Asociación de la rigidez aórtica con calcificaciones vasculares abdominales y coronarias en pacientes con enfermedad renal crónica estadios 3 y 4 / Association of aortic stiffness with abdominal vascular and coronary calcifications in patients with stage 3 and 4 chronic kidney disease

Fundamento y objetivos: El aumento de la rigidez arterial central (aórtica) tiene repercusiones hemodinámicas con efectos nocivos cardiovasculares y renales. En la enfermedad renal crónica (ERC) puede existir un aumento de la rigidez aórtica secundaria a múltiples alteraciones metabólicas, entre ellas la calcificación de la pared vascular (CV). El objetivo de este estudio fue analizar la asociación de la rigidez aórtica y de la hemodinámica central con la presencia de CV en dos territorios: aorta abdominal (CAA) y arterias coronarias (CC). Material y métodos: Se incluyeron 87 pacientes con ERC estadios 3 y 4. Usando tonometría de aplanamiento se estudiaron la hemodinámica central y la rigidez aórtica. Esta se determinó mediante la velocidad de pulso carótida-femoral (Vpc-f). A partir de la Vpc-f se calculó el índice de la VPc-f (iVpc-f) que considera otras variables que influyen en la Vpc-f, como edad, presión arterial, sexo y frecuencia cardiaca. La presencia de CAA se valoró mediante radiografía lateral de columna lumbar calculándose el índice de Kauppila (iKauppila) y las CC mediante tomografía computarizada multidetección por el método de Agatston, calculándose su índice (iAgatston). Para el estudio de la asociación entre iVpc-f, iKauppila, iAgatston, presión aórtica central, parámetros clínicos y datos de laboratorio se usaron la regresión múltiple y la regresión logística. La capacidad discriminativa del iVpc-f para evaluar la presencia de CAA y CC se determinó mediante el área bajo la curva (ABC) de ROC (receiver-operating characteristic). Resultados: La Vpc-f y el iVpc-f fueron 11,3±2,6m/s y 10,6m/s, respectivamente. El iVpc-f fue mayor cuando la ERC coexistía con diabetes mellitus (DM). Se detectaron CAA y CC en el 77% y el 87%, respectivamente. La albuminuria (β=0,13, p=0,005) y el iKauppila (β=0,36, p=0,001) se asociaron de forma independiente con la magnitud del iVpc-f... (AU)

Rationale and objectives: Increased central (aortic) arterial stiffness has hemodynamic repercussions that affect the incidence of cardiovascular and renal disease. In chronic kidney disease (CKD) there may be an increase in aortic stiffness secondary to multiple metabolic alterations including calcification of the vascular wall (VC). The objective of this study was to analyze the association of central aortic pressures and aortic stiffness with the presence of VC in abdominal aorta (AAC) and coronary arteries (CAC). Materials and methods: We included 87 patients with CKD stage 3 and 4. Using applanation tonometry, central aortic pressures and aortic stiffness were studied. We investigated the association of aortic pulse wave velocity (Pvc-f) and Pvc-f adjusted for age, blood pressure, sex and heart rate (Pvc-f index) with AAC obtained on lumbar lateral radiography and CAC assessed by multidetector computed tomography. AAC and CAC were scored according to Kauppila and Agatston methods, respectively. For the study of the association between iPvc-f index, Kauppila score, Agatston score, central aortic pressures, clinical parameters and laboratory data, multiple and logistic regression were used. We investigated the diagnosis performance of the Pvc-f index for prediction of VC using receiver-operating characteristic (ROC). Results: Pvc-f and Pvc-f index were 11.3±2.6m/s and 10.6m/s, respectively. The Pvc-f index was higher when CKD coexisted with diabetes mellitus (DM). AAC and CAC were detected in 77% and 87%, respectively. Albuminuria (β=0.13, p=0.005) and Kauppila score (β=0.36, p=0.001) were independently associated with Pvc-f index. In turn, Pvc-f index (β=0.39, p=0.001), DM (β=0.46, p=0.01), and smoking (β=0.53; p=0.006) were associated with Kauppila score, but only Pvc-f index predicted AAC [OR: 3.33 (95% CI: 1.6–6.9; p=0.001)]. The Kauppila score was independently associated with the Agatston score (β=1.53, p=0.001)... (AU)

Association of aortic stiffness with abdominal vascular and coronary calcifications in patients with stage 3 and 4 chronic kidney disease.

RATIONALE AND OBJECTIVES: Increased central (aortic) arterial stiffness has hemodynamic repercussions that affect the incidence of cardiovascular and renal disease. In chronic kidney disease (CKD) there may be an increase in aortic stiffness secondary to multiple metabolic alterations including calcification of the vascular wall (VC). The objective of this study was to analyze the association of central aortic pressures and aortic stiffness with the presence of VC in abdominal aorta (AAC) and coronary arteries(CAC). MATERIALS AND METHODS: We included 87 pacientes with CKD stage 3 and 4. Using applanation tonometry, central aortic pressures and aortic stiffness were studied. We investigated the association of aortic pulse wave velocity (Pvc-f) and Pvc-f adjusted for age, blood pressure, sex and heart rate (Pvc-f index) with AAC obtained on lumbar lateral radiography and CAC assessed by multidetector computed tomography. AAC and CAC were scored according to Kauppila and Agatston methods, respecti-vely. For the study of the association between Pvc-f index, Kauppila score, Agatston score, central aortic pressures, clinical parameters and laboratory data, multiple and logistic regression were used. We investigated the diagnosis performance of the Pvc-f index for prediction of VC using receiver-operating characteristic (ROC). RESULTS: Pvc-f and Pvc-f index were 11.3 ± 2.6 and 10.6 m/s, respectively. The Pvc-f index was higher when CKD coexisted with diabetes mellitus (DM). AAC and CAC were detected in 77% and 87%, respectively. Albuminuria (ß = 0.13, p = 0.005) and Kauppila score (ß = 0.36, p = 0.001) were independently associated with Pvc-f index. In turn, Pvc-f index (ß = 0.39, p = 0.001), DM (ß = 0.46, p = 0.01), and smoking (ß = 0.53; p = 0.006) were associated with Kauppila score, but only Pvc-f index predicted AAC [OR: 3.33 (95% CI: 1.6-6.9; p = 0.001)]. The Kauppila score was independently associated with the Agatston score (ß = 1.53, p = 0.001). The presence of AAC identified patients with CAC with a sensitivity of 73%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 38%. The Vpc-f index predicted the presence of CAC [OR: 3.35 (95% CI: 1.04-10.2, p = 0.04)]. In the ROC curves, using the Vpc-f index, the AUC for AAC and CAC was 0.82 (95%CI: 0.71-0.93, p = 0.001) and 0.81 (95% CI: 0.67-0.96, p = 0.02), respectively. CONCLUSIONS: When stage 3-4 CKD coexists with DM there is an increase in aortic stiffness determined by the Vpc-f index. In stage 3-4 CKD, AAC and CAC are very prevalent and both often coexist. The Vpc-f index is independently associated with AAC and CAC and may be useful in identifying patients with VC in these territories.

Efecto de la administración de diferentes formas de vitamina D en la presión arterial y rigidez aórticas, y su implicación en la reducción de la albuminuria en la enfermedad renal crónica / Effect of the administration of different forms of vitamin D on central blood pressure and aortic stiffness, and its implication in the reduction of albuminuria in chronic kidney disease

Antecedentes y objetivos: La vitamina D (vitD) ejerce efectos pleiotrópicos como son las modificaciones de la función arterial y descenso de la albuminuria. Existe 1-alfa-hidroxilasa tisular que convierte el 25-hidroxicolecalciferol (25[OH]D) en calcitriol que ejerce acciones autocrinas y paracrinas que intervienen en los efectos pleiotrópicos. El déficit de 25(OH)D podría limitar estos efectos tisulares de la vitD. La administración de vitD nutricional (colecalciferol) y de paricalcitol puede promover beneficios en la función vascular y renal. El objetivo fue estudiar el efecto que tiene, en la enfermedad renal crónica (ERC), la administración de diferentes formas de vitD sobre la rigidez aórtica y sobre la albuminuria, y la relación fisiopatológica entre las modificaciones de estas variables.Pacientes y métodos: Estudiamos, en 97 enfermos con ERC estadios 3-4 y con albuminuria residual, el efecto de la administración de colecalciferol (grupo 2) y paricalcitol (grupo 3) sobre la rigidez aórtica estudiada mediante la velocidad de pulso carótida-femoral (Vpc-f), sobre la presión arterial braquial y aórtica (central) y sobre la albuminuria. Un grupo de enfermos con ERC estadios 3-4 que no recibió terapia con vitD sirvió como grupo control (grupo 1). Todos los parámetros se estudiaron basalmente y tras un periodo de seguimiento de 7 ± 2 meses. Resultados: No hubo diferencias entre los grupos en la rigidez aórtica que estaba aumentada en todos ellos con un valor basal de la Vpc-f de 10,5 (9,2-12,1) m/s. Los valores basales de presión arterial sistólica braquial (PASb), presión arterial sistólica central (PASc), presión de pulso braquial (PPb) y presión de pulso central (PPc) fueron similares en todos los grupos. El valor de albuminuria basal fue 198 (46-832) mg/g, sin diferencias entre los grupos.(AU)

Background and objectives: Vitamin D(vitD) participates in phospho-calcium metabolism and exerts multiple pleiotropic effects. There is tissue 1-α (OH)ase that converts 25-OH cholecalciferol (25 (OH) D) in calcitriol that exerts autocrine and paracrine effects. 25 (OH)D deficiency could limit these tissue effects of vitD. The administration of nutritional vitD and the activator of the vitD receptor, paricalcitol, may promote beneficial effects on vascular and renal function. The objective of this work was to study in subjects with chronic kidney disease (CKD) the effect that the administration of different forms of vitD has on arterial function and albuminuria, and the possible relationship between the modifications of these variables. Patients and methods: We studied in 97 patients with CKD stages 3-4 the effect of the administration of cholecalciferol (group 2; n: 35) and paricalcitol (n: 31; group 3) on parameters derived from brachial blood pressure, aortic blood pressure and on aortic stiffness studied using carotid-femoral pulse velocity (Vpc-f), and on albuminuria. A group of patients with stages 3-4 CKD who did not receive vitD therapy served as a control group (n: 31; group 1). All parameters were studied at baseline and after the follow-up period which was 7 ± 2 months. Results: In the baseline phase, no differences were observed between the groups in brachial systolic blood pressure (bSBP), central systolic blood pressure (SBP), brachial pulse pressure (bPP), and central pulse pressure (pCP) or in aortic stiffness that was increased in all groups with a baseline Vpc-f value of 10.5 (9.2-12.1) m/sec. The baseline albuminuria value in the grouped patients was 229 (43-876) mg / g (median (interquartile range)), with no differences between the groups.(AU)

Effect of the administration of different forms of vitamin D on central blood pressure and aortic stiffness, and its implication in the reduction of albuminuria in chronic kidney disease. / Efecto de la administración de diferentes formas de vitamina D en la presión arterial y rigidez aórticas, y su implicación en la reducción de la albuminuria en la enfermedad renal crónica.

BACKGROUND AND OBJECTIVES: Vitamin D(vitD) participates in phospho-calcium metabolism and exerts multiple pleiotropic effects. There is tissue 1-α (OH)ase that converts 25-OH cholecalciferol (25 (OH) D) in calcitriol that exerts autocrine and paracrine effects. 25 (OH)D deficiency could limit these tissue effects of vitD. The administration of nutritional vitD and the activator of the vitD receptor, paricalcitol, may promote beneficial effects on vascular and renal function. The objective of this work was to study in subjects with chronic kidney disease (CKD) the effect that the administration of different forms of vitD has on arterial function and albuminuria, and the possible relationship between the modifications of these variables. PATIENTS AND METHODS: We studied in 97 patients with CKD stages 3-4 the effect of the administration of cholecalciferol (group 2; n: 35) and paricalcitol (n: 31; group 3) on parameters derived from brachial blood pressure, aortic blood pressure and on aortic stiffness studied using carotid-femoral pulse velocity (Vpc-f), and on albuminuria. A group of patients with stages 3-4 CKD who did not receive vitD therapy served as a control group (n: 31; group 1). All parameters were studied at baseline and after the follow-up period which was 7 ± 2 months. RESULTS: In the baseline phase, no differences were observed between the groups in brachial systolic blood pressure (bSBP), central systolic blood pressure (SBP), brachial pulse pressure (bPP), and central pulse pressure (pCP) or in aortic stiffness that was increased in all groups with a baseline Vpc-f value of 10.5 (9.2-12.1) m/sec. The baseline albuminuria value in the grouped patients was 229 (43-876) mg / g (median (interquartile range)), with no differences between the groups. Serum calcium and phosphorus increased significantly in those treated with cholecal-ciferol (native vitD) and paricalcitol (active vitD). Parathormone (PTH) values decreased in those treated with paricalcitol.bPP and cPP decreased in all groups treated with native and active vitD. No significant changes in bPP and cPP were observed in the control group. Vpc-f did not change significantly in any of the groups, although the variation was quantitatively greater in group 3 (11.2±2 vs. 10.7±1.6 (P=.06)). No differences were observed in the changes in Vpc-f between the groups when adjusted to the baseline values of estimated glomerular filtration rate (eGFR), albuminuria, PTH, vitD, brachial and central blood pressure parameters, and their changes with treatment.Those who received treatment with native and active vitD presented a significant decrease in albuminuria of 17% (group 2) and 21% (group 3) compared to a 16% increase in the untreated group (group 1) (P=.01). A decrease in albuminuria ≥30% was observed more frequently in the groups treated with some form of vitD (group 2: 23%; group 3: 45%) than in the control group (13%) (P=.03). The decrease in albuminuria observed in the groups treated with any of the forms of vitD did not vary when the baseline values of the biochemical parameters of phosphorus-calcium metabolism, those of arterial function (PPb, PPc, Vpc-f) or its modifications were introduced as covariates. There was no significant correlation between changes in Vpc-f and albuminuria. In logistic regression, changes in arterial function parameters were also not explanatory for the ≥30% decrease in albuminuria. CONCLUSIONS: In patients with CKD stages 3-4, treated with RAS blockers and with residual albuminuria, the administration of or paricalcitol reduces brachial and aortic pulse pressures, and albuminuria. The decrease in albuminuria does not seem to be mediated, at least not decisively, by changes in central hemodynamics or aortic stiffness.

Papel del aumento de la rigidez arterial central en el daño macro y microvascular en pacientes con enfermedad coronaria / Role of increased central arterial stiffness in macro and microvascular damage in patients with coronary artery disease

Antecedentes: Con frecuencia, los pacientes con cardiopatía tienen disfunción renal manifestada por el descenso del filtrado glomerular (FG) y/o aumento de la albuminuria. Objetivos: El objetivo fue estudiar el papel del aumento de la rigidez aórtica en la presencia y extensión de la enfermedad coronaria (EC) y en la disfunción renal en sujetos con EC. Pacientes y métodos: Estudio observacional transversal de 48 pacientes con sospecha de EC sometidos a coronariografía. Mediante tonometría de aplanamiento sobre la arterial radial y aplicando una función de transferencia, se calcularon los valores de presión arterial central. El estudio de la rigidez aórtica se hizo mediante la determinación de la velocidad de pulso carótida-femoral (Vpc-f). Resultados: De los 48 pacientes, 11 no tenían lesiones coronarias significativas, 24 evidenciaron lesiones significativas en una o dos arterias coronarias y 13 en ≥ tres arterias. El grupo con mayor grado de EC tenía valores de presión de pulso central (PPc) más altos que el grupo sin EC. La Vpc-f aumentaba de forma progresiva y significativa con el grado de EC. La regresión logística mostraba que la VPc-f predecía de forma independiente la presencia de EC. El FG se correlacionaba de forma negativa y significativa con la edad. La Vpc-f se asociaba a la albuminuria. Conclusiones: En pacientes con EC estable, la Vpc-f se relaciona de forma independiente con la existencia y extensión de la EC, así como con la disminución del FG y el aumento de la albuminuria.(AU)

Background: Patients with heart disease frequently have renal dysfunction manifested by a decrease in glomerular filtration rate (GFR) and / or increase of albuminuria. Objectives: The objective was to study the possible role of increased aortic stiffness in the presence and extent of coronary artery disease (CAD) and kidney dysfunction in a group of patients with suspected CAD. Patients and methods: We studied forty-eight patients undergoing coronariography for suspected coronary disease (CAD). Using applanation tonometry on the radial artery and applying a transfer function, central blood pressure values were calculated. The study of aortic stiffness was done by determining the carotid-femoral pulse velocity (Pvc-f). Results: Of the 48 patients, 11 had no significant coronary lesions, 24 showed significant lesions in 1 or 2 coronary arteries and 13 in ≥ 3 arteries. The group with a higher degree of CD had significantly higher cPP values than the group without CD. The Pvc-f increased progressively and significantly with the degree of CD. The logistic regression showed that Pvc-f independently predicted the presence of CD. The relative risk of CD increased 2.5 times for each meter of increase in Pvc-f. The GFR was negatively and significantly correlated with age and Pvc-f was associated with albuminuria. Conclusions: In patients with stable CD, Pvc-f, expression of aortic stiffness, is independently associated with the existence of CD and its degree of extension. The increase in arterial stiffness also participates in the decrease in GFR and in the increase in albuminuria.(AU)

Role of increased central arterial stiffness in macro and microvascular damage in patients with coronary artery disease. / Papel del aumento de la rigidez arterial central en el daño macro y microvascular en pacientes con enfermedad coronaria.

BACKGROUND: Patients with heart disease frequently have renal dysfunction manifested by a decrease in glomerular filtration rate (GFR) and / or increase of albuminuria. OBJECTIVES: The objective was to study the possible role of increased aortic stiffness in the presence and extent of coronary artery disease (CAD) and kidney dysfunction in a group of patients with suspected CAD. PATIENTS AND METHODS: We studied forty-eight patients undergoing coronariography for suspected coronary disease (CAD). Using applanation tonometry on the radial artery and applying a transfer function, central blood pressure values were calculated. The study of aortic stiffness was done by determining the carotid-femoral pulse velocity (Pvc-f). RESULTS: Of the 48 patients, 11 had no significant coronary lesions, 24 showed significant lesions in 1 or 2 coronary arteries and 13 in ≥ 3 arteries. The group with a higher degree of CD had significantly higher cPP values than the group without CD. The Pvc-f increased progressively and significantly with the degree of CD. The logistic regression showed that Pvc-f independently predicted the presence of CD. The relative risk of CD increased 2.5 times for each meter of increase in Pvc-f. The GFR was negatively and significantly correlated with age and Pvc-f was associated with albuminuria. CONCLUSIONS: In patients with stable CD, Pvc-f, expression of aortic stiffness, is independently associated with the existence of CD and its degree of extension. The increase in arterial stiffness also participates in the decrease in GFR and in the increase in albuminuria.

Anticoagulación oral en la enfermedad renal crónica con fibrilación auricular / Oral anticoagulation in chronic kidney disease with atrial fibrillation

La enfermedad renal crónica (ERC) y la fibrilación auricular (FA) frecuentemente coexisten, amplificando el riesgo de eventos cardiovasculares y de mortalidad. En pacientes con ERC estadio 3 y FA no valvular los anticoagulantes orales de acción directa (ACOD) han demostrado, comparados con antagonistas de la vitamina K (AVK), igual o superior eficacia en la prevención de ictus y embolismo sistémico, y mayor seguridad. No existen ensayos aleatorizados de la eficacia y la seguridad de ACOD y AVK en la ERC avanzada. Por otra parte, estudios observacionales sugieren que los ACOD, comparados con warfarina, se asocian a menor riesgo de daño renal agudo y de generación/progresión de la ERC. En este trabajo se revisan los aspectos epidemiológicos y fisiopatológicos de la asociación ERC y FA, las evidencias de la eficacia y seguridad de la warfarina y de los ACOD en las diversas fases de la ERC con FA, así como la comparación entre warfarina y ACOD en la eficacia y seguridad anticoagulante, y en sus efectos renales

Chronic kidney disease (CKD) and atrial fibrillation (AF) frequently coexist, amplifying the risk of cardiovascular events and mortality. In patients with CKD stage 3 and non-valvular AF, direct oral anticoagulants (DOACs) have shown, compared to vitamin K antagonists (VKA), equal or greater efficacy in the prevention of stroke and systemic embolism, and greater safety. There are no randomized trials of the efficacy and safety of DOACs and VKA in advanced CKD. On the other hand, observational studies suggest that DOACs, compared to warfarin, are associated with a lower risk of acute kidney damage and generation/progression of CKD. This paper reviews the epidemiological and pathophysiological aspects of the CKD and AF association, the evidence of the efficacy and safety of warfarin and ACODs in various stages of CKD with AF as well as the comparison between warfarin and ACODs in efficacy and anticoagulant safety, and in its renal effects

Oral anticoagulation in chronic kidney disease with atrial fibrillation.

Chronic kidney disease (CKD) and atrial fibrillation (AF) frequently coexist, amplifying the risk of cardiovascular events and mortality. In patients with CKD stage 3 and non-valvular AF, direct oral anticoagulants (DOACs) have shown, compared to vitamin K antagonists (VKA), equal or greater efficacy in the prevention of stroke and systemic embolism, and greater safety. There are no randomizedtrials of the efficacy and safety of DOACs and VKA in advanced CKD. On the other hand, observational studies suggest that DOACs, compared to warfarin, are associated with a lower risk of acute kidney damage and generation/progression of CKD. This paper reviews the epidemiological and pathophysiological aspects of the CKD and AF association, the evidence of the efficacy and safety of warfarin and ACODs in various stages of CKD with AF as well as the comparison between warfarin and ACODs in efficacy and anticoagulant safety, and in its renal effects.

Mineralcorticoid receptor blockers in chronic kidney disease.

There are many experimental data supporting the involvement of aldosterone and mineralcorticoid receptor (MR) activation in the genesis and progression of chronic kidney disease (CKD) and cardiovascular damage. Many studies have shown that in diabetic and non-diabetic CKD, blocking the renin-angiotensin-aldosterone (RAAS) system with conversion enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) decreases proteinuria, progression of CKD and mortality, but there is still a significant residual risk of developing these events. In subjects treated with ACEi or ARBs there may be an aldosterone breakthrough whose prevalence in subjects with CKD can reach 50%. Several studies have shown that in CKD, the aldosterone antagonists (spironolactone, eplerenone) added to ACEi or ARBs, reduce proteinuria, but increase the risk of hyperkalemia. Other studies in subjects treated with dialysis suggest a possible beneficial effect of antialdosteronic drugs on CV events and mortality. Newer potassium binders drugs can prevent/decrease hyperkalemia induced by RAAS blockade, and may reduce the high discontinuation rates or dose reduction of RAAS-blockers. The nonsteroidal MR blockers, with more potency and selectivity than the classic ones, reduce proteinuria and have a lower risk of hyperkalemia. Several clinical trials, currently underway, will determine the effect of classic MR blockers on CV events and mortality in subjects with stage 3b CKD and in dialysis patients, and whether in patients with type 2 diabetes mellitus and CKD, optimally treated and with high risk of CV and kidney events, the addition of finerenone to their treatment produces cardiorenal benefits. Large randomized trials have shown that sodium glucose type 2 cotransporter inhibitors (SGLT2i) reduce mortality and the development and progression of diabetic and nondiabetic CKD. There are pathophysiological arguments, which raise the possibility that the triple combination ACEi or ARBs, SGLT2i and aldosterone antagonist provide additional renal and cardiovascular protection.

Oral anticoagulation in chronic kidney disease with atrial fibrillation. / Anticoagulación oral en la enfermedad renal crónica con fibrilación auricular.

Chronic kidney disease (CKD) and atrial fibrillation (AF) frequently coexist, amplifying the risk of cardiovascular events and mortality. In patients with CKD stage3 and non-valvular AF, direct oral anticoagulants (DOACs) have shown, compared to vitaminK antagonists (VKA), equal or greater efficacy in the prevention of stroke and systemic embolism, and greater safety. There are no randomized trials of the efficacy and safety of DOACs and VKA in advanced CKD. On the other hand, observational studies suggest that DOACs, compared to warfarin, are associated with a lower risk of acute kidney damage and generation/progression of CKD. This paper reviews the epidemiological and pathophysiological aspects of the CKD and AF association, the evidence of the efficacy and safety of warfarin and ACODs in various stages of CKD with AF as well as the comparison between warfarin and ACODs in efficacy and anticoagulant safety, and in its renal effects.

[Mineralcorticoid receptor blockers in chronic kidney disease]. / Bloqueantes del receptor mineralcorticoide en la enfermedad renal crónica.

There are many experimental data supporting the involvement of aldosterone and mineralcorticoid receptor (MR) activation in the genesis and progression of chronic kidney disease (CKD) and cardiovascular damage. Many studies have shown that in diabetic and non-diabetic CKD, blocking the renin- angiotensin-aldosterone (RAAS) system with conversion enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) decreases proteinuria, progression of CKD and mortality, but there is still a significant residual risk of developing these events. In subjects treated with ACEi or ARBs there may be an aldosterone breakthrough whose prevalence in subjects with CKD can reach 50%. Several studies have shown that in CKD, the aldosterone antagonists (spironolactone, eplerenone) added to ACEi or ARBs, reduce proteinuria, but increase the risk of hyperkalemia. Other studies in subjects treated with dialysis suggest a possible beneficial effect of antialdosteronic drugs on CV events and mortality. Newer potassium binders drugs can prevent / decrease hyperkalemia induced by RAAS blockade, and may reduce the high discontinuation rates or dose reduction of RAAS-blockers. The nonsteroidal MR blockers, with more potency and selectivity than the classic ones, reduce proteinuria and have a lower risk of hyperkalemia. Several clinical trials, currently underway, will determine the effect of classic MR blockers on CV events and mortality in subjects with stage 3b CKD and in dialysis patients, and whether in patients with type 2 diabetes mellitus and CKD, optimally treated and with high risk of CV and kidney events, the addition of finerenone to their treatment produces cardiorenal benefits. Large randomized trials have shown that sodium glucose type 2 cotransporter inhibitors (SGLT2i) reduce mortality and the development and progression of diabetic and nondiabetic CKD. There are pathophysiological arguments, which raise the possibility that the triple combination ACEi or ARBs, SGLT2i and aldosterone antagonist provide additional renal and cardiovascular protection.

Efecto de dapagliflozina sobre la rigidez arterial en pacientes con diabetes mellitus tipo 2 / Effect of dapagliflozin on arterial stiffness in patients with type 2 diabetes mellitus

Introducción y objetivos: Los antidiabéticos orales inhibidores del cotransportador sodio-glucosa (iSGLT2) reducen la morbimortalidad cardiovascular en la DM2. El aumento de la rigidez arterial puede participar en esta morbimortalidad. El objetivo de este trabajo fue analizar el efecto de la administración de dapagliflozina en la rigidez arterial. Pacientes y métodos: Estudio observacional, prospectivo que incluyó a 32 pacientes con DM2. Antes del inicio de dapagliflozina y a los 6 y 12 meses, se analizaron parámetros bioquímicos en sangre y orina. Basalmente y a los 12 meses se determinó la velocidad de pulso carótida-femoral (VPc-f) mediante tonometría. El análisis de los cambios en las variables y su interrelación se hizo mediante ANOVA de datos repetidos, test de Wilcoxon y regresión múltiple. Resultados: Se objetivó un descenso significativo de la VPc-f. No se evidenció asociación entre descenso de VPc-f y cambios de la glucemia, la uricemia, la presión arterial ni del peso. Conclusiones: Dapagliflozina, en sujetos con DM2, produce, a medio-largo plazo, una disminución de la rigidez arterial

Introduction: Oral antidiabetic inhibitors of the sodium-glucose cotransporter (SGLT2i) reduce cardiovascular morbidity and mortality in DM2. The increase in arterial stiffness can participate in this morbidity and mortality. The aim of this study was to analyse the effect of the administration of dapagliflozin on arterial stiffness. Patients and methods: Prospective observational study that included 32 patients with DM2. Before starting dapagliflozin, and at 6 and 12 months, biochemical parameters in blood and urine were analysed. Before starting dapagliflozin and at 12 months the velocity of the carotid-femoral pulse (VPc-f) was determined by tonometry. Changes in the variables and their interrelation was analysed by repeated data ANOVA, Wilcoxon's test and multiple regression. Results: A significant decrease in the VPc-f was observed. There was no association between decreased VPc-f and changes in blood glucose, uric acid, blood pressure or weight. Conclusions: Dapagliflozin, in subjects with DM2, produces a medium to long-term decrease in arterial stiffness

Effect of dapagliflozin on arterial stiffness in patients with type 2 diabetes mellitus. / Efecto de dapagliflozina sobre la rigidez arterial en pacientes con diabetes mellitus tipo 2.

INTRODUCTION: Oral antidiabetic inhibitors of the sodium-glucose cotransporter (SGLT2i) reduce cardiovascular morbidity and mortality in DM2. The increase in arterial stiffness can participate in this morbidity and mortality. The aim of this study was to analyse the effect of the administration of dapagliflozin on arterial stiffness. PATIENTS AND METHODS: Prospective observational study that included 32 patients with DM2. Before starting dapagliflozin, and at 6 and 12 months, biochemical parameters in blood and urine were analysed. Before starting dapagliflozin and at 12 months the velocity of the carotid-femoral pulse (VPc-f) was determined by tonometry. Changes in the variables and their interrelation was analysed by repeated data ANOVA, Wilcoxon's test and multiple regression. RESULTS: A significant decrease in the VPc-f was observed. There was no association between decreased VPc-f and changes in blood glucose, uric acid, blood pressure or weight. CONCLUSIONS: Dapagliflozin, in subjects with DM2, produces a medium to long-term decrease in arterial stiffness.

Perfil de seguridad renal de los inhibidores del cotransportador sodio-glucosa tipo 2 y otros datos de seguridad / Renal safety profile of sodium-glucose cotransporter-2 inhibitors and other safety data

Los inhibidores del SGLT2 tienen como efecto principal una acción glucosúrica y logran revertir el efecto deletéreo del aumento de la reabsorción tubular de glucosa en las personas con diabetes mellitus tipo 2 (DM2). En términos de eficacia producen una reducción de HbA1c promedio del 0,8%, aunque si se parte de una HbA1c más elevada se pueden tener reducciones mayores. Además de los efectos glucémicos, como efectos complementarios se obtiene la reducción de peso y de presión arterial sin aumentar las hipoglucemias. Por su mecanismo de acción independiente de la insulina se pueden utilizar en monoterapia, en pacientes intolerantes a la metformina o en combinación con otros medicamentos hipoglucemiantes, incluyendo la insulina. Los efectos secundarios son pocos y los más frecuentes están relacionados con su mecanismo de acción. Destacan las infecciones genitourinarias, las más frecuentes son las micóticas. Por otro lado, su perfil cardiovascular (CV) es adecuado y queda por aclarar la aparición de cetoacidosis (CAD), en posible relación a su uso en pacientes insulinopénicos. En un ensayo clínico aleatorizado de un iSGLT2 en pacientes con diabetes mellitus tipo 2 y enfermedad CV de base, se ha podido observar que el uso de este en asociación a la terapia estándar logra enlentecer la progresión del daño renal y disminuir eventos renales relevantes, como la duplicación de los valores de creatinina sérica y el inicio de diálisis. Estos efectos, probablemente se fundamentan en sus efectos favorables sobre la hemodinámica glomerular disminuyendo la hiperfiltración, en la reducción de la toxicidad tubular de la glucosa, así como sus efectos beneficiosos sobre la glucemia, la presión arterial, el peso y la uricemia (AU)

The main effect of SGLT2 inhibitors is their glycosuric action. These drugs reverse the deleterious effect of increased glucose reabsorption by the renal tubule in persons with DM2. In terms of efficacy, SGLT2 inhibitors produce a mean HbA1c reduction of 0.8%, although higher initial HbA1c levels can show a larger decrease. In addition to these glycaemic effects, this drug class also favours weight loss and blood pressure control, without increasing hypoglycaemic episodes. Due to their insulin-independent mechanism of action, SGLT2 inhibitors can be used in monotherapy, in patients with metformin intolerance, or in combination with other glucose-lowering drugs, including insulin. These drugs have few secondary effects and most are related to their mechanism of action. The most frequent adverse effects are genitourinary infections, usually mycotic infections. SGLT2 inhibitors have an adequate cardiovascular safety profile. The development of ketoacidosis remains to be elucidated, and may be related to use in patients with insulinopenia. A randomised clinical trial of an SGLT2 inhibitor in patients with DM2 and underlying cardiovascular disease showed that its use in association with standard therapy slowed the progression of renal damage and reduced significant renal events such as doubling of serum creatinine values and initiation of dialysis. These effects are probably due to the favourable effects of SGLT2 inhibition on glomerular haemodynamics, by reducing hyperfiltration, to the reduction of glucose-induced tubular toxicity, as well as its beneficial effects on glycaemia, blood pressure, weight, and uricaemia (AU)

Renal safety profile of sodium-glucose cotransporter-2 inhibitors and other safety data. / Perfil de seguridad renal de los inhibidores del cotransportador sodio-glucosa tipo 2 y otros datos de seguridad.

The main effect of SGLT2 inhibitors is their glycosuric action. These drugs reverse the deleterious effect of increased glucose reabsorption by the renal tubule in persons with DM2. In terms of efficacy, SGLT2 inhibitors produce a mean HbA1c reduction of 0.8%, although higher initial HbA1c levels can show a larger decrease. In addition to these glycaemic effects, this drug class also favours weight loss and blood pressure control, without increasing hypoglycaemic episodes. Due to their insulin-independent mechanism of action, SGLT2 inhibitors can be used in monotherapy, in patients with metformin intolerance, or in combination with other glucose-lowering drugs, including insulin. These drugs have few secondary effects and most are related to their mechanism of action. The most frequent adverse effects are genitourinary infections, usually mycotic infections. SGLT2 inhibitors have an adequate cardiovascular safety profile. The development of ketoacidosis remains to be elucidated, and may be related to use in patients with insulinopenia. A randomised clinical trial of an SGLT2 inhibitor in patients with DM2 and underlying cardiovascular disease showed that its use in association with standard therapy slowed the progression of renal damage and reduced significant renal events such as doubling of serum creatinine values and initiation of dialysis. These effects are probably due to the favourable effects of SGLT2 inhibition on glomerular haemodynamics, by reducing hyperfiltration, to the reduction of glucose-induced tubular toxicity, as well as its beneficial effects on glycaemia, blood pressure, weight, and uricaemia.

Medida de la presión arterial en consulta y automatizada (BPTru®) para evaluar el efecto de bata blanca / Measurement of blood pressure in consultation and automated mesurement (BPTru ®) to evaluate the white coat effect

Fundamento y objetivo: El efecto de bata blanca (EBB) es uno de los principales sesgos que pueden modificar la medida de la presión arterial (PA) en consulta, por lo que se debe considerar para evitar errores diagnóstico-terapéuticos en los pacientes hipertensos. La utilización de aparatos automatizados en consulta podría disminuir dicho efecto. Método: Se diseñaron 2 estudios con el objetivo de evaluar las diferencias entre la medida rutinaria en consulta y la obtenida por el aparato automatizado de medida de PA en consulta, BPTru®, así como su influencia en el EBB. El primero de los estudios, TRUE-ESP, incluyó pacientes normotensos e hipertensos atendidos en consultas especializadas de Cardiología, Nefrología, Medicina Interna, Endocrinología y Medicina Familiar. El segundo, TRUE-HTA, incluyó pacientes hipertensos atendidos en una Unidad de HTA, protocolizada, con personal entrenado. Resultados: El estudio TRUE-ESP incluyó 300 pacientes, 76% hipertensos. Se observó una diferencia significativa entre la medida clínica y la medida BPTru® (media [DE] de PA sistólica/PA diastólica [PAS/PAD] de 9,8 [6,11]/3,4 [7,9] mmHg, p<0,001). El porcentaje de pacientes que cumplió criterios de EBB fue del 27,7%. El estudio TRUE-HTA incluyó 101 pacientes hipertensos. Se observó una diferencia significativa entre la medida clínica y la medida mediante BPTru® (media [DE] de PAS/PAD de 5,7 [3,9]/2,1 [3,5] mmHg, p<0,001) y la medida del período de actividad de la monitorización ambulatoria de la PA (MAPA) (media [DE] de PAS/PAD de 8,5 [6,7]/3,5 [2,5] mmHg, p<0,001). El porcentaje de pacientes que cumplió criterios de EBB fue del 32,1%. Conclusiones: El empleo de aparatos automatizados de medida de PA en consulta, como el BPTru®, puede colaborar a disminuir el EBB y mejorar la precisión de la medida de la PA en consulta (AU)

Background and objective: White coat effect (WCE) is one of the main bias that can affect office blood pressure (BP) measurement. Therefore, it is a factor must be considered in hypertensives to avoid mistakes in diagnosis and/or treatment. Employment of automated office BP (AOBP) devices could diminish that effect. Methods: Two studies were designed with the objective of evaluating differences between routinely office and AOBP measurements. WCE was also assessed. First, the TRUE-ESP study included normotensive and hypertensive patients attending specialized consultations at Cardiology, Nephrology, Internal Medicine, Endocrinology and Family Practice. Second, the TRUE-HTA study included hypertensives attending a protocoled Hypertension Unit, with a trained staff. Results: TRUE-ESP study included 300 patients, 76% being hypertensives. A significant difference between office BP and AOBP measurement (SBP/DBP 9.8±11.6/3.4±7.9mmHg, P<.001) was observed. Percentage of patients gathering WCE criteria was 27.7%. TRUE-HTA study included 101 hypertensive patients. A significant difference between office BP and AOBP measurement (SBP/DBP 5.7±9.3/2.1±5.3mmHg, P<.001) and activity period-ABPM (SBP/DBP 8.5±6.7/3.5±2.5mmHg, P<.001) was observed. Percentage of WCE patients was 32.1%. Conclusions: Use of AOBP devices can contribute to decrease WCE and to improve accuracy of office BP measurement (AU)

[Measurement of blood pressure in consultation and automated mesurement (BPTru(®)) to evaluate the white coat effect]. / Medida de la presión arterial en consulta y automatizada (BPTru®) para evaluar el efecto de bata blanca.

BACKGROUND AND OBJECTIVE: White coat effect (WCE) is one of the main bias that can affect office blood pressure (BP) measurement. Therefore, it is a factor must be considered in hypertensives to avoid mistakes in diagnosis and/or treatment. Employment of automated office BP (AOBP) devices could diminish that effect. METHODS: Two studies were designed with the objective of evaluating differences between routinely office and AOBP measurements. WCE was also assessed. First, the TRUE-ESP study included normotensive and hypertensive patients attending specialized consultations at Cardiology, Nephrology, Internal Medicine, Endocrinology and Family Practice. Second, the TRUE-HTA study included hypertensives attending a protocoled Hypertension Unit, with a trained staff. RESULTS: TRUE-ESP study included 300 patients, 76% being hypertensives. A significant difference between office BP and AOBP measurement (SBP/DBP 9.8±11.6/3.4±7.9 mmHg, P<.001) was observed. Percentage of patients gathering WCE criteria was 27.7%. TRUE-HTA study included 101 hypertensive patients. A significant difference between office BP and AOBP measurement (SBP/DBP 5.7±9.3/2.1±5.3 mmHg, P<.001) and activity period-ABPM (SBP/DBP 8.5±6.7/3.5±2.5 mmHg, P<.001) was observed. Percentage of WCE patients was 32.1%. CONCLUSIONS: Use of AOBP devices can contribute to decrease WCE and to improve accuracy of office BP measurement.

La pro-renina y su receptor. Papel de la inhibición directa de la renina / Prorenin and its receptor: the role of direct renin inhibition

El reciente descubrimiento de un receptor de (pro-)renina, al que se unen pro-renina y renina, ha renovado el interés por la pro-renina. Esta es el precursor de la renina sintetizada en el aparato yuxtaglomerular y se produce también extrarrenalmente. En situaciones clínicas como la diabetes, hay valores elevados de prorenina en plasma que se asocian a daño microvascular. Tras unirse al receptor, la pro-renina experimenta una activación no proteolítica que consiste en la separación del prosegmento, lo que le confiere capacidad catalítica para generar angiotensina I a partir del angiotensinógeno. Por otra parte, la unión de (pro-)renina al receptor induce la activación de cinasas que intervienen en la diferenciación celular (neuronal) y en la formación de citocinas fibrogénicas y otros mediadores de lesión tisular. Además de ejercer efectos relacionados con el sistema renina-angiotensina-aldosterona (SRAA), el receptor (pro-)renina se une a la ATPasa vacuolada, implicada en la acidificación intracelular y en otras importantes funciones para la viabilidad celular. El uso de un péptido similar a una parte del prosegmento de la pro-renina que impide la unión de pro-renina al receptor ha dado resultados discrepantes en modelos experimentales. En algunos casos, ha sido eficaz para prevenir o atenuar la nefropatía diabética y la fibrosis cardiaca y en otros no. Los inhibidores directos de la renina (IDR) tienen capacidad de unirse a la (pro-)renina ligada al receptor e impedir su acción catalítica. La mayoría de los estudios no evidencian la capacidad de los IDR para suprimir los efectos no catalíticos (no dependientes de la angiotensina II) del complejo (pro-)renina-receptor. Todavía hay muchos interrogantes sobre el papel de la pro-renina en la generación tisular e intracelular de la angiotensina II, los efectos intracelulares inducidos por la unión pro-renina-receptor y sobre la relevancia de la función del receptor (pro-)renina no relacionado con el SRA. Asimismo, surgen muchas cuestiones sobre posibles agentes que bloqueen el receptor (pro-)renina y sobre el efecto de los IDR en las consecuencias celulares, dependientes e independientes de la angiotensina II, de la interacción (pro-)renina-receptor (AU)

The recent discovery of a (pro)renin receptor that binds both prorenin and renin has renewed interest in prorenin. Prorenin is the precursor of renin and is synthesized mainly in the juxtaglomerular apparatus, although it is also produced outside the kidney. In clinical conditions such as diabetes mellitus, high plasma levels of prorenin are observed to occur in association with microvascular damage. After binding to its receptor, prorenin undergoes nonproteolytic activation, which involves separation of the prosegment. Through this process the molecule acquires the ability to catalyze the production of angiotensin I from angiotensinogen. On the other hand, the binding of (pro)renin to its receptor induces the activation of a number of kinases involved in the differentiation of neuronal cells and in the production of fibrogenic cytokines and other mediators of tissue damage. As well as having an effect on the renin-angiotensinaldosterone system (RAAS), the (pro)renin receptor binds to vacuolar ATPase, which is involved in intracellular acidification and other processes vital for cell viability. Experimental studies with a synthetic peptide which is similar to part of the prorenin prosegment and which prevents prorenin binding with its receptor have produced conflicting findings. In some cases, the peptide has been effective in preventing or reducing diabetic nephropathy and cardiac fibrosis, while in others it has not. Direct renin inhibitors (DRIs) are able to bind to receptor-bound (pro)renin, thereby blocking its catalytic activity. Most studies have found no evidence that DRIs are able to suppress the noncatalytic (i.e. non-angiotensin-II-dependent) effects of the (pro)renin-receptor complex. There are still many unanswered questions about the role of prorenin in the production of both tissular and intracellular angiotensin II, about the intracellular effects induced by the binding of prorenin to its receptor, and about the importance of the (pro)renin receptor beyond its effect on the RAAS. Similarly, many questions have arisen about drugs that can block the (pro)renin receptor and about the effect of DRIs on the cellular implications of the interaction between (pro)renin and its receptor, whether dependent on or independent of angiotensin II (AU)

Comparison of the MDRD and the CKD-EPI equations to estimate the glomerular filtration rate in the general population

Background and objective: The Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI) equation has been proposed as a replacement for the Modification of Diet in Renal Disease (MDRD) equation to estimate the glomerular filtration rate, but this equation has not yet been evaluated in the general population. Patients and methods: Cross-sectional analysis of a random sample of 858 participants from the general population aged 50–75 years without known kidney disease. The prevalence of low eGFR (<60mL/min/1.73m2) was assessed with the MDRD and the CKD-EPI equations in the overall sample and in normoalbuminuric individuals. Results: With the MDRD equation the median eGFRs (interquartile range) in men/women were 63.3(12.2)/56.7(9.4) mL/min/1.73m2, and with the CKD-EPI equation 66.6(14.2)/61.3(11.6) mL/min/1.73m2. The prevalence of low eGFR in men/women was 35.2%/68.5% and 25.1%/45.7% with the MDRD and the CKD-EPI equations, respectively. Normoalbuminuric women without risk factors for CKD experience the most pronounced reduction in the number of cases with low eGFR with the CKD-EPI equation. The prevalence of renal impairment in this subgroup still remained even greater than that in men with diabetes, hypertension, or cardiovascular disease. Conclusions: Compared with the MDRD, the CKD-EPI equation generates a substantial reduction in the prevalence of renal impairment in subjects with diabetes, hypertension, cardiovascular disease, and in subjects without risk factors. The prevalence of renal impairment in normoalbuminuric females may be still overestimated with the CKD-EPI equation (AU)

Fundamento y objetivo: La ecuación Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) ha sido propuesta para sustituir a la actualmente recomendada Modification of Diet in Renal Disease (MDRD) para el cálculo de la tasa de filtrado glomerular (TFG), si bien no ha sido aún evaluada en la población general. Pacientes y Método: Estudio transversal de una muestra aleatoria de 858 individuos de la población general con edades entre 50–75 años sin enfermedad renal conocida. Comparación de la prevalencia de una TFG<60ml/min/1,73m2 calculada con las ecuaciones MDRD y CKD-EPI en toda la muestra y en el subgrupo de individuos normoalbuminúricos (cociente albúmina/creatinina<30mg/g). Resultados: Con la ecuación MDRD la mediana de la TFG (rango intercuartílico) en varones/mujeres fue de 63,3 (12,2)/56,7 (9,4) ml/min/1,73m2, y con la ecuación CKD-EPI 66,6 (14,2)/61,3 (11,6)ml/min/1,73m2, respectivamente. La prevalencia de una TFG baja en varones/mujeres fue del 35,2–68,5%, y del 25,1–45,7% con las ecuaciones MDRD y CKD-EPI, respectivamente. El grupo de mujeres normoalbuminúricas sin factores de riesgo para enfermedad renal crónica presentó la mayor reducción en la prevalencia de una TFG baja con la ecuación CKD-EPI. Sin embargo, la prevalencia en este grupo se mantuvo incluso más elevada que en el de los varones con diabetes, hipertensión o enfermedad cardiovascular. Conclusiones: Comparada con la ecuación MDRD, la ecuación CKD-EPI produce una importante reducción en la prevalencia de insuficiencia renal en individuos con diabetes, hipertensión, enfermedad cardiovascular, y en individuos sin factores de riesgo. La prevalencia de insuficiencia renal en mujeres normoalbuminúricas calculada con la ecuación CKD-EPI puede estar aún sobreestimada (AU)

Comparison of the MDRD and the CKD-EPI equations to estimate the glomerular filtration rate in the general population.

BACKGROUND AND OBJECTIVE: The Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI) equation has been proposed as a replacement for the Modification of Diet in Renal Disease (MDRD) equation to estimate the glomerular filtration rate, but this equation has not yet been evaluated in the general population. PATIENTS AND METHODS: Cross-sectional analysis of a random sample of 858 participants from the general population aged 50-75 years without known kidney disease. The prevalence of low eGFR (< 60 mL/min/1.73 m(2)) was assessed with the MDRD and the CKD-EPI equations in the overall sample and in normoalbuminuric individuals. RESULTS: With the MDRD equation the median eGFRs (interquartile range) in men/women were 63.3(12.2)/56.7(9.4)mL/min/1.73 m(2), and with the CKD-EPI equation 66.6(14.2)/61.3(11.6) mL/min/1.73 m(2). The prevalence of low eGFR in men/women was 35.2%/68.5% and 25.1%/45.7% with the MDRD and the CKD-EPI equations, respectively. Normoalbuminuric women without risk factors for CKD experienced the most pronounced reduction in the number of cases with low eGFR with the CKD-EPI equation. The prevalence of renal impairment in this subgroup still remained even greater than that in men with diabetes, hypertension, or cardiovascular disease. CONCLUSIONS: Compared with the MDRD, the CKD-EPI equation generates a substantial reduction in the prevalence of renal impairment in subjects with diabetes, hypertension, cardiovascular disease, and in subjects without risk factors. The prevalence of renal impairment in normoalbuminuric females may be still overestimated with the CKD-EPI equation.