Proteinuria-Lowering Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Chronic Kidney Disease Patients: A Real-World Multicentric Study.

Control of dyslipidemia in chronic kidney disease (CKD) is not always guaranteed with statins and/or ezetimibe. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have opened up a new era in lipid control, but their effect on renal function and proteinuria in real life have not yet been evaluated. The aim of the present study was to analyze the evolution of renal function and proteinuria in a cohort of CKD patients treated with PCSK9i. This retrospective multicentric cohort study included CKD patients treated with PCSK9i. Baseline epidemiological data, comorbidities and laboratory findings (including estimated glomerular filtration rate [eGFR], proteinuria and lipid profile) were collected. The evolution of renal function, proteinuria and lipid profile was analyzed during the 1-year follow-up. The cohort included 76 patients (68% male, mean age 66 ± 10 years). The mean baseline creatinine was 1.55 ± 0.77 mg/dL, and the mean eGFR was 52 ± 22 mL/min/1.73 m2. Reductions in LDL-cholesterol, total cholesterol and triglycerides during the first month were 51 ± 25%, 32 ± 25% and 11 ± 40%, respectively, levels that remained stable throughout the first year (p < 0.001 for LDL-cholesterol and total cholesterol trends and p = 0.002 for triglyceride trend). During follow-up, proteinuria improved from 57 (9-481) to 30 (7-520) mg/g (p = 0.021). In addition, eGFR remained stable, and no adverse events were reported. In our cohort, dyslipidemia treatment with PCSK9i was associated with decreased proteinuria in CKD patients, an effect that might be due to reduced lipid nephrotoxicity. Clinical trials are needed to further investigate whether this impact on proteinuria can significantly slow CKD progression in the long term.

Effectiveness of biosimilar drugs in the treatment of renal anemia: A case series. / Efectividad del uso de biosimilares en el tratamiento de la anemia en pacientes con enfermedad renal crónica: serie de casos.

INTRODUCTION: Patients with chronic kidney disease usually have anemia secondary to an erythropoietin deficit. The emergence of biosimilar drugs of erythro-poiesis-stimulating agents ensures broader access to these treatments. OBJECTIVE: This study analyzes the effectiveness of an epoetin α biosimilar drug in chronic kidney disease patients with anemia. METHODS: This observational retrospective study enrolled 111 consecutive outpatients with chronic kidney disease and anemia and criteria for using eryth-ropoietin-stimulating agents. We collected baseline epidemiological and comorbidity data, as well as hematological and renal function infor-mation. We analyzed the effectiveness of the biosimilar agent in naïve patients and those who already had other erythropoiesis-stimulating agents. RESULTS: The 111 included patients had a mean age of 83 ± 8 years, and 54% were males. We found that patients who previously received erythropoiesis-stimulating agents, maintained hemoglobin values at two months of treatment with the biosimilar, while the naïve group significantly raised their hemoglobin values (P < 0.001). Renal function remained stable within the whole sample. The cost of using erythropoiesis-stimulating agents was reduced by a mean of 82 ± 17% with the biosimilar drug. CONCLUSION: Using a biosimilar of epoetin α is effective in patients with chronic kidney disease and anemia and significantly reduces costs.

INTRODUCCIÓN: Los pacientes con enfermedad renal crónica presentan anemia que, en gran parte, se debe a un defecto en la producción de eritropoyetina. La aparición de fármacos biosimilares de agentes estimulantes de la eritropoyesis garantiza un acceso más generalizado a dichos fármacos. OBJETIVO: Los pacientes con enfermedad renal crónica presentan anemia que, en gran parte, se debe a un defecto en la producción de eritropoyetina. MÉTODO: Se trata de un estudio observacional retrospectivo, en el que analizamos datos de 111 pacientes consecutivos de las consultas de nefrología con enfermedad renal crónica, anemia y con criterios de uso de agentes estimulantes de la eritropoyesis. Recogimos datos basales epidemiológicos y de comorbilidad, así como hematológicos y de función renal. Analizamos la efectividad del fármaco en aquellos pacientes naïve así como en aquellos que ya tenían otros agentes estimulantes de la eritropoyesis, y que habían iniciado tratamiento con el biosimilar. RESULTADOS: De los 111 pacientes incluidos, el 54% eran varones y la edad media se situó en 83 ± 8 años. En los pacientes que ya estaban en tratamiento con agentes estimulantes de la eritropoyesis, el uso del biosimilar mantuvo los valores de hemoglobina a los dos meses de tratamiento, mientras que en el grupo naïve se produjo un ascenso significativo de los mismos (p < 0,001). No hubo cambios en la función renal en ninguno de los grupos. El costo del uso de agentes estimulantes de la eritropoyesis se redujo una media de 82 ± 17% con el uso del biosimilar. CONCLUSIONES: El uso de un biosimilar de epoetina αα es efectivo en pacientes con enfermedad renal crónica y genera una importante reducción de costos.

Efectividad y seguridad del uso de inhibidores de PCSK9 en el tratamiento de la dislipidemia en el paciente con insuficiencia renal / Efficacy and safety of the PCSK9 inhibitors in the treatment of dyslipidemia in chronic kidney disease

El uso de fármacos inhibidores de la proprotein convertase subtilisin/kexin type 9 (iPCSK9) ha supuesto un cambio en el tratamiento de la dislipidemia en sus efectos sobre los eventos cardiovasculares. Actualmente, disponemos de 2principios activos comercializados (evolocumab y alirocumab) que tienen indicación en los pacientes que no alcanzan unos valores de lipoproteína de baja densidad (LDL) inferior a 100mg/dl habiendo presentado un evento cardiovascular previo y con dosis máximas o intolerancia a las estatinas. Los ensayos clínicos con iPCSK9 han incluido a pacientes con enfermedad renal, aunque con límites en el filtrado glomerular de hasta 20ml/min/1,73 m2 en el menos restrictivo de ellos. Los subanálisis de estos ensayos clínicos han demostrado eficacia en los pacientes con insuficiencia renal, tanto en la mejoría del perfil lipídico como en la reducción de eventos cardiovasculares. Derivado de su intenso efecto en la reducción de colesterol LDL han surgido algunas dudas sobre su seguridad que actualmente están resueltas y que confieren a los iPCSK9 un evidente beneficio cardiovascular también pacientes con enfermedad renal

The use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has changed the clinical practice of dyslipidemia and their effects in cardiovascular events. Nowadays 2active principles have been commercialized (evolocumab and alircumab) with indication in patients with low-density lipoprotein (LDL) cholesterol over 100mg/dl, history of cardiovascular events and higher statins doses prescribed. Clinical trials with PCSK9i have included chronic kidney disease (CKD) patients, although glomerular filtration rate has been limited up to 20ml/min/1,73m2 or higher. The published sub-analysis of them have demonstrated at least the same efficacy (in reduction of LDL and cardiovascular events) and safety in patients with CKD. However, as these drugs are very powerful in reducing LDL cholesterol, some safety concerns appeared in the past. Once safety is probed, we conclude that PCSK9i are beneficial for CKD patients

Efficacy and safety of the PCSK9 inhibitors in the treatment of dyslipidemia in chronic kidney disease. / Efectividad y seguridad del uso de inhibidores de PCSK9 en el tratamiento de la dislipidemia en el paciente con insuficiencia renal.

The use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has changed the clinical practice of dyslipidemia and their effects in cardiovascular events. Nowadays 2active principles have been commercialized (evolocumab and alircumab) with indication in patients with low-density lipoprotein (LDL) cholesterol over 100mg/dl, history of cardiovascular events and higher statins doses prescribed. Clinical trials with PCSK9i have included chronic kidney disease (CKD) patients, although glomerular filtration rate has been limited up to 20ml/min/1,73m2 or higher. The published sub-analysis of them have demonstrated at least the same efficacy (in reduction of LDL and cardiovascular events) and safety in patients with CKD. However, as these drugs are very powerful in reducing LDL cholesterol, some safety concerns appeared in the past. Once safety is probed, we conclude that PCSK9i are beneficial for CKD patients.

Experiencia clínica con sacubitrilo/valsartán en pacientes con insuficiencia renal: la visión del nefrólogo / Sacubitril/valsartan in chronic kidney disease, the nephrologist point of view

ANTECEDENTES Y OBJETIVO: Sacubitrilo/valsartán ha demostrado ser eficaz en la reducción de la morbimortalidad cardiovascular en los pacientes con disfunción sistólica. El objetivo del presente estudio fue analizar la evolución de pacientes con enfermedad renal crónica (ERC) tras el inicio de sacubitril/valsartán. MATERIAL Y MÉTODOS: Se incluyó a 66 pacientes consecutivos que acudieron a las consultas externas de Nefrología, con ERC y disfunción sistólica. Los criterios de inclusión fueron: presentar una clase funcional II a IV de la New York Heart Association (NYHA) con el tratamiento médico optimizado y ERC estadios 1 a 4. Se recogieron datos basales epidemiológicos y de comorbilidad en el momento de inicio del fármaco. En los meses 1 y 3 se tituló la dosis de sacubitril/valsartán (en función de la tolerabilidad). En cada visita se recogieron datos analíticos de función renal y biomarcadores cardiacos, entre otros. Se analizaron los datos a los 6 meses (fin del seguimiento). RESULTADOS: De los 66 pacientes, 42 eran varones (63%), con una edad media de 73 ± 15 años. La creatinina media fue de 1,42 ± 0,5 mg/dL (filtrado glomerular CKD-EPI 50 ± 19 mL/min/1,73 m2) con una fracción de eyección del ventrículo izquierdo (FEVI) media de 31 ± 9. Al final del seguimiento, la FEVI mejoró significativamente (basal 31 ± 9 vs. final 39 ± 15; p < 0,001). En cuanto a la función renal, el filtrado glomerular por CKD-EPI presentó mejoría al mes (50 ± 19 vs. 53 ± 21 mL/min/1,73 m2; p = 0,005), que se mantuvo estable (filtrado glomerular al final del seguimiento 51 ± 18mL/min/1,73 m2). Abandonaron el tratamiento 7 pacientes (10,6%). CONCLUSIÓN: En nuestra experiencia, sacubitril/valsartán es seguro en los pacientes con insuficiencia renal crónica y estabiliza la función renal a los 6 meses

BACKGROUND AND OBJECTIVES: Sacubitril/valsartan reduces cardiovascular morbidity and mortality in patients with systolic dysfunction. The aim of the present study was to assess the evolution of chronic kidney disease (CKD) patients after initiating sacubitril/valsartan. MATERIAL AND METHODS: We included 66 consecutive CKD patients with systolic dysfunction followed up in outpatient care. Patients had to meet the inclusion criteria of having a New York Heart Association class II to iv, receiving maximum tolerated doses of optimal medical therapy and CKD stages 1 to 4. At baseline, comorbidities and epidemiological data were collected and low doses of sacubitril/valsartan were initiated. At month 1 and 3, doses of sacubitril/valsartan were increased up to the maximum doses if tolerated. In each visit, renal function and cardiac biomarkers were recorded. All the data were analyzed at the end of follow up (6 months). RESULTS: Of the 66 patients, 42 (63%) were men, with a mean age of 73 ± 15 years. Mean creatinine at baseline was 1.42 ± 0.5 mg/dL (glomerular filtration rate estimated by CKD-EPI was 50 ± 19 mL/min/1.73 m2) and mean left ventricular ejection fraction (LVEF) was 31 ± 9%. At the end of follow up, LVEF improved from 31 ± 9% to 39 ± 15% (P < 0.001). After one month of treatment, renal function improved up to 53 ± 21 mL/min/1.73 m2, P = 0.005. For the remaining follow-up time, glomerular filtration rate remained stable (mean at end of follow-up 51±18 mL/min/1.73 m2). Seven patients (10.6%) withdrew from treatment. CONCLUSION: In our experience, sacubitril/valsartan is safe in CKD, offering stability in CKD progression after 6 months

Sacubitril/valsartan in chronic kidney disease, the nephrologist point of view. / Experiencia clínica con sacubitrilo/valsartán en pacientes con insuficiencia renal: la visión del nefrólogo.

BACKGROUND AND OBJECTIVES: Sacubitril/valsartan reduces cardiovascular morbidity and mortality in patients with systolic dysfunction. The aim of the present study was to assess the evolution of chronic kidney disease (CKD) patients after initiating sacubitril/valsartan. MATERIAL AND METHODS: We included 66 consecutive CKD patients with systolic dysfunction followed up in outpatient care. Patients had to meet the inclusion criteria of having a New York Heart Association class ii to iv, receiving maximum tolerated doses of optimal medical therapy and CKD stages 1 to 4. At baseline, comorbidities and epidemiological data were collected and low doses of sacubitril/valsartan were initiated. At month 1 and 3, doses of sacubitril/valsartan were increased up to the maximum doses if tolerated. In each visit, renal function and cardiac biomarkers were recorded. All the data were analyzed at the end of follow up (6 months). RESULTS: Of the 66 patients, 42 (63%) were men, with a mean age of 73±15 years. Mean creatinine at baseline was 1.42±0.5 mg/dL (glomerular filtration rate estimated by CKD-EPI was 50±19 mL/min/1.73 m2) and mean left ventricular ejection fraction (LVEF) was 31±9%. At the end of follow up, LVEF improved from 31±9% to 39±15% (P <0.001). After one month of treatment, renal function improved up to 53±21 mL/min/1.73 m2, P=0.005. For the remaining follow-up time, glomerular filtration rate remained stable (mean at end of follow-up 51±18 mL/min/1.73 m2). Seven patients (10.6%) withdrew from treatment. CONCLUSION: In our experience, sacubitril/valsartan is safe in CKD, offering stability in CKD progression after 6 months.