agenda propuesta si en el futuro queremos tomar decisiones con bases científicas

COVID-19-related mortality in kidney transplant and dialysis patients: Results of the ERACODA collaboration

Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 6 13 and 67 6 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3\u201330.2%] in kidney transplant and 25.0% (95% CI 20.2\u201330.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59\u20131.10, P \ubc 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n \ubc 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation <1 year before presentation (HR adjusted for sex, age and frailty 0.20, 95% CI 0.07\u20130.56, P < 0.01). Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients

Association of obesity with 3-month mortality in kidney failure patients with COVID-19

Background: In the general population with coronavirus disease 2019 (COVID-19), obesity is associated with an increased risk of mortality. Given the typically observed obesity paradox among patients on kidney function replacement therapy (KFRT), especially dialysis patients, we examined the association of obesity with mortality among dialysis patients or living with a kidney transplant with COVID-19. Methods: Data from the European Renal Association COVID-19 Database (ERACODA) were used. KFRT patients diagnosed with COVID-19 between 1 February 2020 and 31 January 2021 were included. The association of Quetelet's body mass index (BMI) (kg/m2), divided into: <18.5 (lean), 18.5-24.9 (normal weight), 25-29.9 (overweight), 30-34.9 (obese I) and ≥35 (obese II/III), with 3-month mortality was investigated using Cox proportional-hazards regression analyses. Results: In 3160 patients on KFRT (mean age: 65 years, male: 61%), 99 patients were lean, 1151 normal weight (reference), 1160 overweight, 525 obese I and 225 obese II/III. During follow-up of 3 months, 28, 20, 21, 23 and 27% of patients died in these categories, respectively. In the fully adjusted model, the hazard ratios (HRs) for 3-month mortality were 1.65 [95% confidence interval (CI): 1.10, 2.47], 1 (ref.), 1.07 (95% CI: 0.89, 1.28), 1.17 (95% CI: 0.93, 1.46) and 1.71 (95% CI: 1.27, 2.30), respectively. Results were similar among dialysis patients (N = 2343) and among those living with a kidney transplant (N = 817) (Pinteraction = 0.99), but differed by sex (Pinteraction = 0.019). In males, the HRs for the association of aforementioned BMI categories with 3-month mortality were 2.07 (95% CI: 1.22, 3.52), 1 (ref.), 0.97 (95% CI: 0.78. 1.21), 0.99 (95% CI: 0.74, 1.33) and 1.22 (95% CI: 0.78, 1.91), respectively, and in females corresponding HRs were 1.34 (95% CI: 0.70, 2.57), 1 (ref.), 1.31 (95% CI: 0.94, 1.85), 1.54 (95% CI: 1.05, 2.26) and 2.49 (95% CI: 1.62, 3.84), respectively. Conclusion: In KFRT patients with COVID-19, on dialysis or a kidney transplant, obesity is associated with an increased risk of mortality at 3 months. This is in contrast to the obesity paradox generally observed in dialysis patients. Additional studies are required to corroborate the sex difference in the association of obesity with mortality

Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy

© 2022, The Author(s).In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk

Clinical, Functional, and Mental Health Outcomes in Kidney Transplant Recipients 3 Months after a Diagnosis of COVID-19

Background. Kidney transplant patients are at high risk for coronavirus disease 2019 (COVID-19)-related mortality. However, limited data are available on longer-term clinical, functional, and mental health outcomes in patients who survive COVID-19. Methods. We analyzed data from adult kidney transplant patients in the European Renal Association COVID-19 Database who presented with COVID-19 between February 1, 2020, and January 31, 2021. Results. We included 912 patients with a mean age of 56.7 (±13.7) y. 26.4% were not hospitalized, 57.5% were hospitalized without need for intensive care unit (ICU) admission, and 16.1% were hospitalized and admitted to the ICU. At 3 mo follow-up survival was 82.3% overall, and 98.8%, 84.2%, and 49.0%, respectively, in each group. At 3 mo follow-up biopsy-proven acute rejection, need for renal replacement therapy, and graft failure occurred in the overall group in 0.8%, 2.6%, and 1.8% respectively, and in 2.1%, 10.6%, and 10.6% of ICU-admitted patients, respectively. Of the surviving patients, 83.3% and 94.4% reached their pre-COVID-19 physician-reported functional and mental health status, respectively, within 3 mo. Of patients who had not yet reached their prior functional and mental health status, their treating physicians expected that 79.6% and 80.0%, respectively, still would do so within the coming year. ICU admission was independently associated with a low likelihood to reach prior functional and mental health status. Conclusions. In kidney transplant recipients alive at 3-mo follow-up, clinical, physician-reported functional, and mental health recovery was good for both nonhospitalized and hospitalized patients. Recovery was, however, less favorable for patients who had been admitted to the ICU