Adrián Rodríguez

Health Research Institute of the Balearic Islands

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Inés Losada López

Health Research Institute of the Balearic Islands

F. Gráses

Research Institute of Health Sciences

Eugenia Cisneros‐Barroso

Health Research Institute of the Balearic Islands

Antonia Costa‐Bauzá

Research Institute of Health Sciences

Juan González‐Moreno

Hospital Son Llatzer

Tomás Ripoll‐Vera

Hospital Son Llatzer

Aina Gayà-Barroso

Health Research Institute of the Balearic Islands

Cristina Descals

Health Research Institute of the Balearic Islands

Mercedes García‐Gasalla

Health Research Institute of the Balearic Islands

Dolores Rodrigo

Instituto de Agroquímica y Tecnología de Alimentos

Cooperative Institutions

Health Research Institute of the Balearic Islands

Hospital Universitario Puerta de Hierro Majadahonda

Hospital Universitario Son Espases

Hospital Son Llatzer

Inserm

University College London

Instituto de Salud Carlos III

Assistance Publique – Hôpitaux de Paris

Centro de Investigación Biomédica en Red

Universitat de les Illes Balears

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Effect of sample time on urinary lithogenic risk indexes in healthy and stone-forming adults and children

BMC Urology (2018)

Adrián Rodríguez Concepción Sáez-Torres Concepcion Mir Paula Casasayas Núria Rodríguez

The diagnosis and follow-up of stone forming patients is usually performed by analysis of 24-h urine samples. However, crystallization risk varies throughout the day, being higher at night. The main objective of this study is to evaluate the urinary crystallization risk in adults and children by calculating risk indexes based on different collection periods.The study included 149 adults (82 healthy and 67 stone-formers) and 108 children (87 healthy and 21 stone-formers). 24-h urine was collected, divided into 12-h daytime sample (8 am to 8 pm), and 12-h overnight sample (8 pm to 8 am next morning). Solute concentrations, the calcium to citrate ratio (Ca/Cit), and the ion activity product of calcium oxalate (AP[CaOx]) and calcium phosphate (AP[CaP]) were calculated in each 12-h sample and in overall 24-h urine. Assessments were also related to stone type.Ca/Cit and AP(CaOx) were significantly higher in stone forming patients than in healthy subjects. The 12-h overnight samples had the highest values for both risk indexes, confirming a greater risk for crystallization at night. The AP(CaP) index was significantly higher in patients with pure hydroxyapatite stones than healthy controls, but was not significantly different between stone-formers overall and healthy controls.The calculation of risk indexes is a simple method that clinicians can use to estimate crystallization risk. For this purpose, the use of 12-h overnight urine may be a reliable alternative to 24-h collections.

Urinary stone

Urine sample

10.1186/s12894-018-0430-8

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Novel Colorimetric Determination of Phytate in Urine

Analytical Letters (2015)

Francisco Berga Adrián Rodríguez Antonia Costa‐Bauzá F. Gráses

Phytate is a natural substance present in urine and biological fluids that is associated with health benefits. Existing methods for the determination of phytate are not applicable to routine measurements in urine by clinical laboratories. This study describes a new method for measuring urinary phytate. Following its purification and preconcentration from urine by solid-phase extraction, phytate may be determined colorimetrically using Al(III)-lumogallion or Al(III)-pyrocatechol violet. Following preconcentration, the Al(III)-lumogallion assay was linear for 0 to 15 µM phytate with a limit of detection of 0.183 µM. In contrast, the Al(III)-pyrocatechol violet system was linear with phytate concentration from 0 to 10 µM and provided a limit of detection of 0.010 µM with a preconcentration procedure. Both methods are simple, rapid, accurate, reliable, and sensitive. Comparisons using synthetic and human urine samples with a reference Al(III)-xylenol orange method showed that the Al(III)-pyrocatechol violet assay is a good alternative for measuring urinary phytate.

Solid phase extraction

10.1080/00032719.2015.1060599

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Litiasis renal: avances en el estudio de inhibidores de la cristalización y en nuevas herramientas diagnósticas

Adrián Rodríguez

La litiasis renal es una enfermedad que consiste en la formacion de piedras en el interior de los rinones o de las vias urinarias. El diagnostico de alteraciones metabolicas en los pacientes litiasicos se realiza utilizando la muestra de orina de 24 horas, y el tratamiento de la patologia debe ir enfocado necesariamente al tipo de piedra o calculo que el paciente haya generado. El tratamiento con inhibidores de la cristalizacion, tales como el citrato, el fitato, o el magnesio, es un buen enfoque y ha demostrado ser eficaz. No obstante, el diagnostico de la enfermedad litiasica sigue presentando importantes problemas, y tambien creemos necesario seguir avanzando en el estudio de los inhibidores de la cristalizacion. A raiz de esta necesidad de seguir mejorando el conocimiento sobre inhibidores de la cristalizacion, y de mejorar las herramientas diagnosticas, se plantearon los objetivos de esta tesis, que ha derivado en 6 publicaciones y 4 patentes de invencion, todas ellas licenciadas a Devicare, S.L., con solicitud de PCT aprobada y extendidas a mas de 10 paises. El articulo original 1 describe el efecto inhibitorio que tienen las mezclas binarias de los inhibidores mas conocidos de la cristalizacion del oxalato calcico: magnesio, citrato y fitato. El estudio revela que la mezcla de fitato y magnesio produce un efecto sinergico en la inhibicion de la cristalizacion del oxalato calcico, mientras que en los otros dos casos (mezclas de magnesio y citrato, y de fitato y citrato) el efecto es puramente aditivo. El articulo original 2 describe por primera vez un inhibidor de la cristalizacion del acido urico: la teobromina. Esta dimetilxantina, presente en cantidades importantes en el cacao, retrasa de forma muy marcada la cristalizacion del acido urico, ademas de modificar la morfologia de los cristales de acido urico generados. Dado que las concentraciones de teobromina ensayadas en el trabajo estan dentro de los margenes que puede haber en orina, su uso podria ser de gran utilidad para los pacientes con litiasis renal urica. Asi, una vez visto el efecto de la teobromina en la cristalizacion del acido urico, nos propusimos poner a punto una metodologia analitica para determinar la concentracion de teobromina en orina de forma sencilla. El articulo original 3 describe dicho metodo, basado en cromatografia liquida de alta resolucion, acoplado a un sistema de deteccion ultravioleta. Una vez validado este metodo, se utilizo para demostrar la relacion existente entre el consumo de alimentos que provengan del cacao, y la excrecion urinaria de teobromina, en 80 ninos sanos. A pesar de que este metodo es muy sencillo y util, unicamente nos permitia analizar la concentracion de teobromina. Sin embargo, nos parecio relevante poder disponer de un metodo mas amplio, que posibilitara analizar otras metilxantinas (como la cafeina o la teofilina), algunos metabolitos de dichas sustancias, y otras sustancias como la hipoxantina, la xantina y el acido urico, que tambien estan implicados que la enfermedad litiasica. Asi, en el articulo original 4, utilizando un sistema de cromatografia liquida de alta resolucion acoplado a un espectrometro de masas de alta resolucion, desarrollamos un metodo rapido que nos permite analizar doce compuestos en orina en un periodo de tiempo de 10 minutos. Otro de los aspectos en los que se ha pretendido avanzar durante el desarrollo de esta tesis es en el de las mejoras de las herramientas diagnosticas. En especial, hemos centrado los esfuerzos en mejorar la medida del pH urinario, un parametro esencial en la enfermedad litiasica, y en el tipo de muestra de orina utilizada para realizar las medidas del riesgo litogeno urinario. Asi, en el articulo original 5 se comparan dos metodos de medicion de pH: la tira reactiva, ampliamente utilizada por enfermos litiasicos y en hospitales, y un nuevo dispositivo patentado por el Laboratorio de Investigacion en Litiasis Renal. Ambos metodos se comparan con el metodo de referencia: el pH-metro con electrodo de vidrio. El estudio muestra que la tira reactiva no tiene la precision suficiente para poder ser utilizada en el ambito de la litiasis renal, mientras que el nuevo dispositivo es preciso, facil de usar, y puede ser utilizado por el propio paciente en su casa. Para acabar, en el articulo original 6, se recogieron muestras de orina de 24 horas, que es la de eleccion para el diagnostico de alteraciones metabolicas urinarias, en 257 ninos y adultos, tanto sanos como litiasicos. Dicha muestra de orina se recogio en dos botes: 12 horas diurna (desde las 8:00 hasta las 20:00) en el primer bote, y 12 horas nocturna (desde las 20:00 hasta las 8:00 del dia siguiente) en el segundo. Se estudio el riesgo litogeno urinario mediante la utilizacion de diferentes formulas de riesgo, en ambas muestras de orina, asi como en el total de las 24 horas. Los resultados demuestran que las formulas de riesgo dan valores mas elevados para los pacientes litiasicos que para el grupo control, y ademas se observa que la orina nocturna tiene los valores de riesgo litogeno mas elevados, tanto en ninos como en adultos. De este modo, la orina de 12 horas nocturna puede ser una alternativa a la orina de 24 horas para el estudio del riesgo de cristalizacion en el paciente litiasico.

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Response to the letter: Comment on “Care bundle for the prevention of peripheral venous catheter blood stream infections at a secondary care university hospital: Implementation and results”

Infection Disease & Health (2023)

Yolanda Lladó Maura Magdalena Lucía Berga Figuerola M. José Rodríguez Moreno Verónica Lluch Garvi Elisabet E. Soler Felsner

Blood stream

Central venous catheter

Venous blood

Secondary Prevention

10.1016/j.idh.2023.07.003

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Effectiveness of a Multidisciplinary COPD Respiratory Unit (MUCOPD). A retrospective study.

05.02 - Monitoring airway disease (2024)

Elisabet Serra Amer Adrián Rodríguez J M Barros Rodríguez Salvador Pons Vives Antonia Fuster Gomila

10.1183/13993003.congress-2024.pa1240

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Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca

Orphanet Journal of Rare Diseases (2023)

Eugenia Cisneros‐Barroso Farida Gorram María Antonia Ribot-Sansó Flora Alarcon Grégory Nuel

Abstract Background Variant transthyretin amyloidosis (A-ATTRv) is an autosomal dominant disease caused by a range of TTR gene variants which entail great phenotypical heterogeneity and penetrance. In Majorca, the A-ATTRv caused by the V30M gene variant (A-ATTRV30M) is the most common. Since asymptomatic carriers are at risk of developing the disease, estimating age of onset is vital for proper management and follow-up. Thus, the aim of this study was to estimate age-related penetrance in ATTRV30M variant carriers from Majorca. Methods The disease risk among carriers from ATTRV30M families from Majorca was estimated by Non-parametric survival estimation. Factors potentially involved in the disease expression, namely gender and parent of origin were also analysed. Results A total of 48 heterozygous ATTRV30M families (147 affected patients and 123 were asymptomatic carriers) were included in the analysis. Penetrance progressively increased from 6% at 30 years to 75% at 90 years of age. In contrast to other European populations, we observe a similar risk for both males and females, and no difference of risk according to the parent of origin. Conclusions In this first study assessing the age-related penetrance of ATTRV30M variant in Majorcan families, no effect of gender or parent of origin was observed. These findings will be helpful for improving management and follow-up of TTR variant carrier individuals.

Human genetics

10.1186/s13023-023-02865-5

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Validating the usefulness of Sudoscan in ATTRv: a single centre experience

Neurological Sciences (2024)

Elena Moreno-Moraleda Juan González‐Moreno Eugenia Cisneros‐Barroso María Antonia Ribot-Sansó Tomás Ripoll‐Vera

Asymptomatic carrier

Sudomotor

10.1007/s10072-024-07311-3

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MO119COMPUTER-DERIVED SOFTWARE IN CLINICAL PRACTICE: RESULTS FROM A SHORT-TERM FOLLOW-UP ACCORDING TO KIDNEY STONE COMPOSITION IN KIDNEY STONE FORMERS

Nephrology Dialysis Transplantation (2021)

Tamara da Silva Cunha Adrián Rodríguez Pietro Manuel Ferraro

Abstract Background and Aims Urinary supersaturation (SS) contributes to stone formation, and its assessment in stone formers may be helpful in clinical practice. Several computer programs are available for SS calculation, including EQUIL2, JESS and Lithorisk1. The aim of this study was to evaluate changes in SS in 24-hour urine in patients with known stone composition before and after about three months of regular treatment. Method Patients who submitted their stone/s for composition analysis and had provided an adequate 24-hour urine collection (creatinine 15-20 mg/kg/24-hour) before and around 90 days under regular treatment were included. Stone composition was defined using morphoconstitutional and infrared spectroscopy. The treatment was initiated in accordance with specific guidelines, and included dietary advices and medications2. SS for calcium oxalate (CaOx), calcium phosphate (CaP) and uric acid (UA) using EQUIL2, JESS and Lithorisk were calculated at baseline and after about 90 days on treatment. Continuous variables were reported as means (SD) while categorical variables were reported as frequencies and percentages. Baseline and follow-up SS urine values were compared using the Wilcoxon signed-rank test. 3D graphs were plotted using mean SS values of CaOx, CaP and UA obtained from each program before and after treatment, dividing the stones into 4 groups1: calcium oxalate monohydrate (COM), calcium oxalate dihydrate (COD), calcium phosphate (CaP), and uric acid (UA). Ethical Committee approval was obtained. Results 105 patients (61 men, 58%) were followed and provided 24h urine collection. Of these, 101 (96%) were recurrent patients. The mean (SD) follow-up was 94 (14) days. 48 (46%) of all calculi were made of CaOx, either COM or COD, 36 (34%) of UA, and 21 (20%) of CaP. A significant reduction in SS values during treatment was observed in patients with COM (p<0.05) , COD (p<0.001), and UA stones (p<0.001) with all programs. The reduction in SS values over time in patients with CaP stones was not significant (Table 1). Figure 1 shows 3D plots with SS before and after treatment into 4 groups of stone formers. Conclusion EQUIL2, JESS and Lithorisk are suitable software currently used for clinical and research purposes. SS values calculated by EQUIL2, JESS and Lithorisk during follow-up showed a significant reduction among COM, COD and UA stone formers. CaP stone formers did not show significant changes in SS over time.

Kidney stone disease

10.1093/ndt/gfab107.008

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Citations (1)

Thick-Film Electrochemical Detectors for Poly(dimethylsiloxane)-based Microchip Capillary Electrophoresis

Electroanalysis (2002)

Joseph Wang Martin Pumera Madhu Prakash Chatrathi Adrián Rodríguez Scott D. Spillman

A new poly(dimethylsiloxane) (PDMS)-based microchip capillary electrophoresis (CE) device, with a thick-film electrochemical detector, is described. The end-column design relies on screen-printing the amperometric carbon working electrode on the base plate of a PDMS microchip (opposite to the exit of the microchannel). Since the channel depth and electrode height are quite similar, this is a flow-onto/flow-by hybrid arrangement. The influence of relevant experimental variables, such as the separation and detection potentials, is reported along with the attractive analytical performance. Flat baselines and extremely low noise levels are observed even at high separation fields (approaching 700 V/cm), reflecting the effective electrical isolation of the detector. The resulting detection limits (150 nM for epinephrine and 280 nM for catechol) compare favorably with those obtained by other PDMS-based electrochemical detectors. Such coupling of low-cost and versatile PDMS chips and thick-film electrochemical detectors holds great promise for high-volume production of disposable microfluidic analytical devices.

Amperometry

Microchannel

10.1002/1521-4109(200210)14:18<1251::aid-elan1251>3.0.co;2-g

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Citations (49)

Efficacy of Mixtures of Magnesium, Citrate and Phytate as Calcium Oxalate Crystallization Inhibitors in Urine

The Journal of Urology (2015)

F. Gráses Adrián Rodríguez Antonia Costa‐Bauzá

The main aim of the current study was to evaluate the effectiveness of mixtures of magnesium, citrate and phytate as calcium oxalate crystallization inhibitors.A turbidimetric assay in synthetic urine was performed to obtain induction times for calcium oxalate crystallization in the absence and presence of different mixtures of inhibitors. The morphology of calcium oxalate crystals in the absence or presence of inhibitors and mixtures of the inhibitors was evaluated in 2 crystallization experiments at low and high calcium oxalate supersaturation. The crystals formed were examined using scanning electron microscopy.Examination of crystallization induction times revealed clear inhibitory effects of magnesium, citrate and phytate on calcium oxalate crystallization, supporting usefulness in the treatment and prevention of calcium oxalate nephrolithiasis. Significant synergistic effects between magnesium and phytate were observed. Scanning electron microscopy images revealed that phytate is a powerful crystal growth inhibitor of calcium oxalate, totally preventing the formation of trihydrate and monohydrate. In addition to crystallization inhibition capacity, citrate and magnesium avoided calcium oxalate crystallization by decreasing its supersaturation.The synergistic effect between magnesium and phytate on calcium oxalate crystallization suggests that a combination of these 2 compounds may be highly useful as antilithiasis therapy.

Supersaturation

10.1016/j.juro.2015.03.099

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Citations (47)