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..

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

Strategies to reengage patients lost to follow up in HIV care in high income countries, a scoping review

Background: Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90-90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. Methods: A scoping review was done following Arksey & O'Malley's methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. Results: Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. Conclusions: This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Nueva variante en el gen COL4A3: etiología de un síndrome de Alport tipo 2 en varón de 38 años con sospecha de nefritis hereditaria

Los pacientes con síndrome de Alport experimentan una pérdida progresiva de la función renal, pérdida auditiva neurosensorial y anomalías oculares. Está causado por mutaciones en los genes COL4A5 (herencia ligada al cromosoma X), COL4A3 y COL4A4 (herencia autosómica dominante o recesiva), que codifican respectivamente las cadenas α3, α4 y α5 del colágeno tipo IV. En ausencia de tratamiento, el cuadro clínico progresa desde hematuria microscópica hacia proteinuria, insuficiencia renal progresiva y enfermedad renal terminal. En la actualidad, el trasplante renal supone el único tratamiento eficaz. Las pruebas genéticas de secuenciación masiva son el método de elección para el diagnóstico de esta patología

Recommendations for the use of everolimus in de novo kidney transplantation: false beliefs, myths and realities

The immunosuppressive combination most commonly used in de novo kidney transplantation comprises a calcineurin inhibitor (CI), tacrolimus, a mycophenolic acid derivative and steroids. The evidence which underlies this practice is based in the Symphony trial with controlled follow-up of one year, in which no comparator group included the combination CI-mTOR inhibitor. Different high-quality clinical trials support the use of everolimus as a standard immunosuppressive drug associated with reduced exposure of a CI in kidney transplantation. This combination could improve health related outcomes in kidney transplantation recipients. The present recommendations constitute an attempt to summarise the scientific evidence supporting this practice, discuss false beliefs, myths and facts, and offer specific guidelines for safe use, avoiding complications

A novel variant in the COL4A3 gene: etiology of Alport syndrome type 2 in a 38-year-old male with suspected hereditary kidney disease

Patients with Alport syndrome develop progressive kidney function deterioration, sensorineural hearing loss, and ocular abnormalities. This condition is caused by mutations in COL4A5 (X-linked inheritance), COL4A3 and COL4A4 (autosomal dominant or recessive inheritance), and encoding type IV collagen α3, α4, and α5, respectively. If left untreated, clinical symptoms progress from microscopic hematuria to proteinuria, progressive kidney failure, and end-stage kidney disease. At present, kidney transplantation is the only effective approach. Next-generation sequencing is the method of choice for the diagnosis of this condition

Survival and quality of life in elderly patients in conservative management

Introduction: Conservative Management (CM) has become a therapeutic option in Advanced Chronic Kidney Disease in the elderly. However, there is a lack of evidence about prognosis of these patients in terms of survival and health related quality of life (HRQoL). Objective: Establish predictive variables associated with mortality and analyse HRQoL in CM patients. Patients and methods: Prospective cohort study. An assessment of renal function parameters and a comprehensive geriatric assessment were made, including: analysis of comorbidity, functional, cognitive, fragility, nutritional, social and HRQoL status. Results: 82 patients with a mean age of 84 years and significant pluripathology were studied: 56% had history of vascular event and Charlson >8. The mortality rate was 23/1000 patients per month, with a homogeneous mortality rate after 6 months.Survival differed significantly depending on whether they presented with a previous vascular event (36.7 vs. 14.8; p = 0.028), Charlson score ≥ 10 (42 vs. 17; p = 0.002), functional status (48.4 vs. 19; p = 0.002) and fragility (27 vs. 10; p = 0.05). Mortality predictors included eGFR and proteinuria, the presence of previous vascular events, Charlson comorbidity score, malnutrition-inflammation parameters (albumin and MNA score), degree of dependency, physical HRQoL and increase of PTH level. The presence of previous vascular event, comorbidity, decreased albumin and elevated PTH were independent predictors of mortality. HRQoL remained stable over time and no significant worsening occurred during treatment. Conclusions: Having knowledge of the factors associated with mortality and HRQoL assessment can be a useful tool to helping decision making during CM. Previous vascular events, comorbidity, decreased albumin and increased PTH were independent predictors of mortality. Resumen: Introducción: El tratamiento renal conservador (TRC) se ha convertido en una opción terapéutica en la enfermedad renal crónica avanzada en ancianos. Se sabe poco sobre la evolución pronóstica de estos pacientes en términos de supervivencia y calidad de vida relacionada con la salud (CVRS). Objetivo: Establecer variables predictivas de mortalidad y analizar la CVRS en los pacientes en TRC. Pacientes y métodos: Estudio de cohortes prospectivo. Se realizó una valoración de parámetros de función renal y evaluación geriátrica integral: análisis de comorbilidad, situación funcional, cognitiva, fragilidad, nutricional, social y CVRS. Resultados: Se evaluaron 82 pacientes, con una edad media de 84 años e importante pluripatología: el 56% tenía antecedentes de evento vascular y Charlson > 8. La tasa de mortalidad fue de 23/1.000 pacientes-mes, con un ritmo de mortalidad homogéneo a partir de los 6 meses.La supervivencia difirió significativamente si presentaban evento vascular previo (36,7 vs. 14,8; p = 0,028), Charlson ≥ 10 (42 vs. 17; p = 0,002), grado de dependencia (48,4 vs. 19; p = 0,002) y fragilidad (27 vs. 10; p = 0,05).Fueron predictores de mortalidad: eFG y proteinuria, presencia de evento vascular previo, comorbilidad de Charlson, parámetros de malnutrición-inflamación (albúmina y puntuación MNA), grado de dependencia, CVRS física y aumento de PTH. La presencia de evento vascular previo, comorbilidad, albúmina descendida y elevación de PTH fueron predictores independientes de mortalidad. La CVRS se mantuvo estable y no se produjo empeoramiento significativo durante el tratamiento. Conclusiones: El conocimiento de los factores asociados con mortalidad y la evaluación de la CVRS puede ser útil como herramienta en la toma de decisiones en TRC. La presencia de evento vascular previo, comorbilidad, albúmina disminuida y el aumento de PTH fueron predictores independientes de mortalidad. Keywords: Conservative management, Survival, Elderly, Advanced chronic kidney disease, Palabras clave: Manejo conservador, Supervivencia, Ancianos, Enfermedad renal crónica avanzad

Supervivencia y calidad de vida en pacientes ancianos en tratamiento renal conservador

Resumen: Introducción: El tratamiento renal conservador (TRC) se ha convertido en una opción terapéutica en la enfermedad renal crónica avanzada en ancianos. Se sabe poco sobre la evolución pronóstica de estos pacientes en términos de supervivencia y calidad de vida relacionada con la salud (CVRS). Objetivo: Establecer variables predictivas de mortalidad y analizar la CVRS en los pacientes en TRC. Pacientes y métodos: Estudio de cohortes prospectivo. Se realizó una valoración de parámetros de función renal y evaluación geriátrica integral: análisis de comorbilidad, situación funcional, cognitiva, fragilidad, nutricional, social y CVRS. Resultados: Se evaluaron 82 pacientes, con una edad media de 84 años e importante pluripatología: el 56% tenía antecedentes de evento vascular y Charlson > 8. La tasa de mortalidad fue de 23/1.000 pacientes-mes, con un ritmo de mortalidad homogéneo a partir de los 6 meses.La supervivencia difirió significativamente si presentaban evento vascular previo (36,7 vs. 14,8; p = 0,028), Charlson ≥ 10 (42 vs. 17; p = 0,002), grado de dependencia (48,4 vs. 19; p = 0,002) y fragilidad (27 vs. 10; p = 0,05).Fueron predictores de mortalidad: eFG y proteinuria, presencia de evento vascular previo, comorbilidad de Charlson, parámetros de malnutrición-inflamación (albúmina y puntuación MNA), grado de dependencia, CVRS física y aumento de PTH. La presencia de evento vascular previo, comorbilidad, albúmina descendida y elevación de PTH fueron predictores independientes de mortalidad. La CVRS se mantuvo estable y no se produjo empeoramiento significativo durante el tratamiento. Conclusiones: El conocimiento de los factores asociados con mortalidad y la evaluación de la CVRS puede ser útil como herramienta en la toma de decisiones en TRC. La presencia de evento vascular previo, comorbilidad, albúmina disminuida y el aumento de PTH fueron predictores independientes de mortalidad. Abstract: Introduction: Conservative Management (CM) has become a therapeutic option in Advanced Chronic Kidney Disease in the elderly. However, there is a lack of evidence about prognosis of these patients in terms of survival and health related quality of life (HRQoL). Objective: Establish predictive variables associated with mortality and analyse HRQoL in CM patients. Patients and methods: Prospective cohort study. An assessment of renal function parameters and a comprehensive geriatric assessment were made, including: analysis of comorbidity, functional, cognitive, fragility, nutritional, social and HRQoL status. Results: 82 patients with a mean age of 84 years and significant pluripathology were studied: 56% had history of vascular event and Charlson > 8. The mortality rate was 23/1,000 patients per month, with a homogeneous mortality rate after 6 months.Survival differed significantly depending on whether they presented with a previous vascular event (36.7 vs. 14.8; p = 0.028), Charlson score ≥ 10 (42 vs. 17; p = 0.002), functional status (48.4 vs. 19; p = 0.002) and fragility (27 vs. 10; p = 0.05).Mortality predictors included eGFR and proteinuria, the presence of previous vascular events, Charlson comorbidity score, malnutrition-inflammation parameters (albumin and MNA score), degree of dependency, physical HRQoL and increase of PTH level. The presence of previous vascular event, comorbidity, decreased albumin and elevated PTH were independent predictors of mortality. HRQoL remained stable over time and no significant worsening occurred during treatment. Conclusions: Having knowledge of the factors associated with mortality and HRQoL assessment can be a useful tool to helping decision making during CM. Previous vascular events, comorbidity, decreased albumin and increased PTH were independent predictors of mortality. Palabras clave: Manejo conservador, Supervivencia, Ancianos, Enfermedad renal crónica avanzada, Keywords: Conservative management, Survival, Elderly, Advanced chronic kidney diseas

The use of lymphocyte-depleting antibodies in specific populations of kidney transplant recipients: a systematic review and meta-analysis

Background: Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic review aims to reevaluate, based on actual studies, the effects of different antibody preparations when used in specific KTR subgroups. Methods: We searched MEDLINE and CENTRAL and selected randomized controlled trials (RCT) and observational studies looking at different antibody preparations used as induction in KTR. Comparisons were categorized into different KTR subgroups: standard, high risk of rejection, high risk of delayed graft function (DGF), living donor, and elderly KTR. Two authors independently assessed the risk of bias. Results: Thirty-seven RCT and 99 observational studies were finally included. Compared to anti-interleukin-2-receptor antibodies (IL2RA), anti-thymocyte globulin (ATG) reduced the risk of acute rejection at two years in standard KTR (RR 0.74, 95%CI 0.61?0.89) and high risk of rejection KTR (RR 0.55, 95%CI 0.43?0.72), but without decreasing the risk of graft loss. We did not find significant differences comparing ATG vs. alemtuzumab or different ATG dosages in any KTR group. Conclusions: Despite many studies carried out on induction treatment in KTR, their heterogeneity and short follow-up preclude definitive conclusions to determine the optimal induction therapy. Compared with IL2RA, ATG reduced rejection in standard-risk, highly sensitized, and living donor graft recipients, but not in high DGF risk or elderly recipients. More studies are needed to demonstrate beneficial effects in other KTR subgroups and overall patient and graft survival