A Prospective Multicenter Trial to Evaluate Urinary Metabolomics for Non-invasive Detection of Renal Allograft Rejection (PARASOL): Study Protocol and Patient Recruitment

Kidney transplant rejection; Non-invasive test; Urinary metabolitesRechazo del trasplante renal; Prueba no invasiva; Metabolitos urinariosRebuig del trasplantament renal; Prova no invasiva; Metabòlits urinarisBackground: In an earlier monocentric study, we have developed a novel non-invasive test system for the prediction of renal allograft rejection, based on the detection of a specific urine metabolite constellation. To further validate our results in a large real-world patient cohort, we designed a multicentric observational prospective study (PARASOL) including six independent European transplant centers. This article describes the study protocol and characteristics of recruited better patients as subjects. Methods: Within the PARASOL study, urine samples were taken from renal transplant recipients when kidney biopsies were performed. According to the Banff classification, urine samples were assigned to a case group (renal allograft rejection), a control group (normal renal histology), or an additional group (kidney damage other than rejection). Results: Between June 2017 and March 2020, 972 transplant recipients were included in the trial (1,230 urine samples and matched biopsies, respectively). Overall, 237 samples (19.3%) were assigned to the case group, 541 (44.0%) to the control group, and 452 (36.7%) samples to the additional group. About 65.9% were obtained from male patients, the mean age of transplant recipients participating in the study was 53.7 ± 13.8 years. The most frequently used immunosuppressive drugs were tacrolimus (92.8%), mycophenolate mofetil (88.0%), and steroids (79.3%). Antihypertensives and antidiabetics were used in 88.0 and 27.4% of the patients, respectively. Approximately 20.9% of patients showed the presence of circulating donor-specific anti-HLA IgG antibodies at time of biopsy. Most of the samples (51.1%) were collected within the first 6 months after transplantation, 48.0% were protocol biopsies, followed by event-driven (43.6%), and follow-up biopsies (8.5%). Over time the proportion of biopsies classified into the categories Banff 4 (T-cell-mediated rejection [TCMR]) and Banff 1 (normal tissue) decreased whereas Banff 2 (antibody-mediated rejection [ABMR]) and Banff 5I (mild interstitial fibrosis and tubular atrophy) increased to 84.2 and 74.5%, respectively, after 4 years post transplantation. Patients with rejection showed worse kidney function than patients without rejection. Conclusion: The clinical characteristics of subjects recruited indicate a patient cohort typical for routine renal transplantation all over Europe. A typical shift from T-cellular early rejections episodes to later antibody mediated allograft damage over time after renal transplantation further strengthens the usefulness of our cohort for the evaluation of novel biomarkers for allograft damage.This study was sponsored by numares AG

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

Índex de Qualitat de la Prescripció Farmacèutica (IQF). Versió 2014

Índice de Calidad de la Prescripción Farmacéutica; IQSPrescription Quality Index; PQIÍndex de Qualitat de la Prescripció Farmacèutica; IQSL’Índex de Qualitat de Prescripció Farmacèutica (IQF) és una eina de la qual es dota al Catsalut per mesurar la dimensió científic-tècnica de la qualitat de la prescripció farmacèutica. L’objectiu final de l’IQF és fomentar l’ús dels fàrmacs més cost-efectius i reduir la variabilitat entre els professionals d’atenció primària i especialitzada de Catalunya. L’IQF és una eina de gestió que permet avaluar de manera quantitativa i qualitativa la prescripció farmacològica efectuada pels metges d’una organització. D’aquesta manera, permet identificar les millors pràctiques i establir el gold standard o patró d’or de la prescripció, així com realitzar comparacions (benchmarking). Proporciona informació per a la presa de decisions, permet fixar els objectius de millora i és una eina d’implantació de polítiques sanitàries mitjançant la seva introducció en els contractes de gestió.El Índice de Calidad de Prescripción Farmacéutica (IQF) es una herramienta de la que se dota al CatSalut para medir la dimensión científico-técnica de la calidad de la prescripción farmacéutica. El objetivo final del IQF es fomentar el uso de los fármacos mas coste-efectivos y reducir la variabilidad entre los profesionales de atención primaria y especializada de Cataluña. El IQF es una herramienta de gestión que permite evaluar de manera cuantitativa y cualitativa la prescripción farmacológica efectuada por los médicos de una organización. De esta forma, permite identificar las mejores prácticas y establecer el gold standard o patrón de oro de la prescripción, así como realizar comparacones (benchmarking). Proporciona información para la toma de decisiones, permite fijar los objetivos de mejora y es una herramienta de implantación de políticas sanitarias mediante su introducción en los contratos de gestión

Índex de Qualitat de la Prescripció Farmacèutica (IQF). Versió 2013

Índice de Calidad de la Prescripción Farmacéutica; IQSPrescription Quality Index; PQIÍndex de Qualitat de la Prescripció Farmacèutica; IQSL’Índex de Qualitat de Prescripció Farmacèutica (IQF) és una eina de la qual es dota al Catsalut per mesurar la dimensió científic-tècnica de la qualitat de la prescripció farmacèutica. L’objectiu final de l’IQF és fomentar l’ús dels fàrmacs més cost-efectius i reduir la variabilitat entre els professionals d’atenció primària i especialitzada de Catalunya. L’IQF és una eina de gestió que permet avaluar de manera quantitativa i qualitativa la prescripció farmacològica efectuada pels metges d’una organització. D’aquesta manera, permet identificar les millors pràctiques i establir el gold standard o patró d’or de la prescripció, així com realitzar comparacions (benchmarking). Proporciona informació per a la presa de decisions, permet fixar els objectius de millora i és una eina d’implantació de polítiques sanitàries mitjançant la seva introducció en els contractes de gestió.El Índice de Calidad de Prescripción Farmacéutica (IQF) es una herramienta de la que se dota al CatSalut para medir la dimensión científico-técnica de la calidad de la prescripción farmacéutica. El objetivo final del IQF es fomentar el uso de los fármacos mas coste-efectivos y reducir la variabilidad entre los profesionales de atención primaria y especializada de Cataluña. El IQF es una herramienta de gestión que permite evaluar de manera cuantitativa y cualitativa la prescripción farmacológica efectuada por los médicos de una organización. De esta forma, permite identificar las mejores prácticas y establecer el gold standard o patrón de oro de la prescripción, así como realizar comparacones (benchmarking). Proporciona información para la toma de decisiones, permite fijar los objetivos de mejora y es una herramienta de implantación de políticas sanitarias mediante su introducción en los contratos de gestión

Analysis of spontaneous resolution of cytomegalovirus replication after transplantation in CMV-seropositive patients with pretransplant CD8+IFNG+ response

This prospective study evaluates whether CMV-seropositive (R+) transplant patients with pretransplant CD8+IFNG+ T-cell response to cytomegalovirus (CMV) (CD8+IFNG+ response) can spontaneously clear the CMV viral load without requiring treatment. A total of 104 transplant patients (kidney/liver) with pretransplant CD8+IFNG+ response were evaluable. This response was determined using QuantiFERON-CMV assay. The incidence of CMV replication and disease was 45.2% (47/104) and 6.7% (7/104), respectively. Of the total patients, 77.9% (81/104) did not require antiviral treatment, either because they did not have CMV replication (n = 57) or because they had asymptomatic CMV replication that could be spontaneously cleared (n = 24). Both situations are likely related to the presence of CD8+IFNG+ response to CMV, which has a key role in controlling CMV infection. However, 22.1% of the patients (23/104) received antiviral treatment, although only 7 of them did so because they had symptomatic CMV replication. These patients developed symptoms in spite of having pretransplant CD8+IFNG+ response, thus suggesting that other immunological parameters might be involved, such as a dysfunctional CD4+ response or that they might have become QFNon-reactive due to the immunosuppression. In conclusion, around 80% of R+ patients with pretransplant CD8+IFNG+ response to CMV did not require antiviral treatment, although this percentage might be underestimated. Nevertheless, other strategies such as performing an additional CD8+IFNG+ response determination at posttransplant time might provide more reliable information regarding the patients who will be able to spontaneously clear the viremia

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Climatic and social factors behind the Spanish Mediterranean flood event chronologies from documentary sources (14th–20th centuries)

The Spanish Mediterranean river basin provides a good background for studying floods from documentary and bibliographical sources within the specialty of historical climatology. This study region's long history of human occupation and climatic conditions together determine a high risk of flooding. As a result, there exists an enormous amount of documentary heritage containing flood information. However, the heterogeneity of documentary sources and different approaches to classifying floods through historical documents can generate some biases and uncertainties about the quantity and quality of the available data. For this reason, this paper proposes a methodology for reconstructing historical floods based on cross-referencing documentary sources. This approach, together with additional archival work, has allowed us to increase the number of flood series for the Spanish Mediterranean coast by 17% and has generated a surprising increase of 233% in the number of flood cases detected. The data obtained have allowed us to analyze the variability of floods and their relationship with climatic and social factors from the fourteenth century to the present. Different climatic oscillations related to the Little Ice Age are detected between the 14th and 19th centuries. Additionally, we detected a strong influence of the defense infrastructures and urban growth, which explain the recent flood trends. However, the difficulty in analyzing the influence of social factors on long-term flood behavior invites us to reflect on the need for further work for emphasizing these issues.This work has been partially supported by the Spanish Ministry of Economy and Innovation (CGL2016-75996-R). SG-G acknowledges the support of the Spanish Ministry of Science, Innovation and Universities through “Juan de la Cierva-Incorporación” grant (IJCI-2016-29016). AA acknowledges the support of the Spanish Ministry of Economy and Innovation (HAR2017-82810-P). MB acknowledges the support of the Research Group of Generalitat de Catalunya “Paleogeoecologia, Riscs Naturals i Gestió Ambiental (PaleoRisk)” (2017SGR1106)

Comparative analysis of tools to predict rapid progression in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease and shows a wide phenotype. Only patients with rapid progression (RP) are included in clinical trials or are approved to receive disease-modifying drugs. This study aims at comparing different available predictive tools in ADPKD with the Mayo classification (MC) identification of rapid progressors based on high total kidney volume (TKV) according to age. A total of 164 ADPKD patients were recruited retrospectively from a single centre. The performance of diverse tools to identify RP defined as being in MC categories 1C-1E was assessed. A total of 118 patients were MC 1C-1E. The algorithm developed by the European Renal Association-European Dialysis and Transplant Association Working Group on Inherited Kidney Disorders/European Renal Best Practice had a low sensitivity in identifying MC 1C-1E. The sensitivity and specificity of TKV to predict RP depend on the cut-off used. A kidney length of >16.5 cm before age 45 years has high specificity but low sensitivity. Assessing the MC by ultrasonography had high levels of agreement with magnetic resonance imaging (MRI) data, especially for 1A, 1D and 1E. The estimated glomerular filtration rate (eGFR) decline was very sensitive but had low specificity. In contrast, the Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score was very specific but had poor sensitivity. Having hypertension before 35 years of age is a good clinical predictor of MC 1C-1E. Family history can be of help in suggesting RP, but by itself it lacks sufficient sensitivity and specificity. The MC by ultrasonography could be an option in hospitals with limited access to MRI as it performs well generally, and especially at the extremes of the MC, i.e. classes 1A, 1D and 1E. The eGFR decline is sensitive but not very specific when compared with the MC, whereas the PROPKD score is very specific but has low sensitivity. Integrating the different tools currently available to determine RP should facilitate the identification of rapid progressors among patients with ADPKD

Valvular heart disease and calcification in CKD: more common than appreciated

Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up &gt;50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10-20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications