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.

Diastolic dysfunction is an independent predictor for cardiovascular events after an acute kidney injury.

BACKGROUND AND AIM: Acute kidney injury (AKI) conditions several short- and long-term complications. The aim of the present study was to analyse the impact of cardiac function and structure in the cardiovascular prognosis after an in-hospital AKI episode. MATERIAL AND METHODS: This is an observational retrospective cohorts study including all in-hospital AKI episodes in 2013 and 2014 in our centre. At baseline, epidemiological values, comorbidities and echocardiography parameters were collected. During a follow-up of 49 ±â€¯28 months, cardiovascular events (CVE) were collected, and associated factors were analysed. RESULTS: 1255 patients were included (55% male, age 75 ±â€¯13 years). Of the 676 (54%) that had a previous echocardiogram, 46% had left ventricular hypertrophy, 38% pulmonary hypertension, 38% diastolic dysfunction and 22% systolic dysfunction. During the follow-up, 484 (39%) developed a CVE. Associated factors to VCE were male sex, age, diabetes mellitus, hypertension, dyslipidemia, coronary heart disease, heart failure, atrial fibrillation, neoplasia and chronic kidney disease (also, glomerular filtration rate at baseline and after the AKI episode). Survival curves demonstrated that all the echocardiographic parameters were associated to CVE. An adjusted Cox regression model showed that age (HR 1.017), diabetes (HR 1.576) and diastolic dysfunction (HR 1.358) were independent predictors for CVE. CONCLUSION: Diastolic dysfunction is an independent predictor for long-term cardiovascular events after an in-hospital acute kidney injury episode.

La disfunción diastólica es un predictor independiente de eventos cardiovasculares tras un fracaso renal agudo / Diastolic dysfunction is an independent predictor for cardiovascular events after an acute kidney injury

Antecedente y objetivo: El desarrollo de un fracaso renal agudo (FRA) condiciona complicaciones a corto, medio y largo plazo. El objetivo de nuestro estudio fue analizar el impacto de las alteraciones cardiacas en el pronóstico cardiovascular de pacientes que presentan un episodio de FRA. Materiales y métodos: Realizamos un estudio observacional de cohortes retrospectivo incluyendo a todos los pacientes con FRA en 2013 y 2014. Basalmente recogimos variables epidemiológicas, comorbilidades y parámetros ecocardiográficos. Seguimos a los pacientes tras el ingreso durante una media de 49 ± 28 meses, recogiendo la incidencia de eventos cardiovasculares (ECV) y los factores asociados a los mismos. Resultados: Se incluyeron 1.255 pacientes (55% varones, edad 75 ± 13 años). De los 676 (54%) pacientes que disponían de un ecocardiograma previo, el 46% tenían hipertrofia de ventrículo izquierdo, el 38% hipertensión pulmonar, el 38% disfunción diastólica y el 22% disfunción sistólica. Tras la hospitalización por FRA, 484 (39%) tuvieron un ECV. Los factores asociados a presentar un ECV fueron el sexo (varón), la edad, diabetes mellitus, hipertensión arterial, dislipidemia, cardiopatía isquémica, insuficiencia cardiaca, fibrilación auricular, neoplasia previa y enfermedad renal crónica (y el filtrado glomerular estimado basal y tras el FRA). El análisis de supervivencia demostró que todos los parámetros ecocardiográficos se asociaban a ECV. Un modelo de regresión de Cox ajustado demostró que la edad (HR 1,017), la diabetes mellitus (HR 1,576) y la disfunción diastólica (HR 1,358) eran predictores independientes de ECV. Conclusiones: La disfunción diastólica es un predictor independiente de ECV a largo plazo tras un episodio hospitalario de FRA. (AU)

Background and aim: Acute kidney injury (AKI) conditions several short- and long-term complications. The aim of the present study was to analyse the impact of cardiac function and structure in the cardiovascular prognosis after an in-hospital AKI episode. Materials and methods: This is an observational retrospective cohorts study including all in-hospital AKI episoes in 2013 and 2014 in our centre. At baseline, epidemiological values, comorbidities and echocardiography parameters were collected. During a follow-up of 49 ± 28 months, cardiovascular events (CVEs) were collected, and associated factors were analysed. Results: 1255 patients were included (55% male, age 75 ± 13 years). Of the 676 (54%) that had a previous echocardiogram, 46% had left ventricular hypertrophy, 38% pulmonary hypertension, 38% diastolic dysfunction and 22% systolic dysfunction. During the follow-up, 484 (39%) developed a CVE. Associated factors to CVE were male sex, age, diabetes mellitus, hypertension, dyslipidemia, coronary heart disease, heart failure, atrial fibrillation, neoplasia and chronic kidney disease (also, glomerular filtration rate at baseline and after the AKI episode). Survival curves demonstrated that all the echocardiographic parameters were associated to CVE. An adjusted Cox regression model showed that age (HR 1.017), diabetes (HR 1.576) and diastolic dysfunction (HR 1.358) were independent predictors for CVE. Conclusion: Diastolic dysfunction is an independent predictor for long-term CVEs after an in-hospital AKI episode. (AU)

Efecto regulador de paricalcitol sobre parámetros inflamatorios, fibróticos y anticalcificantes en el paciente con enfermedad renal crónica. Más allá de la regulación de la enfermedad óseo-mineral / Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patiente. Far beyond mineral bone disease regulation

ANTECEDENTES: La principal causa de morbimortalidad en el paciente con enfermedad renal crónica (ERC) es la cardiovascular. La inflamación y las alteraciones en el metabolismo óseo-mineral en estos pacientes conllevan aumento del riesgo cardiovascular. OBJETIVOS: Valorar el papel de paricalcitol sobre distintos parámetros séricos relacionados con inflamación, fibrosis y enfermedad óseo-mineral en la ERC. MATERIAL Y MÉTODOS: Estudio prospectivo, no controlado en 46 pacientes con ERC estadios III-V sin diálisis, con niveles elevados de paratohormona, según su estadio de ERC, por lo que se introdujo tratamiento con el análogo de vitamina D paricalcitol. Durante 4 meses de tratamiento valoramos los parámetros clásicos y novedosos del metabolismo óseo-mineral en suero (calcio, fósforo, paratohormona, factor de crecimiento fibroblástico-23 [FGF-23], Klotho y calcidiol) y parámetros relacionados con el proceso de inflamación-fibrosis y anticalcificantes (interleucina-6 y 10, factor de necrosis tumoral alfa [TNF-a], factor de crecimiento transformante beta [TGF-b], proteína ósea morfogénica-7 [BMP-7], y fetuína-A). RESULTADOS: Tras el uso de paricalcitol los niveles de Klotho aumentaron (p = 0,001) y los de FGF-23 se mantuvieron estables al igual que los de calcio y fósforo; calcidiol aumentó de forma significativa (p = 0,010) y paratohormona descendió (p = 0,002). Los parámetros de inflamación, fibrosis y calcificación mostraron una regulación benigna con descenso significativo de interleucina-6 (p = 0,001), TNF-alfa (p = 0,005) y TGF-β (p = 0,001) y aumento de BMP-7 (p = 0,001), fetuína-A (p = 0,001) e interleucina-10 (p = 0,001). El filtrado glomerular y la proteinuria se mantuvieron estables. CONCLUSIONES: El tratamiento con paricalcitol en el paciente renal sin diálisis parece ser beneficioso en la regulación de los parámetros inflamatorios y anticalcificantes, preservando la función renal y el eje óseo-mineral. Los marcadores elegidos en nuestro estudio podrían indicarnos un efecto positivo de paricalcitol a nivel vascular

BACKWARD: Cardiovascular events are the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Inflammation and mineral-bone disorder are pathological conditions that have been associated with an increased cardiovascular risk. OBJECTIVE: Show paricalcitol regulation overinflammatory, fibrotic and mineral disorder parameters in CKD. MATERIAL AND METHODS: Prospective Study in 46 CKD stages III-V patients without dialysis patients whith elevated parathormone in which we introduced paricalcitol. We evaluated classic and newest mineral and bone metabolism serum parameters (calcium, phosphorus, parathormone, fibroblast growth factor-23 [FGF-23], Klotho, calcidiol), inflammatory-fibrosis and anticalcifying parameters (interleukin-6 and 10, tumor necrosis factor-a [TNF- alfa], transforming growth factor-b [TGF-β],bone morphogenic protein-7 [BMP-7] and fetuin-A) for four months. RESULTS: At the end of study soluble Klotho increased (p = .001), FGF-23 remained stable, calcium and phosphorus levels were not increased, calcidiol increased (p = .010) and PTH decreased (p = .002). Inflammation-fibrosis and calcification parameters showed positive regulation after paricalcitol treatment: interleukin-6 decreased significantly (p = .001) and also TNF-alfa did (p = .005), on the contrary, interleukin-10 and fetuin-A increased (p = .001 for both). Anti-fibrosis marker BMP-7 increased (p = .001) and TGF-b decreased (p = .001). We did not find significant changes in renal function. CONCLUSIONS: Paricalcitol treatment might be profitable in regulating inflammatory and anticalcificant parameters, unmodified calcium or phosphorus seric levels and preserving kidney function in renal patients with no dialysis. Our selected parameters could indicate paricalcitol effects in mineral and endothelial disorder related to renal disease

Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patiente. Far beyond mineral bone disease regulation. / Efecto regulador de paricalcitol sobre parámetros inflamatorios, fibróticos y anticalcificantes en el paciente con enfermedad renal crónica. Más allá de la regulación de la enfermedad óseo-mineral.

BACKWARD: Cardiovascular events are the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Inflammation and mineral-bone disorder are pathological conditions that have been associated with an increased cardiovascular risk. OBJECTIVE: Show paricalcitol regulation overinflammatory, fibrotic and mineral disorder parameters in CKD. MATERIAL AND METHODS: Prospective Study in 46 CKD stages III-V patients without dialysis patients whith elevated parathormone in which we introduced paricalcitol. We evaluated classic and newest mineral and bone metabolism serum parameters (calcium, phosphorus, parathormone, fibroblast growth factor-23 [FGF-23], Klotho, calcidiol), inflammatory-fibrosis and anticalcifying parameters (interleukin-6 and 10, tumor necrosis factor-a [TNF- α], transforming growth factor-b [TGF-ß],bone morphogenic protein-7 [BMP-7] and fetuin-A) for four months. RESULTS: At the end of study soluble Klotho increased (p=.001), FGF-23 remained stable, calcium and phosphorus levels were not increased, calcidiol increased (p=.010) and PTH decreased (p=.002). Inflammation-fibrosis and calcification parameters showed positive regulation after paricalcitol treatment: interleukin-6 decreased significantly (p=.001) and also TNF-α did (p=.005), on the contrary, interleukin-10 and fetuin-A increased (p=.001 for both). Anti-fibrosis marker BMP-7 increased (p=.001) and TGF-b decreased (p=.001). We did not find significant changes in renal function. CONCLUSIONS: Paricalcitol treatment might be profitable in regulating inflammatory and anticalcificant parameters, unmodified calcium or phosphorus seric levels and preserving kidney function in renal patients with no dialysis. Our selected parameters could indicate paricalcitol effects in mineral and endothelial disorder related to renal disease.

Mecanismos inflamatorios y fibróticos en la enfermedad renal. Protagonistas y terapéutica / Inflammatory and fibrotic process in kidney disease. Protagonists and therapy

La enfermedad renal es un problema de salud pública por su incidencia, prevalencia y morbimortalidad. La inflamación y fibrosis son el motor de toda alteración del daño renal, independientemente de su origen. El proceso inflamatorio y fibrótico se caracteriza por infiltración de células inflamatorias, liberación de citoquinas, activación de fibroblastos, de señales químicas y vías de señalización. Este proceso conlleva la generación de células efectoras productoras de matriz extracelular o de complejos de ataque que desemboca en el daño orgánico. Ninguna terapia ha demostrado eficacia total frente al daño inflamatorio o fibrótico. Muchos fármacos, en desarrollo experimental, ejercen su inmunomodulación a través de la regulación de la actividad de muchos tipos de células inmunes y presentan un perfil antiinflamatorio y fibrótico. El objetivo es ser conocedores de la importancia de los procesos que son capaces de provocar el proceso inflamatorio y fibrótico dado que podría tratarse de marcadores diagnósticos y dianas terapéuticas

Chronic kidney disease is a serious public health problem, due to its high incidence and prevalence, as well as its significant morbidity and mortality. Inflammation and fibrosis are the final step in renal failure. The inflammatory and fibrotic process is highlighted by infiltration by inflammatory cells, cytokine release, fibroblast accumulation, and activation of numerous chemical signals. Those processes involve the generating of immunomodulatory cells that produce an extracellular matrix and attack complex, leading to organ damage. There is no an effective therapy against fibrotic and inflammatory damage. There are different drugs that have shown to be beneficial over inflammation and fibrosis in experimental and in vitro studies. The aim is to be aware of the processes that are able to trigger fibrosis and inflammation, given that they could be used as diagnostic markers and therapeutic targets

Tratamiento congestivo: diuréticos, resistencia diurética y alternativas Papel de la ultrafiltración / Tratamento congestivo: diuréticos, resistência diurética e alternativas Papel da ultrafiltração / Congestive treatment: diuretic treatment, diuretic resistance and alternatives Ultrafiltration role

Los pacientes con insuficiencia cardíaca descompensada presentan un estado congestivo. La inmensa mayoría de las veces es debido a la activación de mecanismos neurohormonales que provocan la retención de sodio y agua a nivel renal. Esta activación y la congestión pueden devenir en la alteración de la función renal (síndrome cardio-renal). El tratamiento de la congestión se basa en el uso de diuréticos, pero la inmensa mayoría de estos pacientes presentan resistencia a los mismos, además de sufrir diferentes efectos secundarios por su uso, como las alteraciones hidroelectrolíticas. Terapias como la ultrafiltración o la diálisis peritoneal se han valorado en el tratamiento de la insuficiencia cardíaca congestiva. Nuestro objetivo es hacer una aproximación al lector de las alternativas al tratamiento diurético en el paciente congestivo, centrándonos, prioritariamente, en la ultrafiltración.

Patients with decompensated heart failure have a congestive state. Volume overloaded state is due to neurohormonal mechanisms activation that cause the retention of sodium and water by the kidney. This activation and congestion can lead to impaired renal function (cardio-renal syndrome). Congestive treatment is based on use of diuretics but the vast majority of these patients have diuretic resistance, as well as suffering from different side effects due to their use such as hydroelectrolytic alterations. Therapies such ultrafiltration or peritoneal dialysis have been evaluated in the treatment of congestive heart failure. Our objective is to make an approximation of other therapeutic strategies specially on ultrafiltration to resolve congestive state.

Pacientes com insuficiência cardíaca descompensada apresentam um estado congestivo. A grande maioria é devido à ativação de mecanismos neuro-hormonais que causam a retenção de sódio e água nos rins. Essa ativação e congestão podem resultar em comprometimento da função renal (síndrome cardio-renal). O tratamento da congestão baseia-se no uso de diuréticos, mas a grande maioria destes pacientes têm a mesma resistência, e sofrem de diversos efeitos colaterais por utilização, como perturbações electrolíticas. Terapias como ultrafiltração ou diálise peritoneal foram avaliadas no tratamento da insuficiência cardíaca congestiva. Nosso objetivo é aproximar o leitor das alternativas ao tratamento diurético no paciente congestivo, enfocando, principalmente, a ultrafiltração.

Dialysis catheter related bacteriemia by Gordonia rubropertincta and Sputi in two hemodialysis patients / Bacteriemia relacionada por Gordonia rubropertincta y Sputi en 2 pacientes en hemodiálisis

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Enfermedad óseo mineral relacionada con la enfermedad renal crónica: Klotho y FGF23; implicaciones cardiovasculares / Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications

Una de las principales causas de morbimortalidad en el paciente con enfermedad renal crónica es la cardiovascular. La inflamación y las alteraciones en el metabolismo óseo mineral son una condición patológica que conlleva aumento del riesgo cardiovascular en la enfermedad renal crónica. Los parámetros bioquímicos clásicos del metabolismo óseo mineral como fósforo, calcio, vitamina D y PTH tienen una implicación muy conocida en el riesgo cardiovascular. Los nuevos marcadores, FGF23 y klotho, también podrían estar implicados en la enfermedad cardiovascular (AU)

Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease. Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease. The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known. The newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease (AU)

Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications. / Enfermedad óseo mineral relacionada con la enfermedad renal crónica: Klotho y FGF23; implicaciones cardiovasculares.

Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease. Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease. The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known. The newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease.

Arritmia cardiaca grave por hipopotasemia. Influencia de las sustancias diuréticas / Severe arrhythmia due to hypokalemia. Influence from diuretic substances

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