Treatment of Chronic Heart Failure in Advanced Chronic Kidney Disease: The HAKA Multicenter Retrospective Real-World Study.

INTRODUCTION: Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units. METHODS: The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). RESULTS: Among 5,012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA, and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA, or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i. CONCLUSIONS: Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.

Intermediate steroid withdrawal after renal transplantation and anti-HLA antibodies (HLA-Abs) development / Retirada intermedia de esteroides después del trasplante renal y desarrollo de anticuerpos anti-HLA (Ac-antiHLA)

Introduction: Steroid withdrawal in renal transplantation is desirable to avoid their adverse effects. However, by decreasing the immunosuppression, could lead to an increased risk for the development of HLA-Abs. Objective: Evaluate the relationship between steroid withdrawal and development of HLA-Abs in renal transplantation. Methods: We analyzed sera by Luminex from 182 kidney transplants performed from 1998 to 2011, before and two years after transplantation. All the patients had a pretransplant PRA (panel reactive of antibodies) <20% by complement-dependent cytotoxicity (CDC) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF). We compared a group of steroid withdrawal at 7 months (group-I; n=130) and another control with non-withdrawal (group-II; n=52). Results: 22 patients (16.9%) in group-I and 11 patients in group-II (21.1%) had HLA-Abs after two years (pNS). Despite excluding patients with PRA >20%, we detected HLA-Abs pretransplant by Luminex in 11.5% of patients in both groups, of which, 66.6%, versus 53% (p 0.058), developed new specificities, with a similar percentage of donor specific antibodies (DSA) in both groups (33.33% vs 36.36%), pNS. In the subgroup without pretransplant HLA-Abs (group-I; n=115, group-II; n=45), 6.08% developed de novo HLA-Abs, being DSA 3.4% (Group-I) versus 7.69% in group II with 3.84% DSA (pNS). Conclusions: Steroid withdrawal at 7 months of renal transplantation does not entail a higher risk in terms of HLA-Abs development in patients without pretransplant HLA-Abs and treatment with tacrolimus and MMF, although larger studies are needed to confirm these findings (AU)

Introducción: La retirada de esteroides en el trasplante renal es deseable por sus efectos adversos, sin embargo, al disminuir la inmunosupresión podría conllevar un riesgo superior para el desarrollo de Ac-anti-HLA. Objetivo: Evaluar la relación entre la retirada de esteroides y el desarrollo de Ac-anti-HLA en el trasplante renal. Métodos: Se evaluaron los sueros por Luminex de 182 trasplantados renales desde 1998 a 2011, antes y a los 2 años del trasplante. Todos tenían un panel reactivo frente a anticuerpos (PRA)<20% pretrasplante por citotoxicidad dependiente de complemento y mantuvieron la inmunosupresión con tacrolimús y micofenolato mofetilo (MMF). Comparamos un grupo de retirada de esteroides a los 7 meses (grupo I; n=130) y otro de no retirada (grupo II; n=52). Resultados: 22 pacientes (16,9%) en el grupo I y 11 pacientes en el grupo II (21,1%) presentaban Ac-anti-HLA a los 2 años (pNS). A pesar de excluir a los pacientes con PRA>20%, detectamos Ac-anti-HLA pretrasplante por Luminex en el 11,5% de los pacientes en ambos grupos, de los cuales, desarrollaron nuevas especificidades el 66,6% del grupo Iy el 53% en el grupo II (p 0,058), con un similar porcentaje de anticuerpos donante específicos (DSA) (33,3% vs. 36,36%), pNS. En el subgrupo sin Ac-anti-HLA pretrasplante (grupo I; n=115; grupo II; n=45), el 6,08% desarrollaron Ac-anti-HLA de novo, siendo DSA el 3,4% (grupo-I) vs. 7,69% con DSA en el 3,84% (grupo-II), pNS. Conclusiones: La retirada de esteroides a los 7 meses del trasplante renal no conlleva un riesgo superior en términos de desarrollo de Ac-anti-HLA en aquellos pacientes sin anticuerpos pretrasplante y en tratamiento con tacrolimús y MMF, aunque se requieren estudios más amplios para confirmar estos hallazgos (AU)

Intermediate steroid withdrawal after renal transplantation and anti-HLA antibodies (HLA-Abs) development.

INTRODUCTION: Steroid withdrawal in renal transplantation is desirable to avoid their adverse effects. However, by decreasing the immunosuppression, could lead to an increased risk for the development of HLA-Abs. OBJECTIVE: Evaluate the relationship between steroid withdrawal and development of HLA-Abs in renal transplantation. METHODS: We analyzed sera by Luminex from 182 kidney transplants performed from 1998 to 2011, before and two years after transplantation. All the patients had a pretransplant PRA (panel reactive of antibodies) <20% by complement-dependent cytotoxicity (CDC) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF). We compared a group of steroid withdrawal at 7 months (group-I; n=130) and another control with non-withdrawal (group-II; n=52). RESULTS: 22 patients (16.9%) in group-I and 11 patients in group-II (21.1%) had HLA-Abs after two years (pNS). Despite excluding patients with PRA >20%, we detected HLA-Abs pretransplant by Luminex in 11.5% of patients in both groups, of which, 66.6%, versus 53% (p 0.058), developed new specificities, with a similar percentage of donor specific antibodies (DSA) in both groups (33.33% vs 36.36%), pNS. In the subgroup without pretransplant HLA-Abs (group-I; n=115, group-II; n=45), 6.08% developed de novo HLA-Abs, being DSA 3.4% (Group-I) versus 7.69% in group II with 3.84% DSA (pNS). CONCLUSIONS: Steroid withdrawal at 7 months of renal transplantation does not entail a higher risk in terms of HLA-Abs development in patients without pretransplant HLA-Abs and treatment with tacrolimus and MMF, although larger studies are needed to confirm these findings.

Comparación de los sistemas de clasificación del fracaso renal agudo en la sepsis / A comparison of acute kidney injury classification systems in sepsis

Antecedentes: Desde 2004 se han propuesto diversos criterios para definir y estadiar el fracaso renal agudo (FRA), sin embargo, no se conoce cuál de ellos debe ser empleado cuando se desarrolla FRA en el contexto de la sepsis grave. Objetivo: Valorar la capacidad predictiva de mortalidad en una cohorte de pacientes con sepsis de los distintos métodos de clasificación del FRA. Métodos: Estudio prospectivo de los pacientes>18 años ingresados en la Unidad de Cuidados Intensivos (UCI) de nuestro hospital desde abril de 2008 hasta septiembre de 2010 con shock séptico. La creatinina plasmática se determinó diariamente en UCI. Los pacientes se clasificaron de forma retrospectiva según las clasificaciones RIFLE, AKIN, KDIGO y cinética de la creatinina (CK). Resultados: El porcentaje de pacientes que desarrolló FRA según cada clasificación fue: 74,3% RIFLE; 81,7% AKIN; 81,7% KDIGO y 77,5% CK. Cada estadio de FRA por RIFLE (OR 1,452; p=0,003), por AKIN (OR 1,349; p=0,028) y por KDIGO (OR 1,452; p=0,006) se relacionaba de forma independiente con la mortalidad intrahospitalaria, pero no por CK (OR 1,188; p=0,148). Conclusiones: Un porcentaje elevado de pacientes con sepsis grave desarrolla FRA que se puede clasificar según los distintos métodos propuestos. Los estadios de las clasificaciones RIFLE, AKIN y KDIGO se relacionan con un mayor riesgo de muerte intrahospitalaria. Por el contrario, la nueva definición de CK no se relaciona con una mayor mortalidad y no se debería usar en estos pacientes con sepsis grave sin confirmar su utilidad en estudios posteriores (AU)

Background: Since 2004, various criteria have been proposed to define and stage acute kidney injury (AKI). Nevertheless, fixed criteria for assessing severe sepsis-related AKI have not yet been established. Objectives: To assess the ability of the different AKI classification methods to predict mortality in a cohort of patients with sepsis. Methods: A prospective study of patients>18 years with septic shock admitted to the intensive care unit (ICU) of our hospital from April 2008 to September 2010 was conducted. Plasma creatinine levels were measured daily in the ICU. Patients were classified retrospectively according to RIFLE, AKIN, KDIGO and creatinine kinetics (CK) criteria. Results: The AKI rate according to the different criteria was 74.3% for RIFLE, 81.7% for AKIN, 81.7% for KDIGO and 77.5% for CK. AKI staging by RIFLE (OR 1.452, P=.003), AKIN (OR 1.349, P=.028) and KDIGO criteria (OR 1.452,P=.006), but not CK criteria (OR 1.188, P=.148) were independently related to in-hospital mortality. Conclusions: A high rate of patients with severe sepsis developed AKI, which can be classified according to different criteria. Each stage defined by RIFLE, AKIN and KDIGO related to a higher risk of in-hospital mortality. In contrast, the new CK criteria did not relate to higher mortality in patients with severe sepsis and this classification should not be used in these patients without further studies assessing its suitability (AU)

A comparison of acute kidney injury classification systems in sepsis. / Comparación de los sistemas de clasificación del fracaso renal agudo en la sepsis.

BACKGROUND: Since 2004, various criteria have been proposed to define and stage acute kidney injury (AKI). Nevertheless, fixed criteria for assessing severe sepsis-related AKI have not yet been established. OBJECTIVES: To assess the ability of the different AKI classification methods to predict mortality in a cohort of patients with sepsis. METHODS: A prospective study of patients>18 years with septic shock admitted to the intensive care unit (ICU) of our hospital from April 2008 to September 2010 was conducted. Plasma creatinine levels were measured daily in the ICU. Patients were classified retrospectively according to RIFLE, AKIN, KDIGO and creatinine kinetics (CK) criteria. RESULTS: The AKI rate according to the different criteria was 74.3% for RIFLE, 81.7% for AKIN, 81.7% for KDIGO and 77.5% for CK. AKI staging by RIFLE (OR 1.452, P=.003), AKIN (OR 1.349, P=.028) and KDIGO criteria (OR 1.452, P=.006), but not CK criteria (OR 1.188, P=.148) were independently related to in-hospital mortality. CONCLUSIONS: A high rate of patients with severe sepsis developed AKI, which can be classified according to different criteria. Each stage defined by RIFLE, AKIN and KDIGO related to a higher risk of in-hospital mortality. In contrast, the new CK criteria did not relate to higher mortality in patients with severe sepsis and this classification should not be used in these patients without further studies assessing its suitability.

Sesión de hemodiálisis: la tormenta perfecta para la calcificación vascular / Haemodialysis session: The perfect storm for vascular calcification

Introducción: La calcificación vascular (CV) asociada a la enfermedad renal crónica (ERC) es un fenómeno estrechamente ligado a las alteraciones en el metabolismo mineral óseo. Existen muchos factores implicados, entre ellos los fármacos empleados en el tratamiento de la ERC. Algunos estudios in vitro señalan que las alteraciones electrolíticas y ácido básicas que tienen lugar durante la sesión de hemodiálisis (HD) pueden jugar un papel clave en el proceso de CV. Métodos: Analizamos las alteraciones electrolíticas y ácido-básicas que tienen lugar durante la sesión de HD en 26 pacientes, empleando de forma aleatorizada concentraciones de calcio en el líquido de diálisis de 1,25 o 1,5 mM. Resultados: En todos los pacientes, independientemente del baño de calcio empleado, se produce una ganancia de calcio. En el grupo de pacientes dializados con baño de calcio 1,5mM, el 100% finaliza la sesión con valores de calcio sérico > 1,3 mM, mientras que en el de 1,25mM, esto solo ocurre en el 15%. Al inicio de la sesión, esta ganancia de calcio coincide con niveles de fósforo aún no controlado. Además, en todos los pacientes se observa una alcalinización progresiva: el 50% finaliza la sesión con cifras de bicarbonato > 30mM y el 23% con pH> 7,5. Conclusiones: Durante la sesión de HD se producen cambios electrolíticos y ácido-básicos inductores de CV: ganancia de calcio y alcalinización en presencia de fósforo sérico inicialmente elevado. Son necesarios estudios con modelos cinéticos de ganancia de calcio y alcalinización diferentes a los actuales (AU)

Introduction: Vascular calcification (VC) associated to chronic kidney disease (CKD) is a complex phenomenon closely related to mineral bone metabolism disorders. Many are the factors implicated, as the drugs used in the treatment of CKD. Some in vitro studies suggest that electrolyte and acid-base disorders induced by hemodialysis (HD) may play a key role in VC. Methods: We analyzed electrolyte and acid-base disorders that occur during an HD session in 26 patients randomly assigned to 1,25 mM or 1,5 mM calcium bath. Results: There is a calcium load in all the patients, independently of calcium bath concentration or basal serum calcium levels. At the end of the session, 100% of the patients dialyzed with 1,5mMcalcium bath have calcium serum levels > 1,3 mM. However, this only occurs in 15% of the patients dialysed with 1,25 mM calcium bath. During this calcium load, phosphorus levels persist uncontrolled. Besides, there is a progressive alkalinization in all the patients. In the end of the session 50% have serum bicarbonate > 30 mM and 23% pH > 7,5. Conclusions: During HD sessions occur electrolyte and acid-base disorders that induce VC: Calcium load and alkalization in presence of elevated phosphorus levels. It is necessary to perform studies with kinetic models of calcium load and alkalinization different from the actual ones (AU)

Sodium Excretion Pattern at 1 Year After Kidney Transplantation and High Blood Pressure.

BACKGROUND: High blood pressure (BP) after kidney transplantation decreases graft and patient survival. There is a causal relationship between high salt intake and increased BP in the general population, but the role of salt intake on post-transplant hypertension remains controversial. The aims of our study were to determine the pattern of salt intake in the first year post-transplantation and its influence on BP in our kidney transplant population. MATERIAL AND METHODS: We selected 270 deceased-donor kidney transplant recipients with graft survival longer than 1 year and at least 1 adequate 24-h urinary sodium excretion measurement at the first year visit in order to be included in the analysis. RESULTS: Some 87.0% patients had a sodium excretion (mean 165±73 mmol/day) higher than recommended. Male and younger recipients with a high body mass index had a higher sodium excretion. Among other variables, sodium excretion was independently related to higher systolic (b 3.529 per 100 mmol/day, 95%CI 0.725-6.334, p=0.014) and diastolic (b 1.866 per 100 mmol/day, 95%CI 0.237-3.496, p=0.025) BP. CONCLUSIONS: A high percentage of kidney transplant recipients have salt intake higher than recommended, contributing to increased BP. Measurement of 24-h urinary sodium excretion identifies non-compliant kidney transplant recipients who need intervention to improve BP control and graft outcome.

Haemodialysis session: the perfect storm for vascular calcification.

INTRODUCTION: Vascular calcification (VC) associated to chronic kidney disease (CKD) is a complex phenomenon closely related to mineral bone metabolism disorders. Many are the factors implicated, as the drugs used in the treatment of CKD. Some in vitro studies suggest that electrolyte and acid-base disorders induced by hemodialysis (HD) may play a key role in VC. METHODS: We analyzed electrolyte and acid-base disorders that occur during an HD session in 26 patients randomly assigned to 1,25 mM or 1,5 mM calcium bath. RESULTS: There is a calcium load in all the patients, independently of calcium bath concentration or basal serum calcium levels. At the end of the session, 100% of the patients dialyzed with 1,5 mM calcium bath have calcium serum levels > 1,3 mM. However, this only occurs in 15% of the patients dialysed with 1,25 mM calcium bath. During this calcium load, phosphorus levels persist uncontrolled. Besides, there is a progressive alkalinization in all the patients. In the end of the session 50% have serum bicarbonate > 30 mM and 23% pH > 7,5. CONCLUSIONS: During HD sessions occur electrolyte and acid-base disorders that induce VC: Calcium load and alkalization in presence of elevated phosphorus levels. It is necessary to perform studies with kinetic models of calcium load and alkalinization different from the actual ones.

Effect of calcium acetate/magnesium carbonate in the treatment of hyperphosphataemia in dialysis patients in real clinical practice. One year follow up / Efectos del acetato cálcico/carbonato magnésico en el tratamiento de la hiperfosfatemia en pacientes en diálisis en la práctica clínica real. Seguimiento durante un año

Background: This observational study was conducted to investigate the use and effectiveness of calcium acetate/magnesium carbonate (CaMg) in the treatment of hyperphosphataemia in dialysis patients in real-world clinical practice. Methods: 120 adult CKD patients on dialysis who received CaMg alone or in combination with other phosphate binders were followed-up for 3-12 months. Serum phosphorus, calcium, magnesium, parathyroid hormone and albumin concentration was measured at baseline and after 3, 6 and 12 months respectively. In addition, CaMg dosage, use of concurrent phosphate binders, vitamin D and cinacalcet was documented. Patients were evaluated in 2 subgroups - CaMg alone (n=79) vs. CaMg + concurrent phosphate binder (n=41). Results: In both subgroups serum phosphorus levels decreased significantly from baseline at 3, 6 and 12 months of CaMg treatment. The percentage achievement of recommended serum phosphorus targets improved after CaMg initiation. At month 6, a total of 78% were within the Kidney Disease Outcomes Quality Initiative (K/DOQI) target range. Total corrected serum calcium increased during CaMg treatment, but mildly exceeded the upper limit of normal in three patients only. Asymptomatic significant increases in magnesium (p<0.001) were observed in the monotherapy group at 3, 6 and 12 months. A total of 80 patients (67%) experienced episodes of mild hypermagnesaemia (>2.6mg/mL, 1.05mmol/L). Conclusions: This analysis of current clinical practice shows that - consistent with findings from a randomised controlled trial - CaMg treatment leads to marked improvement in serum phosphorus levels, helping patients in trying to achieve K/DOQI and KDIGO (Kidney Disease Improving Global Outcome) targets (AU)

Antecedentes: Este estudio observacional se llevó a cabo para investigar el uso y la efectividad, en la práctica clínica real, del acetato cálcico/carbonato magnésico (CaMg) en el tratamiento de la hiperfosfatemia en pacientes en diálisis. Métodos: Se realizó un seguimiento durante 3-12 meses en 120 pacientes adultos con enfermedad crónica renal en tratamiento con diálisis que recibían monotratamiento con CaMg o en combinación con otros quelantes del fósforo. Se midieron en suero los valores de fósforo, calcio, magnesio, hormona paratiroidea y concentración de albúmina a nivel basal y tras 3, 6 y 12 meses, respectivamente. Además, se documentó la dosis de CaMg, el uso de quelantes de fósforo concomitantes, la vitamina D y el cinacalcet. Los pacientes se dividieron en 2 subgrupos: aquellos a los que solo se les administraba CaMg (n=79) frente a los que recibían CaMg y un quelante de fósforo concomitante (n=41). Resultados: En ambos subgrupos, los niveles de fósforo sérico disminuyeron de forma significativa, con respecto a los basales, a los 3, 6 y 12 meses de tratamiento con CaMg. El porcentaje de logro de los niveles recomendados de fósforo sérico mejoró tras iniciar el tratamiento con CaMg. El mes 6, un total del 78% se encontraba dentro de las recomendaciones objetivo de Calidad de los Resultados de la Insuficiencia Renal (K/DOQI). El calcio sérico total corregido aumentó durante el tratamiento con CaMg, pero superaba levemente los límites superiores normales solo en tres pacientes. Asimismo, se observaron incrementos significativos del magnesio asintomáticos (P<0,001) en el grupo de monoterapia a los 3, 6 y 12 meses. Un total de 80 pacientes (67%) sufrieron episodios de hipermagnesemia leve (>2,6 mg/mL, 1,05 mmol/L). Conclusiones: El presente análisis de la práctica clínica habitual, en consonancia con los datos obtenidos de un ensayo aleatorizado controlado, demuestra que el tratamiento con CaMg mejora de forma considerable los niveles de fósforo sérico y ayuda a los pacientes a conseguir los objetivos K/DOQI y KDIGO (mejora de los resultados globales en la enfermedad renal) (AU)

Effect of calcium acetate/magnesium carbonate in the treatment of hyperphosphataemia in dialysis patients in real clinical practice. One year follow up.

BACKGROUND: This observational study was conducted to investigate the use and effectiveness of calcium acetate/magnesium carbonate (CaMg) in the treatment of hyperphosphataemia in dialysis patients in real-world clinical practice. METHODS: 120 adult CKD patients on dialysis who received CaMg alone or in combination with other phosphate binders were followed-up for 3-12 months. Serum phosphorus, calcium, magnesium, parathyroid hormone and albumin concentration was measured at baseline and after 3, 6 and 12 months respectively. In addition, CaMg dosage, use of concurrent phosphate binders, vitamin D and cinacalcet was documented. Patients were evaluated in 2 subgroups – CaMg alone (n=79) vs. CaMg + concurrent phosphate binder (n=41). RESULTS: In both subgroups serum phosphorus levels decreased significantly from baseline at 3, 6 and 12 months of CaMg treatment. The percentage achievement of recommended serum phosphorus targets improved after CaMg initiation. At month 6, a total of 78% were within the Kidney Disease Outcomes Quality Initiative (K/DOQI) target range. Total corrected serum calcium increased during CaMg treatment, but mildly exceeded the upper limit of normal in three patients only. Asymptomatic significant increases in magnesium (p<0.001) were observed in the monotherapy group at 3, 6 and 12 months. A total of 80 patients (67%) experienced episodes of mild hypermagnesaemia (>2.6mg/mL, 1.05mmol/L). CONCLUSIONS: This analysis of current clinical practice shows that – consistent with findings from a randomised controlled trial – CaMg treatment leads to marked improvement in serum phosphorus levels, helping patients in trying to achieve K/DOQI and KDIGO (Kidney Disease Improving Global Outcome) targets.