Cost-effectiveness of omalizumab for the treatment of severe pediatric allergic asthma-Results of a real-life study in Spain.

BACKGROUND: Severe pediatric allergic asthma (SPAA) induces a huge economic burden in terms of direct, indirect, and intangible costs. The use of omalizumab for the treatment of these patients has produced a significant improvement in several clinical outcomes, but at the same time, the cost for the management of the disease has also increased. The aim of this report was to evaluate whether the use of omalizumab is cost-effective. METHODS: A sample of 426 children with SPAA from the ANCHORS (Asthma iN CHildren: Omalizumab in Real-life in Spain) study was used to calculate the incremental cost-effectiveness ratio (ICER) for the avoidance of moderate-to-severe exacerbations (MSE) and also for the improvement in childhood Asthma Control Test (c-ACT) or the Asthma Control Questionnaire (ACQ5). We retrospectively collected data on health encounters and drug consumption before and up to 6 years after the beginning of the treatment with omalizumab. RESULTS: The ICER per avoided MSE was €2107 after 1 year, and it consistently decreased to €656 in those followed up to 6 years. Similarly, the ICER for the minimally important difference in control tests showed a decrease from €2059 to €380 per each 0.5 points of improvement in ACQ5 and from €3141 to €2322 per each 3 points improvement in c-ACT, at years 1 and 6, respectively. CONCLUSION: The use of OMZ is a cost-effective option for most children with uncontrolled SPAA, especially those who have frequent exacerbations; the costs are progressively reduced in successive years of treatment.

Ultra-high performance liquid chromatography coupled to ion mobility quadrupole time-of-flight mass spectrometry for the identification of non-volatile compounds migrating from 'natural' dishes.

Although most new biomaterials for food industry applications are labelled '100% natural fabrication' and 'chemical-free', certain compounds may migrate from those materials to the food, compromising the organoleptic characteristics and safety of the product. In this work, the degree of compound migration from dishes made with four different biomaterials: bamboo, palm leaf, wood and wheat pulp was investigated. Migration tests were carried out using three food simulants, 10% ethanol (simulant A), 3% acetic acid (simulant B), and 95% ethanol (simulant D2). Unequivocal identification of non-intentionally added substances (NIAS) is challenging even when using high-resolution mass spectrometry techniques however, a total of 25 different non-volatile compounds from the migration tests were identified and quantified using Ultra-high performance liquid chromatography coupled to ion mobility quadrupole time-of-flight mass spectrometry (UPLC-IMS-MS). In the bamboo samples three oligomers, cyclic diethylene glycol adipate, 3,6,9,16,19,22-hexaoxabicyclo[22.3.1]-octacosa-1(28),24,26-triene-2,10,15,23-tetrone and 1,4,7,14,17,20-hexaoxacyclohexacosane-8,13,21,26-tetrone exceeded the specified limits of migration.

Analysis of potential migration compounds from silicone molds for food contact by SPME-GC-MS.

Four commercially available silicone cupcake molds have been studied. An evaluation of the post-cure treatment applied to the silicone molds was carried out and the loss of volatile organic compounds after cure treatment was quantified. The two higher quality molds showed losses at the 0.5% (w/w) (recommended by BfR standard), while the two lower quality molds exceeded this limit. The migration studies were carried out using Tenax® as a solid food simulant. The volatile compounds that migrate were identified and quantified using SPME-GC-MS. Up to fourteen silicone oligomers were quantified. When the molds were subjected to post-cure treatment, none of them exceeded the global migration of 10 mg/dm2; while those lower quality molds showed migrations higher than 10 mg/dm2, so their use in contact with food is not recommended.

How bilastine is used to treat allergic rhinitis and urticaria in children.

Management guidelines for allergic rhinitis and urticaria recommend oral second-generation antihistamines as first-line treatment. The efficacy and safety of bilastine, the newest nonsedating second-generation antihistamine, are well established in adolescents/adults with these allergic conditions. The bilastine development program for pediatric use (2-<12 years) followed EMA-authorized processes. Pharmacokinetic/pharmacodynamic simulation and modeling and a pharmacokinetic study were conducted to identify and confirm the pediatric dose (10 mg/day). A Phase III, multicenter, double-blind, randomized, placebo-controlled, parallel-group study was performed to confirm the safety of bilastine 10 mg/day in children. In this article, evidence is reviewed for use of bilastine in children with allergic rhinoconjunctivitis or urticaria. Several cases are presented which demonstrate its role in routine clinical practice.

Extremity Tourniquet Training at High Seas.

BACKGROUND: Future navy officers require unique training for emergency medical response in the isolated maritime environment. The authors issued a workshop on extremity bleeding control, using four different commercial extremity tourniquets onboard a training sail ship. The purposes were to assess participants' perceptions of this educational experience and evaluate self-application simplicity while navigating on high seas. METHODS: A descriptive observational study was conducted as part of a workshop issued to volunteer training officers. A post-workshop survey collected their perceptions about the workshops' content usefulness and adequacy, tourniquet safety, self-application simplicity, and device preference. Tourniquet preference was measured by frequency count while the rest of the studied variables on a one-to-ten Likert scale. Frequencies and percentages were calculated for the studied variables, and application simplicity means compared using the ANOVA test (p < 0.05). RESULTS: Fifty-one Spanish training naval officers, aged 20 or 21, perceived high sea workshop content's usefulness, adequacy, and safety level at 8.6/10, 8.7/10, and 7.5/10, respectively. As for application simplicity, CAT and SAM-XT were rated equally with a mean of 8.5, followed by SWAT (7.9) and RATS (6.9), this one statistically different from the rest (p < 0.01). Windlass types were preferred by 94%. CONCLUSIONS: The training sail ship's extremity bleeding control workshop was perceived as useful and its content adequate by the participating midshipmen. Windlass types were regarded as easier to apply than elastic counterparts. They were also preferred by nine out of every ten participants.

Omalizumab outcomes for up to 6 years in pediatric patients with severe persistent allergic asthma.

BACKGROUND: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date. METHODS: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients < 18 years and initiating omalizumab between 2006 and 2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared with the baseline period. RESULTS: Of the 484 patients included, 101 (20.9%) reached 6 years of treatment. The mean ± standard deviation number of exacerbations decreased during the first year of treatment (7.9 ± 6.6 to 1.1 ± 2.0, P < .001) and remained likewise for up to 6 years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. CONCLUSION: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma.

Phenolic Compounds Content and Genetic Diversity at Population Level across the Natural Distribution Range of Bearberry (Arctostaphylos uva-ursi, Ericaceae) in the Iberian Peninsula.

Bearberry (Arctostaphylos uva-ursi) is a medicinal plant traditionally employed for the treatment of urinary tract infections due to high contents of arbutin (hydroquinone ß-D-glucoside), which is now mainly used as a natural skin-whitening agent in cosmetics. Bearberry has also been proposed as a natural antioxidant additive due to the high contents of phenolic compounds in leaves. We studied the variation on phenolic compounds in 42 wild populations of bearberry, aiming to elucidate if intrinsic biological, climatic, and/or geographic factors affect phenolic contents across its natural distribution in the Iberian Peninsula. Bearberry leaves were collected during autumn over a three-year period (2014-2016) in populations across a latitude and altitude gradient. Methanolic extracts showed a wide range of variation in total phenols content, and different phenolic profiles regarding arbutin (levels of this major constituent varied from 87 to 232 mg/g dr wt), but also catechin and myricetin contents, which were affected by geographic and climatic factors. Moderate levels of variation on genome size-assessed by flow cytometry-and on two plastid DNA regions were also detected among populations. Genetic and cytogenetic differentiation of populations was weakly but significantly associated to phytochemical diversity. Elite bearberry genotypes with higher antioxidant capacity were subsequently identified.

Migration of volatile compounds from natural biomaterials and their safety evaluation as food contact materials.

The concern for environmental conservation is increasing, and a very important factor to consider is the search for alternatives to the use of plastics in the food packaging industry. A good option is the manufacture of containers of biodegradable materials, such as the so-called biomaterials made of vegetable fibre such as wheat, wood, bamboo or palm leaf pulp. The migration of compounds from food packaging can cause alterations in food safety and acceptability. Therefore, their control through studies of specific migration is definitely important in the food industry. Specific migration has been studied in two types of dishes (wheat pulp and wood) in contact with three liquid simulants (ethanol 10%, acetic acid 3% and ethanol 95%). The analysis of migration extracts have been carried out by solid-phase microextraction coupled to gas chromatography (SPME-GC-MS) in the most suitable working conditions. In addition, those identified compounds considered of interest according to existing legislation have been quantified in order to assess whether exceed or not the migration limits established for some of them. The results obtained show that the quantified compounds are well below the specific migration limits (SML) set by the legislation, thereby showing the safety in use of this type of biodegradable dishes.

Predicting the antioxidant capacity and total phenolic content of bearberry leaves by data fusion of UV-Vis spectroscopy and UHPLC/Q-TOF-MS.

The total phenolic content (TPC) and antioxidant capacity have been considered as important quality parameters for plant extracts. In this study, bearberry leaves were regarded as studied subject and a reliable method was established to predict the TPC and antioxidant capacity of bearberry leaves. Ultraviolet-visible spectrometry (UV-Vis) and ultra high pressure liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) were used to provide spectral fingerprinting and metabolomic profiling. The data obtained (separately and merged) were used to build partial least squares (PLS) regression model. The PLS model built by using ultraviolet-visible spectra provided a satisfactory prediction result. Mid-level data fusion using the scores significantly improved the performance of PLS regression model, the residual predictive deviations (RPDs) for TPC and α, α-diphenyl-ß-picrylhydrazyl (DPPH) were 6.258 and 6.699, respectively, showing an excellent predictive ability. This study proved the potential of combination of UV-Vis spectrometry and UHPLC/Q-TOF-MS in the prediction of TPC and antioxidant capacity of plant extracts.

Determination the set-off migration of ink in cardboard-cups used in coffee vending machines.

The set-off migration from printing inks can cause alterations in the safety and acceptability of food. Therefore, its control in the food industry is of special importance. The aim of this study was the determination of the migration of compounds coming from different types of cardboard-cups used in coffee vending machines. The volatile compounds present in cardboard-cups were studied and specific migration studies were carried out by solid phase microextraction with headspace coupled to gas chromatography (HS-SPME-GC-MS). The migration of compounds from the cardboard-cups manufacturing material, plastic coating (LDPE) and printing inks were identified and quantified. Those migrants listed in the Regulation No. 10/2011 presented values lower than the specific migration limit (SML), although a series of non-listed and non-authorized compounds were identified. From the results obtained the risk assessment of the vending cups from two different companies has been done.

Late Plasma Cell Depletion After Thymoglobulin Induction in Kidney Transplant Recipients.

OBJECTIVES: Induction therapy with rabbit antithymocyte globulin is frequently used in kidney transplant recipients and contributes to regulating the humoral alloantibody response. However, the effect of rabbit antithymocyte globulin on B-cell subpopulations, including plasma cells, has not been previously studied in humans in vivo. MATERIALS AND METHODS: We prospectively studied a cohort of 39 adult kidney transplant recipients. Twenty patients received rabbit antithymocyte globulin as induction therapy. Peripheral blood samples were obtained pretransplant and at 6 and 12 months posttransplant. T and B cells were acquired by flow cytometry. RESULTS: Total lymphocytes and CD3 and CD4 cells significantly decreased at 6 and 12 months only in patients who received rabbit antithymocyte globulin. In contrast, the CD19 population did not change after rabbit antithymocyte globulin induction. One-year circulating plasma cells remained significantly lower than pretransplant levels in patients who received rabbit antithymocyte globulin. We observed sig-nificant differences in plasma cell numbers at 12 months after transplant between patients who received rabbit antithymocyte globulin and those patients who did not receive it (median of 5 and interquartile range of 3-17 vs median of 25 and interquartile range of 12-35; P = .001). CONCLUSIONS: Rabbit antithymocyte globulin induction leads to a late reduction in the number of circulating plasma cells at 1 year after kidney transplant. This effect can contribute to down-regulation of the humoral alloantibody response.

Antioxidant and antimicrobial markers by UPLC®-ESI-Q-TOF-MSE of a new multilayer active packaging based on Arctostaphylos uva-ursi.

49 different non-volatile compounds were determined in Spanish Arctostaphylos uva-ursi leaves using UPLC®-ESI-Q-TOF with MSE technology. Both positive and negative electrospray ionization were applied. MarkerLynx® was proposed as a powerful tool to distinguish samples from eight wild populations of Spain by determining their non-volatile markers. Development of HRMS methods let to analysis of metabolites in plants. Antioxidant and antimicrobial capacities of different extracts were evaluated. Plant extract with the strongest antioxidant and simultaneous good antimicrobial capacity (Lierta) was chosen and incorporated in a multilayer packaging. Then, antioxidant capacity of the new packaging was evaluated and the efficient free radical scavenging properties were demonstrated.

Spanish traditional tomato. Effects of genotype, location and agronomic conditions on the nutritional quality and evaluation of consumer preferences.

Traditional tomatoes are highly valued for their organoleptic quality and cultural links with a territory. At present, strong competition has put these crops at risk, and it is necessary to differentiate the local cultivars and improve their nutritional value. This work focused on the nutritional study of four selected lines of a local tomato grown in two locations and in two agronomic conditions to nutritionally characterize the tomatoes and to study the effect of location and cultivation on nutritional parameters. Data on nutritional characterization revealed significant effects of location and treatment in most compounds. Tomatoes grown in traditional areas showed a significantly higher concentration of some phenolic acids and beta-carotene. Lycopene contents were not location dependent. The open field test showed significant differences in all the components. Regarding the best nutritional genotypes, all the components were dependent on lines, and significant differences were confirmed between them.

Resultados de supervivencia en cinco neoplasias malignas separados por una década en el Institut Català d'Oncologia / Survival results in five malignant neoplasms separated by a decade at Institut Català d'Oncologia, Spain

Fundamento y objetivo: Se presentan datos de supervivencia relativa (SR) (cociente entre la supervivencia observada y la esperada) a 5 años en las siguientes neoplasias: mama, pulmón, colorrectal (CCR), linfoma no Hodgkin de células grandes tipo B (LNHB) y mieloma múltiple (MM) tratados en el Institut Català d'Oncologia (ICO) en el período 2010-2011 y se comparan con los obtenidos en una cohorte especial histórica de los años 1998-1999. Material y métodos: Para el segundo estudio, se creó una base de datos donde se introdujeron 5.000 registros con datos de la historia clínica. Para el análisis de resultados se utilizó el paquete estadístico R®para la SR. Resultados: Las SR globales a 5 años del segundo período (2010-2011) fueron: CCR 67%, mama 93,6%, pulmón 28%, LNHB 68,3% y MM 61,7% y para el primero (1998-1999) fueron: CCR 61,8%, mama 88,8%, pulmón 23,1%, LNHB 67,7% y MM 43,4%. Conclusiones: Se registró una mejoría de la SR, de alrededor del 5%, en los 3 tumores sólidos, un incremento significativo en el MM y una estabilización en los LNHB (AU)

Background and objective: Five years' data relative survival (RS) is presented in 3 solid tumours: breast, colorectal (CRC) and lung and 2 haematologic neoplasms: large B cell lymphoma (NHL-B) and multiple myeloma (MM) treated at Institut Català d'Oncologia between 2010-2011 in comparison with the results obtained in a historical special cohort from 1998-1999. Material and methods: A database was created in a common safe and accessible repository. We have introduced more than 5,000 medical records. To analyse the results the statistical package R® was used for RS. Results: The overall RS at 5 years for 2010-2011 was: CRC 67%, breast 93.6%, lung 28%, NHL-B 68% and MM 62%, while for 1998-1999 is was: CRC 61.8%, breast 88.8%, lung 23.1%, NHL-B 67.7%, and MM 43.4%. Conclusions: Comparative results have shown a 5% overall improvement in RS for the 3 solid tumours, a significant increase in MM and a stabilisation in the NHL-B (AU)

Survival results in five malignant neoplasms separated by a decade at Institut Català d'Oncologia, Spain. / Resultados de supervivencia en cinco neoplasias malignas separados por una década en el Institut Català d'Oncologia.

BACKGROUND AND OBJECTIVE: Five years' data relative survival (RS) is presented in 3 solid tumours: breast, colorectal (CRC) and lung and 2 haematologic neoplasms: large B cell lymphoma (NHL-B) and multiple myeloma (MM) treated at Institut Català d'Oncologia between 2010-2011 in comparison with the results obtained in a historical special cohort from 1998-1999. MATERIAL AND METHODS: A database was created in a common safe and accessible repository. We have introduced more than 5,000 medical records. To analyse the results the statistical package R® was used for RS. RESULTS: The overall RS at 5 years for 2010-2011 was: CRC 67%, breast 93.6%, lung 28%, NHL-B 68% and MM 62%, while for 1998-1999 is was: CRC 61.8%, breast 88.8%, lung 23.1%, NHL-B 67.7%, and MM 43.4%. CONCLUSIONS: Comparative results have shown a 5% overall improvement in RS for the 3 solid tumours, a significant increase in MM and a stabilisation in the NHL-B.

Accumulation of De-Icing Salt and Leaching in Spanish Soils Surrounding Roadways.

The environmental implications of soil salinity caused by accumulation of de-icing salt and leaching in soils of northeastern Spain were examined. For this purpose, the concentrations of ions associated with diagnosing and managing this problem were evaluated from several measurements performed over one year along a road. This analysis demonstrated a higher concentration of soluble Na⁺ in the soil 3 m from a road in the northernmost part of the study area in February, which made the soil saline-sodic. Data from the rest of the study period (during the spring and summer) demonstrated that the de-icing salt moved to areas farther south by runoff water, which caused environmental impacts by modifying soil characteristics. These results suggest that leaching of Ca2+ and Mg2+ cations occurred faster in the studied systems in sodic soils. Leaching of these cations may affect plant yield, and results in environmental impacts within 3-30 m from the road. Awareness of this impact will be useful for developing future strategies for evaluating and reporting these complex relationships within Spain's transport system and environment.

Improving radiation oncology through clinical audits: Introducing the IROCA project.

As radiotherapy practice and processes become more complex, the need to assure quality control becomes ever greater. At present, no international consensus exists with regards to the optimal quality control indicators for radiotherapy; moreover, few clinical audits have been conducted in the field of radiotherapy. The present article describes the aims and current status of the international IROCA "Improving Radiation Oncology Through Clinical Audits" project. The project has several important aims, including the selection of key quality indicators, the design and implementation of an international audit, and the harmonization of key aspects of radiotherapy processes among participating institutions. The primary aim is to improve the processes that directly impact clinical outcomes for patients. The experience gained from this initiative may serve as the basis for an internationally accepted clinical audit model for radiotherapy.

Intermediate steroid withdrawal after renal transplantation and anti-HLA antibodies (HLA-Abs) development / Retirada intermedia de esteroides después del trasplante renal y desarrollo de anticuerpos anti-HLA (Ac-antiHLA)

Introduction: Steroid withdrawal in renal transplantation is desirable to avoid their adverse effects. However, by decreasing the immunosuppression, could lead to an increased risk for the development of HLA-Abs. Objective: Evaluate the relationship between steroid withdrawal and development of HLA-Abs in renal transplantation. Methods: We analyzed sera by Luminex from 182 kidney transplants performed from 1998 to 2011, before and two years after transplantation. All the patients had a pretransplant PRA (panel reactive of antibodies) <20% by complement-dependent cytotoxicity (CDC) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF). We compared a group of steroid withdrawal at 7 months (group-I; n=130) and another control with non-withdrawal (group-II; n=52). Results: 22 patients (16.9%) in group-I and 11 patients in group-II (21.1%) had HLA-Abs after two years (pNS). Despite excluding patients with PRA >20%, we detected HLA-Abs pretransplant by Luminex in 11.5% of patients in both groups, of which, 66.6%, versus 53% (p 0.058), developed new specificities, with a similar percentage of donor specific antibodies (DSA) in both groups (33.33% vs 36.36%), pNS. In the subgroup without pretransplant HLA-Abs (group-I; n=115, group-II; n=45), 6.08% developed de novo HLA-Abs, being DSA 3.4% (Group-I) versus 7.69% in group II with 3.84% DSA (pNS). Conclusions: Steroid withdrawal at 7 months of renal transplantation does not entail a higher risk in terms of HLA-Abs development in patients without pretransplant HLA-Abs and treatment with tacrolimus and MMF, although larger studies are needed to confirm these findings (AU)

Introducción: La retirada de esteroides en el trasplante renal es deseable por sus efectos adversos, sin embargo, al disminuir la inmunosupresión podría conllevar un riesgo superior para el desarrollo de Ac-anti-HLA. Objetivo: Evaluar la relación entre la retirada de esteroides y el desarrollo de Ac-anti-HLA en el trasplante renal. Métodos: Se evaluaron los sueros por Luminex de 182 trasplantados renales desde 1998 a 2011, antes y a los 2 años del trasplante. Todos tenían un panel reactivo frente a anticuerpos (PRA)<20% pretrasplante por citotoxicidad dependiente de complemento y mantuvieron la inmunosupresión con tacrolimús y micofenolato mofetilo (MMF). Comparamos un grupo de retirada de esteroides a los 7 meses (grupo I; n=130) y otro de no retirada (grupo II; n=52). Resultados: 22 pacientes (16,9%) en el grupo I y 11 pacientes en el grupo II (21,1%) presentaban Ac-anti-HLA a los 2 años (pNS). A pesar de excluir a los pacientes con PRA>20%, detectamos Ac-anti-HLA pretrasplante por Luminex en el 11,5% de los pacientes en ambos grupos, de los cuales, desarrollaron nuevas especificidades el 66,6% del grupo Iy el 53% en el grupo II (p 0,058), con un similar porcentaje de anticuerpos donante específicos (DSA) (33,3% vs. 36,36%), pNS. En el subgrupo sin Ac-anti-HLA pretrasplante (grupo I; n=115; grupo II; n=45), el 6,08% desarrollaron Ac-anti-HLA de novo, siendo DSA el 3,4% (grupo-I) vs. 7,69% con DSA en el 3,84% (grupo-II), pNS. Conclusiones: La retirada de esteroides a los 7 meses del trasplante renal no conlleva un riesgo superior en términos de desarrollo de Ac-anti-HLA en aquellos pacientes sin anticuerpos pretrasplante y en tratamiento con tacrolimús y MMF, aunque se requieren estudios más amplios para confirmar estos hallazgos (AU)

Assessment of Spanish Panel Reactive Antibody Calculator and Potential Usefulness.

BACKGROUND AND OBJECTIVES: The calculated panel reactive of antibodies (cPRAs) necessary for kidney donor-pair exchange and highly sensitized programs are estimated using different panel reactive antibody (PRA) calculators based on big enough samples in Eurotransplant (EUTR), United Network for Organ Sharing (UNOS), and Canadian Transplant Registry (CTR) websites. However, those calculators can vary depending on the ethnic they are applied. Here, we develop a PRA calculator used in the Spanish Program of Transplant Access for Highly Sensitized patients (PATHI) and validate it with EUTR, UNOS, and CTR calculators. METHODS: The anti-human leukocyte antigen (HLA) antibody profile of 42 sensitized patients on waiting list was defined, and cPRA was calculated with different PRA calculators. RESULTS: Despite different allelic frequencies derived from population differences in donor panel from each calculator, no differences in cPRA between the four calculators were observed. The PATHI calculator includes anti-DQA1 antibody profiles in cPRA calculation; however, no improvement in total cPRA calculation of highly sensitized patients was demonstrated. INTERPRETATION AND CONCLUSION: The PATHI calculator provides cPRA results comparable with those from EUTR, UNOS, and CTR calculators and serves as a tool to develop valid calculators in geographical and ethnic areas different from Europe, USA, and Canada.

Intermediate steroid withdrawal after renal transplantation and anti-HLA antibodies (HLA-Abs) development.

INTRODUCTION: Steroid withdrawal in renal transplantation is desirable to avoid their adverse effects. However, by decreasing the immunosuppression, could lead to an increased risk for the development of HLA-Abs. OBJECTIVE: Evaluate the relationship between steroid withdrawal and development of HLA-Abs in renal transplantation. METHODS: We analyzed sera by Luminex from 182 kidney transplants performed from 1998 to 2011, before and two years after transplantation. All the patients had a pretransplant PRA (panel reactive of antibodies) <20% by complement-dependent cytotoxicity (CDC) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF). We compared a group of steroid withdrawal at 7 months (group-I; n=130) and another control with non-withdrawal (group-II; n=52). RESULTS: 22 patients (16.9%) in group-I and 11 patients in group-II (21.1%) had HLA-Abs after two years (pNS). Despite excluding patients with PRA >20%, we detected HLA-Abs pretransplant by Luminex in 11.5% of patients in both groups, of which, 66.6%, versus 53% (p 0.058), developed new specificities, with a similar percentage of donor specific antibodies (DSA) in both groups (33.33% vs 36.36%), pNS. In the subgroup without pretransplant HLA-Abs (group-I; n=115, group-II; n=45), 6.08% developed de novo HLA-Abs, being DSA 3.4% (Group-I) versus 7.69% in group II with 3.84% DSA (pNS). CONCLUSIONS: Steroid withdrawal at 7 months of renal transplantation does not entail a higher risk in terms of HLA-Abs development in patients without pretransplant HLA-Abs and treatment with tacrolimus and MMF, although larger studies are needed to confirm these findings.