105 research outputs found
Dilemas del presente y perspectivas de futuro en el tratamiento de la osteodistrofia renal
En las últimas décadas del siglo XX, uno de los
retos más estimulantes para el nefrólogo ha sido el
control del hiperparatiroidismo secundario (HPs).
Hoy sabemos que el precio a pagar está siendo un
incremento de las calcificaciones de tejidos blandos
de las cuales las que tienen mayor repercusión clÃnica
son las calcificaciones vasculares. La «calcinosis
media» de las arterias de todos los tamaños y la
calcificación de las placas de ateroma son las responsables
de las nefastas manifestaciones clÃnicas de
isquemia de los territorios afectos. Además, el uso
generalizado de derivados de la vitamina D y compuestos
de calcio han contribuido a inclinar la balanza
del alto al bajo turnover óseo, observándose
un incremento en la prevalencia de enfermedad ósea
adinámica (EOA)1.
La importancia del control del metabolismo fosfocálcico
en los pacientes con insuficiencia renal crónica
(IRC) radica en dos hechos probados: un producto
calcio X fósforo elevado provoca mayor riesgo
de mortalidad y su corrección induce mejorÃa clÃnica.
Block y cols. en una población de 6.407 pacientes en
diálisis, encuentran que los pacientes con fósforo plasmático
superior a 6,5 mg/dl tienen mayor riesgo de
mortalidad que los que tenÃan valores inferiores. Aunque
el estudio no demuestra relación con la causa de
la muerte, los autores sugieren un posible mecanismo
cardiovascular2. Por otro lado, cuando se provoca un
balance negativo de calcio y fósforo es posible movilizar
el depósito de calcio en los tejidos extraóseos3
y la paratiroidectomÃa puede «curar» las úlceras isquémicas
provocadas por la calcifilaxis4.
El incremento en la patologÃa vascular y la mayor
prevalencia de EOA se debe también al cambio en
las caracterÃsticas de la población con un mayor porcentaje
de pacientes diabéticos y de edad avanzada.
Todo ello nos obliga a replantearnos el tratamiento
del disbalance fosfo-cálcico del paciente con IRC mirando
no sólo hacia el hueso sino también hacia los
vasos y el corazón.
Por ello, aunque quedan múltiples cuestiones por
resolver en el amplio campo de la osteodistrofia renal,
he seleccionado los dilemas clÃnicos planteados en el
presente y las perspectivas de futuro en dos áreas:
a) Enfermedad ósea de alto turnover (HPs).
b) Enfermedad ósea de bajo turnover (EOBT)
Investidura com a doctor Honoris Causa del senyor Rafael Matesanz Acedos
Recull de les intervencions i lliçons pronunciades en l’acte d'investidura com
a doctor Honoris Causa de la Universitat de Lleida del senyor Rafael Matesanz
Acedos, que es va fer a la sala VÃctor Siurana, el dia 19 de novembre de 2015
Carotid ultrasound for the early diagnosis of atherosclerosis in chronic kidney disease
Atherothrombotic disease (ATD) is a progressive
disorder and its most common clinical
manifestations, acute myocardial infarction and
stroke, are responsible for the highest morbidity and
mortality rates in the Western world. Sudden death due to
infarction with no prior symptoms occurs in 50% of men and
64% of women.1
One of the main tools to control the incidence of vascular disease
is prevention. Formulas are available to estimate cardiovascular
risk (Framingham risk score, etc.)2 They are based
on epidemiological studies that determine the risk of suffering
a cardiovascular event (fatal or non-fatal) within 5 to 10
years.3 While the available system to calculate cardiovascular
risk is easily generalisable, and universal, it does present
some difficulties. The main drawback is its low sensitivity for
detecting individuals at a high risk to suffer a cardiovascular
event. Large epidemiological studies show that 62% of subjects
with a prior history of myocardial infarction present
none or only one of the cardiovascular risk factors,4 which,
undoubtedly, prevents them from being properly identified at
a time to take effective preventive actions.
In recent years, there have been significant technological
advances in medical imaging techniques, particularly in
the field of vascular disease. Below, we describe the advantages,
disadvantages and uses of imaging techniques in
the general population and in chronic kidney disease
(CKD) patients
AsimetrÃa facial como forma de manifestación de estenosis de la vena central en hemodiálisis
Se presenta el caso de un paciente en hemodiálisis, portador de fÃstula arteriovenosa
en codo derecho como acceso para hemodiálisis, que desarrolló asimetrÃa
facial y edema de extremidad superior derecha de forma insidiosa, debido a
estenosis y posteriormente trombosis de la vena central causada por la colocación
de diversas catéteres temporales para hemodiálisis. Todo ello con escasa repercusión
sobre los parámetros de diálisis debido al desarrollo de circulación colateral.
El diagnóstico de dicha estenosis permitió la reparación y prolongación
de la vida del acceso y la resolución de la clÃnica durante dos años. Se destaca
la importancia del seguimiento del funcionamiento del acceso vascular que permita
detectar y reparar alteraciones que eviten la necesidad de recurrir a catéteres
temporales que contribuyen al fracaso de posibles futuros accesos
ADAM17 in parathyroid hyperplasia
Abstract BACKGROUND: In secondary hyperparathyroidism (SHPT), enhanced parathyroid levels of transforming growth factor-α (TGFα) increase EGF receptor (EGFR) activation causing parathyroid hyperplasia, high parathyroid hormone (PTH) and also reductions in vitamin D receptor (VDR) that limit vitamin D suppression of SHPT. Since anti-EGFR therapy is not an option in human SHPT, we evaluated ADAM17 as a therapeutic target to suppress parathyroid hyperplasia because ADAM17 is required to release mature TGFα, the most potent EGFR-activating ligand. METHODS: Computer analysis of the ADAM17 promoter identified TGFα and C/EBPβ as potential regulators of the ADAM17 gene. Their regulation of ADAM17 expression, TGFα/EGFR-driven growth and parathyroid gland (PTG) enlargement were assessed in promoter-reporter assays in A431 cells and corroborated in rat and human SHPT, using erlotinib as anti-EGFR therapy to suppress TGFα signals, active vitamin D to induce C/EBPβ or the combination. RESULTS: While TGFα induced ADAM17-promoter activity by 2.2-fold exacerbating TGFα/EGFR-driven growth, ectopic C/EBPβ expression completely prevented this vicious synergy. Accordingly, in advanced human SHPT, parathyroid ADAM17 levels correlated directly with TGFα and inversely with C/EBPβ. Furthermore, combined erlotinib + calcitriol treatment suppressed TGFα/EGFR-cell growth and PTG enlargement more potently than erlotinib in part through calcitriol induction of C/EBPβ to inhibit ADAM17-promoter activity, mRNA and protein. Importantly, in rat SHPT, the correction of vitamin D deficiency effectively reversed the resistance to paricalcitol induction of C/EBPβ to suppress ADAM17 expression and PTG enlargement, reducing PTH by 50%. CONCLUSION: In SHPT, correction of vitamin D and calcitriol deficiency induces parathyroid C/EBPβ to efficaciously attenuate the severe ADAM17/TGFα synergy, which drives PTG enlargement and high PTH.This work was supported by the following grants to A.D.: RO1 DK062713 from NIDDK; CEDAR (Center for D-receptor Activation Research); Abbott Pharmaceuticals, FIS PI11/00259 from Institutos de Salud Carlos III, Spanish Government and
the Barnes Jewish Auxilary Chapter. The processing for serum chemistries was partly supported by Core C of the O’Brien Center for renal chemistries, Grant P30DK079333
A new sex-specific formula to estimate urine protein from protein to creatinine ratio
Background: The quantification of proteinuria with the protein to creatinine ratio (PCR) is influenced by the excretion of creatinine, which, in turn, varies according to muscle mass and hence, to gender. Aims: To assess the difference between urine PCR and 24-hour urine proteinuria in men and women and to provide a formula to overcome bias caused by gender. Methods: Four hundred and forty four CKD patients were randomly divided into 2 groups: 70% were used to develop the models, while the remaining 30% were reserved to validate the formula. Epidemiological data were analyzed with chi-square and Student's t tests. Association between 24-hour proteinuria and PCR was studied with Spearman coefficient in men and women separately. Multivariate analysis was used to find variables predictive of disagreement between the 24-hour urine protein and the PCR. Equations to predict 24-hour proteinuria from PCR for men and women were plotted and validated. Results: Disagreement between 24-hour proteinuria and PCR was more pronounced in men (2.16 and 1.64 g in mean, respectively) than in women (2.00 and 2.06 g in mean, respectively). Age and gender were independent predictors of disagreement. Gender-specific equations for predicting 24-hour proteinuria were: males: 24-hour proteinuria = 1.3350*exp0.9108*ln(PCR); females: 24-hour proteinuria = 1.0068*exp0.9030*ln(PCR). Conclusions: Estimation of proteinuria with the PCR improves accuracy if gender-specific equations are used. Use of the PCR without correction for gender leads to the underestimation of proteinuria in men and overestimation in women
Efecto inhibidor directo del incremento secuencial en las dosis de calcitriol intravenoso en el hiperparatiroidismo secundario severo. Evolución a largo plazo
Estudiamos en 10 pacientes en hemodiálisis con hiperparatiroidismo secundario
severo (PTH > 50 pmol/L y calcio iónico > 4.4 mg/dl) el efecto inhibidor directo,
sobre la función paratiroidea, de incrementos secuenciales de calcitriol intravenoso
(2,4 y 6 μg post-hemodiálisis mantenidos 3,2 y 2, meses respectivamente).
En segundo lugar analizamos el indice de fracaso terapéutico (necesidad de paratiroidectomÃa)
después de 18 meses de seguimiento. Se utilizó un dializado de 2,5
mEq/l de calcio y como quelante del fósforo geles de hidróxido de aluminio para
disminuir el riesgo de hipercalcemia.
Valoramos la función paratiroidea después de los perÃodos de tratamiento con
2 y 6 μg mediante la construcción de la curva sigmoidal Ca-PTH. Consideramos
que existÃa efecto inhibidor directo, no mediado por el calcio, cuando el descenso
de los niveles de PTH intacta tras la máxima estimulación era superior al 20 % de
sus valores antes del tratamiento.
Cuatro pacientes respondieron a 2 μg. En 3 de los 6 pacientes no respondedores
el producto Ca P no permitió incrementar la dosis. De los 3 pacientes restantes
que alcanzaron la dosis de 6 μg se obtuvo respuesta en sólo 2. A los 18 meses
de seguimiento el tratamiento con calcitriol intravenoso habÃa fracasado en el 50
% de los pacientes y el resto continuaba tratamiento con dosis de mantenimiento
inferiores a las iniciales.
En conclusión, el tratamiento con calci triol intravenoso a dosis elevadas: 1)
ejerce un efecto inhibidor directo dosis-dependiente sobre los niveles de PTH; 2)
permite a largo plazo dosis de mantenimiento inferiores a las que indujeron la respuesta,
lo que sugiere un efecto «sensibilizador» sobre las células paratiroideas, y
3) fracasa en un elevado porcentaje de pacientes (50 %) con hiperparatiroidismo
secundario severo
Association of serum phosphorus with subclinical atherosclerosis in chronic kidney disease. Sex makes a difference
Abstract BACKGROUND: Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). Serum phosphate has been associated to cardiovascular disease in the general population and this effect seems to be different according to sex. In the present study we analyze the effect of phosphate on subclinical atherosclerosis in the NEFRONA population and its effect depending on sex. DESIGN: Carotid ultrasound assessing the presence of plaques was performed by an itinerant team in 1687 CKD patients not in dialysis without previous cardiovascular events. Standard blood test and anthropometrical parameters were also recorded. RESULTS: Multivariate linear regression to model phosphate levels in patients with CKD showed an interaction of sex with age. Thus, among men, serum phosphate levels declined significantly with age almost linearly. Serum phosphate levels in women under the age of 40-45 years overlapped with those in men and then stayed above, showing and overall constant relationship. Multivariate logistic regression analysis showed that higher phosphate levels associated with a higher risk of presenting atheromatous plaque. This risk however was different according to sex. In men, phosphate levels within the normal range associated with an increased risk of subclinical atheromatosis whereas in women this risk only increased with serum levels over the normal range. CONCLUSIONS: This study demonstrates that phosphate levels are associated with the presence of subclinical atheromatosis in a large CKD population. This effect of phosphate on subclinical atheromatosis was different according to sex, suggesting that a recommended serum phosphate levels could be different for male than for female CKD patients
Influencia del polimorfismo del gen receptor de la vitamina D y de la 25-hidroxivitamina D en la tensión arterial de individuos sanos
El efecto de la vitamina D sobre la tensión arterial (TA) no está bien establecido.
No existen estudios que relacionen el polimorfismo del gen del VDR con la TA.
Objetivo: Analizar la posible influencia del genotipo Bsm I y de la 25 hidroxivitamina
D3 (25OHD3) en la TA en individuos sanos y normotensos.
Métodos: Analizamos en 590 individuos sanos (260 varones y 330 mujeres)
la posible asociación de la edad, sexo, IMC, creatinina, calcio, fósforo, PTHi,
25OHD3 y genotipo Bsm I con la tensión arterial sistólica (TAS) y diastólica (TAD)
mediante un análisis de regresión lineal múltiple.
Resultados: El sexo se asoció fuertemente a la TAS (β: –12,01, p: 0,000) y a la
TAD (β: –4,78, p: 0,000), por lo que se realizó un análisis multivariante en función
del mismo. En varones, la TAS se asoció a: 25OHD3 (β: 0,36, p: 0,000), genotipo
(β: –3,90, p: 0,002) e IMC (β: 0,83, p: 0,001); y la TAD a: 25OHD3 (β:
0,16, p: 0,018) y edad (β: 0,28, p: 0,000). El análisis de la varianza mostró que
los varones con genotipo bb presentaron una TAS superior al resto de genotipos
(p: 0,007). En las mujeres, no encontramos asociación de la 25OHD3 ni del genotipo
con la TA.
Conclusiones: Los varones con mayores niveles de vitamina D presentan una
mayor TAS y TAD. Los varones con genotipo bb tienen una mayor TAS. No existe
dicha relación en el sexo femenino. Ello sugiere un posible nexo fisiopatológico
entre las hormonas sexuales y la vitamina D en el control de la tensión arterial
New perspectives on CKD-induced dyslipidemia
Abstract INTRODUCTION: Chronic kidney disease (CKD) is a world-wide health concern associated with a significantly higher cardiovascular morbidity and mortality. One of the principal cardiovascular risk factors is the lipid profile. CKD patients have a more frequent and progressive atheromatous disease that cannot be explained by the classical lipid parameters used in the daily clinical practice. Areas covered: The current review summarizes prevailing knowledge on the role of lipids in atheromathosis in CKD patients, including an overview of lipoprotein metabolism highlighting the CKD-induced alterations. Moreover, to obtain information beyond traditional lipid parameters, new state-of-the-art technologies such as lipoprotein subfraction profiling and lipidomics are also reviewed. Finally, we analyse the potential of new lipoprotein subclasses as therapeutic targets in CKD. Expert opinion: The CKD-induced lipid profile has specific features distinct from the general population. Besides quantitative alterations, renal patients have a plethora of qualitative lipid alterations that cannot be detected by routine determinations and are responsible for the excess of cardiovascular risk. New parameters, such as lipoprotein particle number and size, together with new biomarkers obtained by lipidomics will personalize the management of these patients. Therefore, nephrologists need to be aware of new insights into lipoprotein metabolism to improve cardiovascular risk assessment.This work was supported by the intramural program of the IRBLleida, Instituto de Salud Carlos III (RETIC RD16/0009/0011, FIS PI16/01354) and FEDER funds
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