Paloma Gil

Long-Term Efficacy and Safety of Protease Inhibitor Switching to Nevirapine in HIV-Infected Patients with Undetectable Virus Load

BACKGROUND Simplified highly active antiretroviral therapy (HAART) regimens are becoming widely used, particularly as a result of the side effects of and difficult compliance with protease inhibitor (PI) therapy. However, the long-term efficacy of HAART has not been properly assessed. METHODS We performed a prospective study of 110 patients infected with human immunodeficiency virus type 1 (HIV-1) with undetectable virus load who discontinued PI therapy and initiated therapy with nevirapine without changing nucleoside analogues. Reasons for switching were treatment simplification (45%), lipodystrophy (24%), renal problems (23%), and dyslipidemia (8%). HIV-1 load, CD4 cell count, and fasting biochemistry profiles were performed at the time of switching (baseline) and every 3-4 months thereafter. The aim of the study was to evaluate the long-term efficacy and safety of this combination. RESULTS Sixty-eight patients (61.8%) had a duration of follow-up of 3 years. The mean increase in the CD4 cell count after 3 years was 90 cells/microL (13.8% from baseline). Virus loads remained undetectable in all patients but 9 (8.2%). Triglyceride levels dramatically improved at 12 months (a 75% decrease; P<.02) and remained statistically significant over time (P<.04). The same occurred with serum cholesterol levels: there was an initial reduction of 25% (P<.02) and at the end of the follow-up period (P<.015). However, at the long-term evaluation, complete normalization of mean serum cholesterol and triglyceride levels could not be achieved. Sixteen patients (14.5%) had to stop therapy as a result of nevirapine-associated side effects. CONCLUSIONS The switching of a PI to nevirapine is a safe and well-tolerated option for maintaining long-term virological suppression and immunological control. Three years after starting nevirapine therapy, rates of hypercholesterolemia and hypertriglyceridemia improved, although normal cholesterol and triglyceride values were not achieved.

Cardio-renal insufficiency : the search for management strategies

Purpose of reviewThis review focuses on the pathophysiology and treatment of an increasingly common entity, cardio-renal insufficiency. Cardio-renal insufficiency is more than a simultaneous cardiac and renal disease. Patients with this condition live within a fragile equilibrium challenged by the interaction of profibrogenic, atherosclerotic, neurohumoral, and other less known factors. Regarding therapy, the avoidance of oscillations between overfilled-decompensated and emptied-overtreated states becomes of critical importance. Particular focus should be paid to personalized treatment, adjusted according to heart and kidney reserve, the predictable complications of therapy, prevention of decompensations, simple measures-based follow-up and alternative procedures. Recent findingsRecent studies have established the important repercussions of unbalanced renal function on cardiovascular prognosis. In the heart failure setting, trials involving extensive cohorts of ageing or comorbidity-affected patients are presently under way. Special attention should be paid to recognize the presence of renal failure coexisting with heart failure, especially in patients with deceivingly near-normal plasma creatinine. Formulae to predict creatinine clearance are being increasingly incorporated into daily clinical practice. Disturbed renal function is an underappreciated prognostic factor in heart failure, and renal failure is frequently viewed as a relative contraindication to some proven efficacious therapies. SummaryCardio-renal insufficiency is an emerging entity, with affected individuals surviving with extreme degrees of simultaneous heart failure and renal failure. Management of the condition is an intellectually demanding process. Crucial to this management is extensive medical expertise and an in-depth understanding of the particular renal, haemodynamic and internal milieu equilibrium of the patients.

Anemia en la insuficiencia cardiaca: fisiopatología, patogenia, tratamiento e incógnitas

Aunque la anemia ha pasado a ocupar un plano relevante en la concepcion patogenica actual de la insuficiencia cardiaca (IC), se trata aun de una entidad rodeada de incognitas. La prevalencia de anemia y su importancia clinica en la poblacion con IC son muy elevadas. Sin embargo, no se han establecido aun con certeza suficiente los objetivos de tratamiento de la anemia en la poblacion con IC. El presente trabajo revisa aspectos clinicos y fisiopatologicos de esta forma particular de anemia, con especial atencion a los mecanismos celulares y moleculares de regulacion, y sus implicaciones en el tratamiento.

Insuficiencia combinada cardiorrenal: una clave evolutiva y terapéutica en el fallo cardíaco

La importancia de la enfermedad cardiovascular como primera causa de morbimortalidad en nuestro medio justifica el extraordinario esfuerzo realizado en la investigación de su etiopatogenia, pronóstico y tratamiento. Dentro de este marco, en los últimos años se ha tomado conciencia progresiva del papel de la insuficiencia renal (IR) en el pronóstico global de las enfermedades cardiovasculares1. La IR, en grados diferentes de severidad, acompaña de forma extremadamente frecuente a la insuficiencia cardíaca (IC) y en trabajos recientes se considera que puede predecir la mortalidad en la IC congestiva con mayor exactitud que la fracción de eyección o la clasificación de la New York Heart Association2. En este número de REVISTA ESPAÑOLA DE CARDIOLOGÍA, Grigorian-Shamagian et al3 analizan el papel de la IR como factor predictivo de mortalidad por IC. Sus datos, aunque limitados a la población con ingreso hospitalario, contienen una serie de aportaciones de interés respecto a un tema que ocupa en la actualidad un plano relevante de atención. En primer lugar, se trata de una casuística española que analiza un número elevado de pacientes (n = 552). Segundo, a diferencia de otras series centradas casi exclusivamente en el fallo sistólico, este estudio examina tanto los casos con función sistólica deprimida (FS-D) como preservada (FSP). Los resultados proporcionan información útil desde el punto de vista clínico, que subraya la importancia de la IR en el pronóstico y la evolución de la IC. ¿Cómo empeora la IR el pronóstico de la IC? En la serie que comentamos, destaca el mal pronóstico de los pacientes con IR severa, que afecta tanto al grupo con FS-P como con FS-D, aunque con mayor graveInsuficiencia combinada cardiorrenal: una clave evolutiva y terapéutica en el fallo cardíaco Carlos Carameloa y Paloma Gilb

Anemia in Heart Failure: Pathophysiology, Pathogenesis, Treatment, and Incognitae

Although anemia now occupies an important place in our present understanding of the pathogenesis of heart failure, the condition is surrounded in mystery. Anemia is highly prevalent in patients with heart failure and is of great clinical significance. However, the treatment targets for anemia in patients with heart failure have still not been accurately defined. The present article reviews of the clinical and pathophysiological characteristics of anemia in this context. Particular emphasis has been placed on cellular and molecular regulatory mechanisms, and their implications for treatment.

Combined Cardio-Renal Failure: a Key Factor in Heart Failure Progression and Therapy

Cardiovascular disease is the primary cause of morbidity/mortality in the Spanish setting, justifying the extraordinary research effort being made to determine its etiopathogenesis, to predict its prognosis, and to improve treatment. In recent years there has been growing recognition of the role of kidney failure in the overall prognosis of cardiovascular disease.1 Varying in severity, kidney failure very commonly accompanies heart failure, and recent work suggest it may predict the risk of death in congestive heart disease better than either the ejection fraction or the New York Heart Association (NYHA) classification.2 In this issue of the REVISTA ESPANOLA DE CARDIOLOGIA, Grigorian-Shamagian et al3 analyze the role of kidney failure as a predictor of heart failure mortality. Their data, although collected only in hospitalized patients, bring to light information of interest to this important topic. To begin with, this is the first Spanish study on this issue that analyzes a large number of patients (n=522). Secondly, unlike other studies in which only systolic dysfunction is taken into account, the present work examines patients with both preserved and reduced systolic function. From a clinical standpoint, the results provide useful information highlighting the importance of kidney dysfunction in the progress of heart failure. How does kidney failure worsen the prognosis of heart failure? Among the patients examined by GrigorianShamagian et al, those with severe kidney failure—a problem seen among members of the subgroups with preserved and (especially) reduced systolic function—had a poorer prognosis. It should be noted that until now there have been no studies that describe possible differences in kidney function in subgroups of this type. Large scale Combined Cardio-Renal Failure: a Key Factor in Heart Failure Progression and Therapy Carlos Carameloa and Paloma Gilb

Insuficiencia combinada cardiorrenal: una entidad clínica emergente

La enfermedad cardiovascular es la primera causa de morbimortalidad en Espana. La presencia de insuficiencia renal tiene un valor pronostico y obliga a modificar el abordaje terapeutico. Identificamos con el termino de insuficiencia combinada cardiorrenal (ICR) a una entidad diferenciada, infraestimada en nuestra poblacion, en la que coexisten el fallo renal y el cardiaco. Los pacientes con ICR son autenticos supervivientes de la aplicacion de diversas tecnologias y po-seen un equilibrio hemodinamico e hidrosalino diferente del de las insuficiencias cardiaca o renal aisladas. El diagnostico temprano de esta enfermedad, su seguimiento, tanto hospitalario como ambulatorio, asi como un manejo especifico, condicionan su pronostico. El aspecto clave del control de estos enfermos reside en el mantenimiento de un delicado balance de liquidos, que es siempre individual y personalizado. Este tipo de manejo requiere un entrenamiento y mentalizacion particulares del personal sanitario, con una vision integrada de los multiples factores implicados. El diseno de un plan estructurado segun objetivos, y la comprension del equilibrio de cada individuo son una pieza clave del tratamiento de la ICR. La presente revision se basa en conceptos tradicionales, actualizados de una manera practica, y trata de llamar la atencion sobre una entidad clinica en acelerado crecimiento.

Cardio-renal insufficiency: the search for management strategies

PURPOSE OF REVIEW This review focuses on the pathophysiology and treatment of an increasingly common entity, cardio-renal insufficiency. Cardio-renal insufficiency is more than a simultaneous cardiac and renal disease. Patients with this condition live within a fragile equilibrium challenged by the interaction of profibrogenic, atherosclerotic, neurohumoral, and other less known factors. Regarding therapy, the avoidance of oscillations between overfilled-decompensated and emptied-overtreated states becomes of critical importance. Particular focus should be paid to personalized treatment, adjusted according to heart and kidney reserve, the predictable complications of therapy, prevention of decompensations, simple measures-based follow-up and alternative procedures. RECENT FINDINGS Recent studies have established the important repercussions of unbalanced renal function on cardiovascular prognosis. In the heart failure setting, trials involving extensive cohorts of ageing or comorbidity-affected patients are presently under way. Special attention should be paid to recognize the presence of renal failure coexisting with heart failure, especially in patients with deceivingly near-normal plasma creatinine. Formulae to predict creatinine clearance are being increasingly incorporated into daily clinical practice. Disturbed renal function is an underappreciated prognostic factor in heart failure, and renal failure is frequently viewed as a relative contraindication to some proven efficacious therapies. SUMMARY Cardio-renal insufficiency is an emerging entity, with affected individuals surviving with extreme degrees of simultaneous heart failure and renal failure. Management of the condition is an intellectually demanding process. Crucial to this management is extensive medical expertise and an in-depth understanding of the particular renal, haemodynamic and internal milieu equilibrium of the patients.