Comparación de las ecuaciones MDRD y de las antiguas ecuaciones CKD-EPI frente a las nuevas ecuaciones CKD-EPI en pacientes con trasplante renal cuando se emplea 51Cr-EDTA para medir el filtrado glomerular / Comparison of MDRD and the old CKD-EPI equations with the new CKD-EPI equations in kidney transplant patients when glomerular filtration rate is measured with 51Cr-EDTA

INTRODUCCIÓN: Para la estimación del filtrado glomerular renal (FG) en trasplantados renales se emplean las ecuaciones MDRD y CKD-EPI de 2009 que han mostrado diferencias importantes cuando se comparan con el FG medido con técnicas de referencia. OBJETIVO: Analizar el rendimiento de las ecuaciones MDRD, CKD-EPI de 2009 y de 2012 en 270 pacientes trasplantados renales de un año de evolución, comparando con el FG medido con aclaramiento plasmático de 51Cr-EDTA. RESULTADOS: El FG medido fue 43,0 ± 11,4 (18,2-79,4) mL/min/1,73 m2, con niveles de creatinina de 1,42 ± 0,46 (0,60-4,33) mg/dL y de cistatina C de 1,45 ± 0,53 (0,42-3,48) mg/L. El FG medido se correlacionó moderadamente con creatinina (r = -0,61; p < 0,001) y cistatina C (r = - 0,52; p < 0,001). Empleando técnicas de regresión lineal observamos que creatinina, cistatina C, sexo y edad solo explicaban el 52% de la varianza total del FG. Todas las ecuaciones sobrestimaron el FG, con sesgo medio de +11,1 mL/min/1,73 m2 para MDRD, +16,4 mL/min/1,73 m2 para CKD-EPI de 2009, +15 mL/min/1,73 m2 para CKD-EPI con cistatina C y +14,1 mL/min/1,73 m2 para CKD-EPI con creatinina y cistatina C de 2012. Las estimaciones con MDRD y CKD-EPI de 2009 se correlacionaron mejor con 51Cr-EDTA que CKD-EPI con creatinina y/o cistatina C. Las sobrestimaciones se correlacionaron negativamente con los niveles de creatinina y cistatina C, siendo más importantes para CKD-EPI con creatinina y/o cistatina C cuando el FG fue mayor de 60 mL/min/1,73 m2. CONCLUSIONES: Las ecuaciones CKD-EPI de 2012 con creatinina y/o cistatina C sobrestiman el FG de forma muy marcada en estadios 1 y 2 de la enfermedad renal crónica, por lo que en ellos sería recomendable emplear la ecuación MDRD. La técnica de referencia empleada para medir el FG parece tener una influencia muy importante en el sesgo de las ecuaciones

BACKGROUND: When estimating the glomerular filtration rate (GFR) in kidney transplant patients, significant differences have been found between MDRD and the 2009 CKD-EPI equations, and reference techniques. OBJECTIVE: To analyse and compare the performance of MDRD and the 2009 and 2012 CKD-EPI equations against 51Cr-EDTA plasma clearance in measuring GFR in 270 kidney transplant patients after one year. RESULTS: The mean measured GFR was 43.0 ± 11.4 (18.2-79.4) ml/min/1.73 m2, with creatinine levels of 1.42 ± 0.46 (0.60-4.33) mg/dl and cystatin C levels of 1.45 ± 0.53 (0.42-3.48) mg/l. This correlated moderately with creatinine (r = -0.61, P < .001) and cystatin C (r = -0.52, P < .001). Using linear regression techniques, it was found that creatinine, cystatin C, gender and age only explained 52% of GFR total variance. All equations overestimated GFR, with a mean bias of +11.1 ml/min/1.73 m2 for MDRD, + 16.4 ml/min/1.73 m2 for 2009-CKD-EPI, +15 ml/min/1.73m2 for CKD-EPI with cystatin C, and +14.1 ml/min/1.73 m2 for 2012-CKD-EPI with creatinine and cystatin C. eGFR by MDRD and the 2009 CKD-EPI equation correlated better with 51Cr-EDTA than CKD-EPI with creatinine and/or cystatin C. The overestimations were negatively correlated with creatinine and cystatin C levels, most significantly for CKD-EPI with creatinine and/or cystatin C when GFR was greater than 60 ml/min/1.73 m2. CONCLUSIONS: The 2012 CKD-EPI equations with creatinine and/or cystatin C significantly overestimate GFR in stage 1 and 2 chronic kidney disease. The MDRD equations is therefore recommended in these cases. The reference method used to measure GFR seems to heavily influence the bias of the equations

Comparison of MDRD and the old CKD-EPI equations with the new CKD-EPI equations in kidney transplant patients when glomerular filtration rate is measured with 51Cr-EDTA. / Comparación de las ecuaciones MDRD y de las antiguas ecuaciones CKD-EPI frente a las nuevas ecuaciones CKD-EPI en pacientes con trasplante renal cuando se emplea 51Cr-EDTA para medir el filtrado glomerular.

BACKGROUND: When estimating the glomerular filtration rate (GFR) in kidney transplant patients, significant differences have been found between MDRD and the 2009 CKD-EPI equations, and reference techniques. OBJECTIVE: To analyse and compare the performance of MDRD and the 2009 and 2012 CKD-EPI equations against 51Cr-EDTA plasma clearance in measuring GFR in 270 kidney transplant patients after one year. RESULTS: The mean measured GFR was 43.0±11.4 (18.2-79.4)ml/min/1.73m2, with creatinine levels of 1.42±0.46 (0.60-4.33)mg/dl and cystatin C levels of 1.45±0.53 (0.42-3.48)mg/l. This correlated moderately with creatinine (r=-0.61, P<.001) and cystatin C (r=-0.52, P<.001). Using linear regression techniques, it was found that creatinine, cystatin C, gender and age only explained 52% of GFR total variance. All equations overestimated GFR, with a mean bias of +11.1ml/min/1.73m2 for MDRD, +16.4ml/min/1.73m2 for 2009-CKD-EPI, +15ml/min/1.73m2 for CKD-EPI with cystatin C, and +14.1ml/min/1.73m2 for 2012-CKD-EPI with creatinine and cystatin C. eGFR by MDRD and the 2009 CKD-EPI equation correlated better with 51Cr-EDTA than CKD-EPI with creatinine and/or cystatin C. The overestimations were negatively correlated with creatinine and cystatin C levels, most significantly for CKD-EPI with creatinine and/or cystatin C when GFR was greater than 60ml/min/1.73m2. CONCLUSIONS: The 2012 CKD-EPI equations with creatinine and/or cystatin C significantly overestimate GFR in stage 1 and 2 chronic kidney disease. The MDRD equations is therefore recommended in these cases. The reference method used to measure GFR seems to heavily influence the bias of the equations.

Novedades introducidas por el nuevo Real Decreto legislativo 1090/2015 de ensayos clínicos con medicamentos en España / News introduced by the new Real Legislative Decree 1090/2015 of clinical trials with medicines in Spain

Introducción: La participación de España en ensayos clínicos es una prueba fehaciente de su desarrollo en I+D en el sector salud y de intentar seguir a la vanguardia en cuanto a investigación médica se refiere. El nuevo reglamento del Parlamento Europeo y del Consejo sobre ensayos clínicos de medicamentos de uso humano (Reglamento UE 536/2014, de 16 de abril) deroga la legislación hasta ahora vigente (Directiva 2001/20/CE, de 4 de abril) obligando a modificar el Real Decreto español (RD 223/2004, de 16 de febrero), desarrollando aquellos aspectos que se dejan en mano de la legislación nacional. Objetivo: Analizar las principales modificaciones introducidas por el nuevo RD en investigación clínica (RD 1090/2015, de 4 de diciembre) que regula los ensayos clínicos con medicamentos, los Comités de Ética de la Investigación con medicamentos (CEIm) y el Registro español de ensayos clínicos y compararlas respecto a la normativa anterior. Material y Métodos: Se revisaron los RD 1090/2015, de 4 de diciembre y 223/2004, de 16 de febrero y se compararon las diferencias más destacables entre ambas normativas. Resultados: El nuevo desarrollo normativo introduce novedades importantes. Se abre la opción para la unificación del análisis de las solicitudes, de manera que junto con la autorización del ensayo clínico emitida por la AEMPS, únicamente haga falta que un CEIm acreditado emita su dictamen positivo que será vinculante. Regula nuevas definiciones, como la de ensayo clínico de bajo nivel de intervención, sujeto a normas menos rigurosas. Diferencia entre Comité de ética de la investigación (CEI) y CEIm, estableciendo los requisitos adicionales para pasar de ser CEI a CEIm. Define investigación clínica sin ánimo comercial (en la que el promotor es una universidad, hospital, organización científica pública, organización sin ánimo de lucro, organización de pacientes o investigador individual sin participación de la industria farmacéutica). Abre la opción de contratar un ensayo clínico previamente a su autorización. Define las indemnizaciones por daños y cómo se lleva a cabo la evaluación de los ensayos clínicos. Incorpora la figura del representante legalmente designado para sujetos incapaces y menores. Estipula las condiciones en situaciones de urgencia, embarazadas y periodos de lactancia así como del consentimiento informado. La principal novedad es el expediente único del ensayo clínico con dos partes, una de documentación para la Unión Europea (parte I) y otra de documentación nacional (parte II). Todos los datos tienen que ser enviados a una base de datos y un portal web de la Unión Europea de acceso público. Conclusiones: La nueva normativa propone dar un importante impulso a la investigación clínica en España con medicamentos, simplificando las trabas administrativas y agilizando la realización de estudios multicéntricos simultáneos en toda Europa. Mejora la delimitación de responsabilidades de los agentes que participan, aumenta la seguridad de los sujetos del ensayo, y a la vez, incrementa la eficiencia en los procesos de evaluación y comunicación implicados

Introduction: The participation of Spain in clinical trials is a reliable proof of its development in I+D in the health sector and of trying to follow at the vanguard of medical research. The new Regulation of the European Parliament and of the Council on Clinical Trials on medicines for human use (EU Regulation 536/2014, 16th April) derogates the legislation currently in force (Directive 2001/20/EC, 4th April) and it obliges to modify the Spanish Royal Decree (RD 223/2004, 16th February) to develop those aspects that are left in the hands of national legislation. Objetives: To analyze the main changes introduced by the new RD in clinical research (RD 1090/2015, 4th December), which regulates clinical trials with medicines, the Committees on Ethics of Research with Medicines (CERm) and the Spanish Registry of Clinical Trials and to compare them with the previous legislation. Material and methods: RD 1090/2015, 4th December was analyzed against RD 223/2004, 16th February, and the most important differences between the two regulations were compared. Results: The new regulatory development introduces important innovations. It opens the option for the unification of the analysis of the applications, so that, together with the authorization of the clinical trial issued by the SAMHP, it is only necessary that an accredited CERm emits its positive opinion that it will be binding. It regulates new definitions, such as the low-level clinical trial, subject to less stringent standards. It differentiates between Research Ethics Committee (REC) and CERm, establishing additional requirements to move from being REC to CERm. It defines non-commercial clinical research (in which the sponsor is a university, hospital, public scientific organization, non-profit organization, patient organization or individual researcher without involvement of the pharmaceutical industry). It opens the option to contract a clinical trial prior to its authorization. It defines compensation for damages and how the evaluation of clinical trials is conducted. It incorporates the figure of the legally designated representative for incapable and minor subjects. It stipulates the conditions in situations of urgency, pregnant and periods of lactation as well as informed consent. The main novelty is the single dossier of the two-part clinical trial, one for European Union (Part I) and another one for National Documentation (Part II). All data must be sent to a database and a European public access web portal. Conclusions: The new regulation proposes to give an important impulse to the clinical research in Spain with medicines, simplifying the administrative obstacles and speeding up the realization of multicentric studies simultaneously in all Europe. It improves the delimitation of the responsibilities of the agents involved, it increases the safety of the test subjects, and at the same time, it increases the efficiency in the evaluation and communication processes involved

Activating brown adipose tissue through exercise (ACTIBATE) in young adults: Rationale, design and methodology.

AIMS: The energy expenditure capacity of brown adipose tissue (BAT) makes it an attractive target as a therapy against obesity and type 2 diabetes. BAT activators namely catecholamines, natriuretic peptides and certain myokines, are secreted in response to exercise. ACTIBATE will determine the effect of exercise on BAT activity and mass measured by positron emission tomography/computed tomography (PET/CT, primary outcome) in young adults. ACTIBATE will also investigate the physiological consequences of activating BAT (secondary outcomes). METHODS: ACTIBATE will recruit 150 sedentary, healthy, young adults (50% women) aged 18-25 years. Eligible participants will be randomly assigned to a non-exercise group (n ≈ 50) or one of two exercise groups (n=50 each). Participants in the exercise groups will perform aerobic and strength training 3-4 days/week at a heart rate equivalent to 60% of heart rate reserve (HRres), and at 50% of 1 repetition maximum (RM) for the moderate-intensity group, and at 80% of HRres and 70% RM for the vigorous-intensity group. Laboratory measures completed at baseline and 6 months include BAT activity and mass, resting energy expenditure, meal and cold-induced thermogenesis, body temperature regulation and shivering threshold, body composition and cardiovascular disease risk factors. We will also obtain biopsies from abdominal subcutaneous white adipose tissue and skeletal muscle to analyse the expression of genes encoding proteins involved in the thermogenic machinery. DISCUSSION: Findings from ACTIBATE will have significant implications for our understanding of exercise and its protective effects against the development of type 2 diabetes, obesity and related metabolic diseases. ClinicalTrials.gov ID: NCT02365129.

Two-phase scintigraphy with technetium 99m-sestamibi in patients with hyperparathyroidism due to chronic renal failure.

BACKGROUND: The objective of the current study was to study different functional and anatomic features of the hyperplastic gland and clinical and biochemical characteristics of renal hyperparathyroidism (HPT) patients and their relationship with the scintigraphic detection of parathyroid glands. METHODS: A retrospective study was performed of 40 patients with chronic renal failure (CRF) who underwent cervical surgery for HPT. Weight, histology, and localization of hyperplastic glands were recorded. Parathyroid cell proliferation was assessed by percentage of S-phase cells. Double-phase scintigraphy with technetium 99m-sestamibi and serum parathyroid intact hormone (PTHi), creatinine, calcium, and phosphate levels were performed. RESULTS: Detection of hyperplastic parathyroid glands by 99mTc-sestamibi scintigraphy was associated with the weight and inferior localization of the glands. The functionality of the glands as reflected in serum PTHi and phosphorus levels was associated with the number of glands detected. CONCLUSION: Double-phase 99mTc-sestamibi scintigraphy is of limited usefulness in patients with renal HPT. Detection of hyperplastic parathyroid glands in patients with CRF depends on the weight and inferior localization of the glands. Serum PTHi, phosphorus and creatine levels are associated with the number of glands detected by means of 99mTc-sestamibi scintigraphy.