Influence of magnesium supplementation on oxidative stress, inflammation and vascular dysfunction associated to chronic kidney disease: in vivo and in vitro studies

Las enfermedades cardiovasculares (ECV) se mantienen como la principal causa de muerte en todo el mundo, superando incluso las debidas a todos los tumores combinados. En particular, la ECV es la principal causa de muerte en enfermos con alteraciones del metabolismo mineral, como son los pacientes con enfermedad renal crónica (ERC). La integridad funcional y estructural de la vasculatura es crítica en el mantenimiento de la homeostasis cardiovascular. La disfunción vascular aparece como el denominador común que conecta a ésta con los factores de riesgo cardiovascular y algunas patologías como la diabetes y el Síndrome Metabólico (SMet). El estrés oxidativo (EO) y la inflamación son procesos que invariablemente se asocian con las diferentes fases de la disfunción vascular. La sobreproducción de especies reactivas de oxígeno (EROs) contribuyen al deterioro vascular alterando el tono y el crecimiento vascular, además aumenta la regulación de mediadores proinflamatorios, como NF-κB. Mientras el aumento de marcadores inflamatorias juega un papel clave en la formación de lesiones vasculares junto con la inducción de EO, que a su vez potencia el proceso inflamatorio. De hecho, el EO y la inflamación son características comunes de la ERC. Los pacientes con ERC tienen sistemas antioxidantes gravemente deteriorados y suelen sufrir inflamación crónica, que empeoran progresivamente con el grado de insuficiencia renal. Las alteraciones en el metabolismo mineral presentes en la ERC pueden ser también un estímulo adicional en la respuesta inflamatoria y en el aumento de producción de EROs. Además, en los últimos años se viene abordando la posibilidad de considerar como posibles factores de riesgo cardiovascular algunos parámetros del metabolismo mineral (Fósforo (P), Magnesio (Mg2+), Factor de crecimiento fibroblástico 23 (FGF23) /Klotho y vitamina D (Vit D)). El conocimiento de las moléculas y las rutas esenciales en la preservación de la integridad y función de la vasculatura debe proporcionar la base para el descubrimiento de dianas terapéuticas eficaces para el tratamiento de la disfunción vascular. Nuestra hipótesis de trabajo establece que puede existir una asociación entre algunas alteraciones del metabolismo mineral, relacionadas con los niveles de P, Mg2+, FGF23/Klotho, Vit D, y el inicio y progresión de la disfunción vascular. Asimismo, pensamos que una intervención dietética rica en Mg2+ puede modular favorablemente estos parámetros del metabolismo mineral y, por tanto, resultar en un efecto protector frente a la disfunción vascular. El trabajo de investigación fue desarrollado en dos bloques. En el primer bloque, con el fin de evaluar del efecto del Mg2+ en la inflamación y el EO en la ERC, se realizó un estudio in vitro de células del músculo liso vascular (CMLV) cultivadas en P para promover EO e inflamación. Se estudiaron 3 grupos experimentales: un grupo control con niveles normales de P (0,9 mM) y Mg2+ (0,8 mM), un grupo con alto P (AP) (3,3 mM) y Mg2+ normal, y un grupo AP con adición de Mg2+ (1,6 mM) (AP+Mg2+). Además, se realizó un estudio in vivo en un modelo de rata Wistar con nefrectomía 5/6 (Nx5/6) para inducir la ERC donde fueron alimentados con una dieta alta en P (1,2%) que contenía un 0,1% de Mg2+ (Nx-Mg2+0,1%) o con una dieta suplementada con 0,6% de Mg2+ (Nx-Mg2+0,6%); usando como controles Wistar operadas de forma simulada que recibieron 0,1% de Mg2+. En el segundo bloque se evaluó el efecto del suplemento de Mg2+ dietético sobre el EO, la inflamación y la disfunción vascular en un modelo de rata de SMet (cepa Zucker) con ERC (Nx5/6). Los animales nefrectomizados fueron con un moderado contenido en P (0,9%) y con un contenido de Mg2+ 0,1% (SMet+Nx- Mg2+0,1%) o de 0,6% (SMet+Nx-Mg2+0,6%). Del mismo modo, se utilizaron de control ratas Zucker operadas de forma simulada que recibieron 0,1% de Mg2+. En el primer bloque, los resultados in vitro de las CMLV cultivadas en un medio proinflamatorio con alto P, se observó un aumento de la producción de EROs, incremento de la expresión de citoquinas y activación de la señalización NF-κB. La incubación con Mg2+ inhibió el aumento de la producción de EROs y de citoquinas, así como la activación de NF-κB. In vivo, las ratas Nx alimentadas con una dieta normal de Mg2+ (0,1%) mostraron una respuesta inflamatoria sistémica evidenciada por la elevación en plasma de las citoquinas proinflamatorias, y de la actividad de la glutatión peroxidasa (GPx), un marcador de EO. También se observó un aumento de la expresión de estas citoquinas en el tejido aórtico. Por el contrario, el suplemento dietético de Mg2+ (0,6%) previno en gran medida el EO y la actividad proinflamatoria. En cuanto al segundo bloque, el modelo in vivo de SMet-ERC, en comparación con los controles, el grupo SMet+Nx-Mg2+0,1% mostró un aumento significativo de los biomarcadores de EO e inflamación (peroxidación lipídica y expresión aórtica de citoquinas) y de los niveles de endotelina-1 (ET-1), una disminución del óxido nítrico (NO) y un empeoramiento de la uremia y de la patología asociada al SMet, como la hipertensión, glucosa y un perfil lipídico anormal. Además, la evaluación proteómica reveló cambios relacionados principalmente con el metabolismo lipídico y en marcadores de ECV. Por el contrario, en el grupo MetS+Nx- Mg2+0,6%, estos parámetros se mantuvieron en gran medida similares a los controles. En conclusión, el suplemento con Mg2+ redujo la inflamación y el EO, ejerciendo un efecto directo sobre las células vasculares. Además, el suplemento dietético con Mg2+ no solo redujo la inflamación y el EO asociados a la ERC, sino que mejoró la función vascular. En conjunto, estos hallazgos apoyan un posible efecto beneficioso del suplemento de Mg2+ en el manejo clínico de los pacientes con ECV y ERC.Cardiovascular diseases (CVD) remain the leading cause of death worldwide, even exceeding those due to all tumors combined. In particular, CVD is the leading cause of death in patients with alterations in mineral metabolism, such as patients with chronic kidney disease (CKD). The functional and structural integrity of the vasculature is critical in the maintenance of cardiovascular homeostasis. Vascular dysfunction appears as the common denominator that connects this with cardiovascular risk factors and some pathologies such as diabetes and metabolic syndrome (MetS). Oxidative stress (OS) and inflammation are processes that are invariably associated with the different phases of vascular dysfunction. Overproduction of reactive oxygen species (ROS) contributes to vascular deterioration by altering vascular tone and growth, in addition upregulation of proinflammatory mediators, such as NF- κB. While the increase in inflammatory markers plays a key role in the formation of vascular lesions along with the induction of OS, which in turn potentiates the inflammatory process. Indeed, OS and inflammation are common features of CKD. Patients with CKD have severely impaired antioxidant systems and often suffer from chronic inflammation, which progressively worsen with the degree of renal failure. The alterations in mineral metabolism present in CKD may also be an additional stimulus in the inflammatory response and in the increased production of ROS. Furthermore, in recent years some parameters of mineral metabolism (phosphorus (P), magnesium (Mg2+), fibroblast growth factor 23 (FGF23)/Klotho and vitamin D (Vit D)) have been considered as possible cardiovascular risk factors. Knowledge of the molecules and pathways essential in preserving the integrity and function of the vasculature should provide the basis for the discovery of effective therapeutic targets for the treatment of vascular dysfunction. Our hypothesis states that there may be an association between some alterations in mineral metabolism, related to P, Mg2+, FGF23/Klotho, Vit D levels, and the onset and progression of vascular dysfunction. Likewise, we believe that a dietary intervention rich in Mg2+ may favorably modulate these parameters of mineral metabolism and, therefore, result in a protective effect against vascular dysfunction. The research work was developed in two sections. In the first section, in order to evaluate the effect of Mg2+ on inflammation and OS in CKD, an in vitro study of vascular smooth muscle cells (VSMC) cultured in P to promote OS and inflammation was performed. Three experimental groups were studied: a control group with normal P (0.9 mM) and Mg2+ (0.8 mM) levels, a high P (AP) (3.3 mM) and normal Mg2+ group, and an AP group with addition of Mg2+ (1.6 mM) (AP+Mg2+). In addition, an in vivo study was performed in a Wistar rat model with 5/6 nephrectomy (Nx5/6) to induce CKD where they were fed a high P diet (1.2%) containing 0.1% Mg2+ (Nx-Mg2+0.1%) or a diet supplemented with 0.6% Mg2+ (Nx-Mg2+0.6%); using sham-operated Wistar receiving 0.1% Mg2+ as controls. In the second section, the effect of dietary Mg2+ supplementation on OS, inflammation and vascular dysfunction was evaluated in a rat model of MetS (Zucker strain) with CKD (Nx5/6). Nephrectomized animals were moderately P (0.9%) and Mg2+ 0.1% (SMet+Nx-Mg2+0.1%) or 0.6% (SMet+Nx-Mg2+0.6%). Similarly, sham-operated Zucker rats receiving 0.1% Mg2+ were used as controls. In the first section, in vitro results of VSMCs cultured in proinflammatory medium with high P, increased production of ROS, increased cytokine expression, and activation of NF-κB signaling were observed. Incubation with Mg2+ inhibited increased ROS and cytokine production, as well as NF-κB activation. In vivo, Nx rats fed a normal Mg2+ diet (0.1%) showed a systemic inflammatory response evidenced by elevation in plasma proinflammatory cytokines, and of glutathione peroxidase (GPx) activity, a marker of oxidative stress. Increased expression of these cytokines was also observed in aortic tissue. In contrast, dietary supplementation of Mg2+ (0.6%) largely prevented oxidative stress and proinflammatory activity. Regarding the second section, the in vivo MetS-CKD model, compared with controls, the MetS+Nx-Mg2+0.1% group showed a significant increase in biomarkers of oxidative stress and inflammation (lipid peroxidation and aortic cytokine expression) and endothelin-1 (ET-1) levels, a decrease in nitric oxide (NO), and a worsening of uremia and MetS-associated pathology, such as hypertension, glucose, and an abnormal lipid profile. In addition, proteomic evaluation revealed changes mainly related to lipid metabolism and in CVD markers. In contrast, in the MetS+Nx- Mg2+0.6% group, these parameters remained largely similar to controls. In conclusion, Mg2+ supplementation reduced inflammation and OS, exerting a direct effect on vascular cells. Furthermore, dietary supplementation with Mg2+ not only reduced CKD-associated inflammation and EO, but also improved vascular function. Taken together, these findings support a possible beneficial effect of Mg2+ supplementation in the clinical management of patients with CVD and CKD

Dietary Mg Supplementation Decreases Oxidative Stress, Inflammation, and Vascular Dysfunction in an Experimental Model of Metabolic Syndrome with Renal Failure

Background: Metabolic syndrome (MetS) and chronic kidney disease (CKD) are commonly associated with cardiovascular disease (CVD) and in these patients Mg concentration is usually decreased. This study evaluated whether a dietary Mg supplementation might attenuate vascular dysfunction through the modulation of oxidative stress and inflammation in concurrent MetS and CKD. Methods: A rat model of MetS (Zucker strain) with CKD (5/6 nephrectomy, Nx) was used. Nephrectomized animals were fed a normal 0.1%Mg (MetS+Nx+Mg 0.1%) or a supplemented 0.6%Mg (MetS+Nx+Mg0.6%) diet; Sham-operated rats with MetS receiving 0.1%Mg were used as controls. Results: As compared to controls, the MetS+Nx-Mg0.1% group showed a significant increase in oxidative stress and inflammation biomarkers (lipid peroxidation and aortic interleukin-1b and -6 expression) and Endothelin-1 levels, a decrease in nitric oxide and a worsening in uremia and MetS associated pathology as hypertension, and abnormal glucose and lipid profile. Moreover, proteomic evaluation revealed changes mainly related to lipid metabolism and CVD markers. By contrast, in the MetS+Nx+Mg0.6% group, these parameters remained largely similar to controls. Conclusion: In concurrent MetS and CKD, dietary Mg supplementation reduced inflammation and oxidative stress and improved vascular function.This research was funded by a Spanish government grant from the Programa Nacional I+D+I 2008–2011 from the MINECO-Instituto de Salud Carlos III (PI20/0660 and PI21/00654) with co-financing from European Funds (FEDER) and EUTOX and REDinREN from the ISCIII, Consejería de Salud (grants PI-0071-2021) from the Junta de Andalucía and Grant PY20_00773 from Consejería de Innovación, Ciencia y Empleo from the Junta de Andalucía. J.M.D.-T. hold a Sara Borrell contract by the Spanish Ministry of Science, Innovation and Universities, Carlos III Health Institute (ISCIII), co-funded by European Social Fund (European Social Fund-Investment in your future). Y.A. and J.R.M.-C. are senior researchers supported by the Nicolás Monardes Programme, Consejería de Salud-SAS (Junta de Andalucía)

Dietary Mg Supplementation Decreases Oxidative Stress, Inflammation, and Vascular Dysfunction in an Experimental Model of Metabolic Syndrome with Renal Failure

whether a dietary Mg supplementation might attenuate vascular dysfunction through the modulation of oxidative stress and inflammation in concurrent MetS and CKD. Methods: A rat model of MetS (Zucker strain) with CKD (5/6 nephrectomy, Nx) was used. Nephrectomized animals were fed a normal 0.1%Mg (MetS+Nx+Mg0.1%) or a supplemented 0.6%Mg (MetS+Nx+Mg0.6%) diet; Sham-operated rats with MetS receiving 0.1%Mg were used as controls. Results: As compared to controls, the MetS+Nx-Mg0.1% group showed a significant increase in oxidative stress and inflammation biomarkers (lipid peroxidation and aortic interleukin-1b and -6 expression) and Endothelin-1 levels, a decrease in nitric oxide and a worsening in uremia and MetS associated pathology as hypertension, and abnormal glucose and lipid profile. Moreover, proteomic evaluation revealed changes mainly related to lipid metabolism and CVD markers. By contrast, in the MetS+Nx+Mg0.6% group, these parameters remained largely similar to controls. Conclusion: In concurrent MetS and CKD, dietary Mg supplementation reduced inflammation and oxidative stress and improved vascular function

The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function

[Background] In chronic kidney disease (CKD) patients, increased levels of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality. The relationship between FGF23 and heart hypertrophy has been documented, however, it is not known whether FGF23 has an effect on vasculature. Vascular smooth muscle cells VSMCs may exhibit different phenotypes; our hypothesis is that FGF23 favours a switch from a contractile to synthetic phenotype that may cause vascular dysfunction. Our objective was to determine whether FGF23 may directly control a change in VSMC phenotype.[Methods] This study includes in vitro, in vivo and ex vivo experiments and evaluation of patients with CKD stages 2–3 studying a relationship between FGF23 and vascular dysfunction.[Results] In vitro studies show that high levels of FGF23, by acting on its specific receptor FGFR1 and Erk1/2, causes a change in the phenotype of VSMCs from contractile to synthetic. This change is mediated by a downregulation of miR-221/222, which augments the expression of MAP3K2 and PAK1. miR-221/222 transfections recovered the contractile phenotype of VSMCs. Infusion of recombinant FGF23 to rats increased vascular wall thickness, with VSMCs showing a synthetic phenotype with a reduction of miR-221 expression. Ex-vivo studies on aortic rings demonstrate also that high FGF23 increases arterial stiffening. In CKD 2–3 patients, elevation of FGF23 was associated with increased pulse wave velocity and reduced plasma levels of miR-221/222.[Conclusion] In VSMCs, high levels of FGF23, through the downregulation of miR-221/222, causes a change to a synthetic phenotype. This change in VSMCs increases arterial stiffening and impairs vascular function, which might ultimately worsen cardiovascular disease.This work was supported by a Spanish government grant from the Programa Nacional I+D+I 2013–2016 and Instituto de Salud Carlos III (ISCIII) grants PI18/0138 and PI21/0654 co-financing from European Funds (FEDER), Consejería de Salud (grants PI-0136 and PI-0169-2020) from the Junta de Andalucía, Framework Programme 7 Syskid UE grant FP7-241544, and EUTOX and REDinREN from the ISCIII. N.V. and J.M.D.-T. were supported by Consejería de Economía, Innovación, Ciencia y Empleo (grant CVI-7925) from the Junta de Andalucía. Y.A. and J.R.M.-C. are senior researchers supported by the Nicolás Monardes Programme, Consejería de Salud-Servicio Andaluz de Salud (Junta de Andalucía).Peer reviewe

Supplemental Material The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function

3 pages. -- Figure S1. Supplemental Material. Effects of anti-miR-221 and miR-222. -- Figure S1. Supplemental Material: A) Anti-miR-221 and B) anti-miR-222 transfection for 48 h decreased not significantly the expression of miR-221 and miR-222 in VSMC. -- Figure S2. Supplemental Material. Recombinant Klotho administration did not modify the expression of contractile markers of VSMC. -- Figure S3. Histological quantifications in thoracic aortas of rats of synthetic markers of VSMC.Peer reviewe

Magnesium supplementation reduces inflammation in rats with induced chronic kidney disease

Background Inflammation is a common feature in chronic kidney disease (CKD) that appears specifically associated with cardiovascular derangements in CKD patients. Observational studies have revealed a link between low Mg levels and inflammation. In this study, we hypothesize that Mg might have a modulatory effect on the inflammation induced under the uraemic milieu. Methods In vivo studies were performed in a 5/6 nephrectomized rat model of CKD. Furthermore, a possible direct effect of Mg was addressed through in vitro studies with vascular smooth muscle cells (VSMCs). Results Uraemic rats fed a normal (0.1%) Mg diet showed a systemic inflammatory response evidenced by the elevation in plasma of the pro‐inflammatory cytokines TNF‐α, IL‐1β and IL‐6, and GPx activity, a marker of oxidative stress. Importantly, an increased expression of these cytokines in the aortic tissue was also observed. In contrast, a dietary Mg supplementation (0.6%) greatly prevented the oxidative stress and the pro‐inflammatory response. In vitro, in VSMCs cultured in a pro‐inflammatory high phosphate medium, incubation with Mg 1.6 mM inhibited the increase in the production of ROS, the rise in the expression of TNF‐α, IL‐1β, IL‐6 and IL‐8 and the activation of NF‐κB signalling that was observed in cells incubated with a normal (0.8 mM) Mg. Conclusion Mg supplementation reduced inflammation associated with CKD, exerting a direct effect on vascular cells. These findings support a possible beneficial effect of Mg supplementation along the clinical management of CKD patients

Eficacia de las inyecciones intrarticulares de ácido hialurónico para el tratamiento de la artrosis de rodilla: resultados de una serie de casos tratados en una Unidad del Dolor

Objective: To evaluate the results of treatment of knee osteoarthritis with a single intra-articular injection of hyaluronic acid in terms of pain reduction, joint function improvement and duration of effects. Method: Patients with clinical and radiological diagnosis of osteoarthritis at different stages of evolution in one or both knees were treated at the Pain Unit of a tertiary hospital. Sociodemographic and clinical characteristics provided by the patient following the usual clinical practice were prospectively collected. Pain at rest, walking, up and down stairs, morning stiffness, time walking as well as time/quality sleep were recorded pre and post-treatment. At post-treatment visit the degree and duration of improvement experienced, as well as the investigator assessment were also recorded. The treatment consisted of a single intra-articular injection of hyaluronic acid, with the possibility of a booster. Results: A total of 29 patients (52 knees) were included. Both knees were treated in 23 of them (n = 46) and only one knee in the remaining 6. The 92.3 % were osteoarthritic joints with an evolution > 12 months, with clinical grade 4-5 in 61.6 % (n = 32) and radiological grade III-IV of Kellgren & Lawrence in 67.7 % (n = 35), making 55.8 % of cases were classified as severe by the investigators. There was a significant improvement in all parameters of pain and function considered (p 12 meses, con grado clínico 4-5 en el 61,6 % de las rodillas tratadas (n = 32) y grado radiológico III-IV de Kellgren y Lawrence en el 67,7 % (n = 35), por lo que un 55,8 % de los casos fueron calificados como severos por los investigadores. Hubo una mejoría significativa en todos los parámetros de dolor y funcionalidad considerados (p < 0,001). El tiempo caminando se incrementó en más del 100 % y el 67,3 % de los pacientes definieron su calidad de sueño como normal, frente al 38,5 % inicial. La mejoría fue valorada por el investigador como buena o muy buena en el 73,1 % de los casos. Conclusiones: Nuestro trabajo confirma la eficacia de una única inyección de ácido hialurónico para reducir la sintomatología en pacientes con gonartrosis en diferentes grados de severidad, con resultados que se mantienen entre 6 y 12 meses y son especialmente significativos en aquellos con artrosis leve y moderada

Magnesium supplementation reduces inflammation in rats with induced chronic kidney disease.

Inflammation is a common feature in chronic kidney disease (CKD) that appears specifically associated with cardiovascular derangements in CKD patients. Observational studies have revealed a link between low Mg levels and inflammation. In this study, we hypothesize that Mg might have a modulatory effect on the inflammation induced under the uraemic milieu. In vivo studies were performed in a 5/6 nephrectomized rat model of CKD. Furthermore, a possible direct effect of Mg was addressed through in vitro studies with vascular smooth muscle cells (VSMCs). Uraemic rats fed a normal (0.1%) Mg diet showed a systemic inflammatory response evidenced by the elevation in plasma of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6, and GPx activity, a marker of oxidative stress. Importantly, an increased expression of these cytokines in the aortic tissue was also observed. In contrast, a dietary Mg supplementation (0.6%) greatly prevented the oxidative stress and the pro-inflammatory response. In vitro, in VSMCs cultured in a pro-inflammatory high phosphate medium, incubation with Mg 1.6 mM inhibited the increase in the production of ROS, the rise in the expression of TNF-α, IL-1β, IL-6 and IL-8 and the activation of NF-κB signalling that was observed in cells incubated with a normal (0.8 mM) Mg. Mg supplementation reduced inflammation associated with CKD, exerting a direct effect on vascular cells. These findings support a possible beneficial effect of Mg supplementation along the clinical management of CKD patients

Dietary Mg Supplementation Decreases Oxidative Stress, Inflammation, and Vascular Dysfunction in an Experimental Model of Metabolic Syndrome with Renal Failure

Background: Metabolic syndrome (MetS) and chronic kidney disease (CKD) are commonly associated with cardiovascular disease (CVD) and in these patients Mg concentration is usually decreased. This study evaluated whether a dietary Mg supplementation might attenuate vascular dysfunction through the modulation of oxidative stress and inflammation in concurrent MetS and CKD. Methods: A rat model of MetS (Zucker strain) with CKD (5/6 nephrectomy, Nx) was used. Nephrectomized animals were fed a normal 0.1%Mg (MetS+Nx+Mg0.1%) or a supplemented 0.6%Mg (MetS+Nx+Mg0.6%) diet; Sham-operated rats with MetS receiving 0.1%Mg were used as controls. Results: As compared to controls, the MetS+Nx-Mg0.1% group showed a significant increase in oxidative stress and inflammation biomarkers (lipid peroxidation and aortic interleukin-1b and -6 expression) and Endothelin-1 levels, a decrease in nitric oxide and a worsening in uremia and MetS associated pathology as hypertension, and abnormal glucose and lipid profile. Moreover, proteomic evaluation revealed changes mainly related to lipid metabolism and CVD markers. By contrast, in the MetS+Nx+Mg0.6% group, these parameters remained largely similar to controls. Conclusion: In concurrent MetS and CKD, dietary Mg supplementation reduced inflammation and oxidative stress and improved vascular function

Assessment of Inorganic Phosphate Intake by the Measurement of the Phosphate/Urea Nitrogen Ratio in Urine

In chronic kidney disease (CKD) patients, it would be desirable to reduce the intake of inorganic phosphate (P) rather than limit the intake of P contained in proteins. Urinary excretion of P should reflect intestinal absorption of P(inorganic plus protein-derived). The aim of the present study is to determine whether the ratio of urinary P to urinary urea nitrogen (P/UUN ratio) helps identify patients with a high intake of inorganic P.A cross-sectional study was performed in 71 patients affected by metabolic syndrome with CKD (stages 2-3) with normal serum P concentration. A 3-day dietary survey was performed to estimate the average daily amount and the source of P ingested. The daily intake ofPwas1086.5 ± 361.3mg/day; 64% contained in animal proteins, 22% in vegetable proteins, and 14% as inorganic P. The total amount of P ingested did not correlate with daily phosphaturia, but it did correlate with the P/UUN ratio (p 71.1 mg/g presented more abundant inorganic P intake (p < 0.038).The P/UUN ratio is suggested to be a marker of inorganic P intake. This finding might be useful in clinical practices to identify the source of dietary P and to make personalized dietary recommendations directed to reduce inorganic P intake.This work was supported by a Spanish government grant from the Programa Nacional I+D+I 2013–2016 and Instituto de Salud Carlos III (ISCIII) Grants PI18/0138, PI17/01010 co-financing from European Funds (FEDER), Consejería de Salud and EUTOX and REDinREN from the ISCIII. J.R.M.-C. is senior researcher supported by the Nicolás Monardes Programme, Consejería de Salud-Servicio Andaluz de Salud (Junta de Andalucía).Ye