ABSTRACT
Este trabajo tiene como objetivo revisar las contribuciones de la biotecnología, en relación con el tratamiento, diagnóstico y la monitorización de la enfermedad renal crónica (ERC) y sus comorbilidades más frecuentes, especialmente la anemia. En relación con los tratamientos, enfocamos el desarrollo de productos biofarmacéuticos como los agentes estimulantes de la eritropoyesis (ESA), que fueron los primeros biofármacos utilizados para el tratamiento de la anemia asociada a la ERC; analizamos sus características y utilización actual después de varios años de experiencia clínica, así como también otras alternativas en desarrollo. Revisamos distintos tipos de bioterapias, la utilización de las células estromales mesenquimales de médula ósea (MSC) y tratamientos alternativos con modificaciones dietarias, que se basan en la asociación entre la microbiota intestinal de los pacientes renales crónicos y sus condiciones fisiopatológicas. Finalmente, en relación con el diagnóstico y monitorización, nos referimos al estudio y validación de biomarcadores diagnósticos, predictivos y terapéuticos que han permitido optimizar los resultados clínicos en este tipo de pacientes. (AU)
The aim of this work is to review the contributions of biotechnology, in relation to the treatment, diagnosis and monitoring of chronic kidney disease (CKD) and its most frequent comorbidities, especially anemia. Regarding the treatment, we focus on the development of biopharmaceutical products such as erythropoiesis stimulating agents (ESA), which were the first biopharmaceuticals used to treat anemia associated with chronic kidney disease (CKD). We analyzed their characteristics and their current use after several years of clinical experience, as well as other alternatives in development. We also review different types of biotherapies, the use of bone marrow mesenchymal stromal cells (MSC) and alternative treatments with dietary modifications, which are based on the association between the intestinal microbiota of chronic kidney patients and their pathophysiological conditions. Finally, in relation to diagnosis and monitoring, we refer to the study and validation of diagnostic, predictive and therapeutic biomarkers that have made clinical results possible to be optimized in this type of patient. (AU)
Subject(s)
Humans , Biological Therapy/trends , Renal Insufficiency, Chronic/therapy , Quality of Life , Biotechnology , Biomarkers , Erythropoietin/deficiency , Probiotics/therapeutic use , Mesenchymal Stem Cell Transplantation/trends , Erythropoiesis/drug effects , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/diet therapy , Renal Insufficiency, Chronic/rehabilitation , Prebiotics/classification , Glycoside Hydrolase Inhibitors/therapeutic use , Gastrointestinal Microbiome , Hematinics/administration & dosage , Hematinics/pharmacology , Hematinics/pharmacokinetics , Anemia/diagnosis , Anemia/etiology , Anemia/drug therapyABSTRACT
BACKGROUND: It is known that one of the leading causes of morbidity in chronic kidney disease (CKD) is the anemic syndrome. Although the pathogenic mechanisms of anemia are multiple, erythropoietin deficiency appears as the dominant factor. Patients in hemodialysis (HD) have a high prevalence of protein energy wasting (PEW) that may explains the poor response to Erythropoietin (EPO). METHODS: Retrospective cohort study of patients on HD from January to December 2014. The participants were classified according to a diagnostic of PEW using the "Malnutrition Inflammation Score" (MIS) and bioimpedance analysis (BIA) measurement of body composition at the start of erythropoietin therapy and after 3 months of follow up. We performed descriptive statistics and analyzed the differences between groups with and without PEW considering their responsiveness. In addition, we calculated the relative risk of EPO resistance, considering p value < 0.05 as statistically significant. RESULTS: Sixty-one patients ended the follow up. Both groups were similar in basal hemoglobin, hematocrit and other hematopoiesis markers (p = NS). Patients without PEW have a decrease risk for poor response to treatment with EPO (RR = 0.562 [95% CI, 0.329-0.961-]) than those with PEW. Finally, hemoglobin concentrations were evaluated at baseline and every four weeks until week 12, finding a statistically significant improvement only in patients without PEW according MIS (p < 0.05). CONCLUSIONS: PEW is an incremental predictor of poor responsiveness to EPO in HD patients, thus, it is important to consider correcting malnutrition or wasting for a favorable response to treatment with EPO.
Subject(s)
Anemia/drug therapy , Erythropoietin/therapeutic use , Hematinics/therapeutic use , Kidney Failure, Chronic/therapy , Protein-Energy Malnutrition/blood , Renal Dialysis/adverse effects , Adult , Aged , Anemia/blood , Anemia/etiology , Body Composition , Creatinine/blood , Drug Resistance , Electric Impedance , Erythropoietin/administration & dosage , Erythropoietin/deficiency , Female , Follow-Up Studies , Glomerular Filtration Rate , Hematinics/administration & dosage , Hematocrit , Hemoglobin A/analysis , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Male , Middle Aged , Nutritional Status , Probability , Protein-Energy Malnutrition/diagnosis , Protein-Energy Malnutrition/etiology , Retrospective Studies , Risk , Sex Factors , Statistics, Nonparametric , Time Factors , Young AdultABSTRACT
Anemia is an inevitable complication of hemodialysis, and the primary cause is erythropoietin deficiency. After diagnosis, treatment begins with an erythropoiesis-stimulating agent (ESA). However, some patients remain anemic even after receiving this medication. This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016. Clinical data was collected, and the response to αEPO treatment was evaluated using the erythropoietin resistance index (ERI). The ERI was defined as the weekly weight-adjusted αEPO dose (U/kg per week)/hemoglobin level (g/dL). A longitudinal linear regression model was fitted with random effects to verify the relationships between clinical and laboratory data and ERI. We enrolled 99 patients (average age, 45.7 (±17.6) years; male, 51.5%; 86.8% with hypertension). The ERI showed a significant positive association with serum ferritin and C-reactive protein, percentage interdialytic weight gain, and continuous usage of angiotensin receptor blocker (ARB) hypertension medication. The ERI was negatively associated with serum iron and albumin, age, urea reduction ratio, and body mass index. Our findings indicate that resistance to αEPO was related to a low serum iron reserve, an inflammatory state, poor nutritional status, and continuous usage of ARBs.
Subject(s)
Anemia/drug therapy , Anemia/etiology , Drug Resistance/drug effects , Epoetin Alfa/therapeutic use , Hematinics/therapeutic use , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic/therapy , Adult , Body Mass Index , Erythropoiesis/drug effects , Erythropoietin/deficiency , Female , Hemoglobins/analysis , Humans , Iron/blood , Linear Models , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Reference Values , Renal Insufficiency, Chronic/complications , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Anemia is an inevitable complication of hemodialysis, and the primary cause is erythropoietin deficiency. After diagnosis, treatment begins with an erythropoiesis-stimulating agent (ESA). However, some patients remain anemic even after receiving this medication. This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016. Clinical data was collected, and the response to αEPO treatment was evaluated using the erythropoietin resistance index (ERI). The ERI was defined as the weekly weight-adjusted αEPO dose (U/kg per week)/hemoglobin level (g/dL). A longitudinal linear regression model was fitted with random effects to verify the relationships between clinical and laboratory data and ERI. We enrolled 99 patients (average age, 45.7 (±17.6) years; male, 51.5%; 86.8% with hypertension). The ERI showed a significant positive association with serum ferritin and C-reactive protein, percentage interdialytic weight gain, and continuous usage of angiotensin receptor blocker (ARB) hypertension medication. The ERI was negatively associated with serum iron and albumin, age, urea reduction ratio, and body mass index. Our findings indicate that resistance to αEPO was related to a low serum iron reserve, an inflammatory state, poor nutritional status, and continuous usage of ARBs.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Anemia/drug therapy , Anemia/etiology , Drug Resistance/drug effects , Epoetin Alfa/therapeutic use , Hematinics/therapeutic use , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic/therapy , Body Mass Index , Erythropoiesis/drug effects , Erythropoietin/deficiency , Hemoglobins/analysis , Iron/blood , Linear Models , Longitudinal Studies , Prospective Studies , Reference Values , Renal Insufficiency, Chronic/complications , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
La eritropoyetina u hormona estimulante de la eritropoyesis, de origen renal, a pesar de haber sido identificada a finales de los años 50, sólo ha podido ser usada clínicamente en años recientes, cuando se logró su producción en masa mediante técnicas de ingenieria genética. Hoy se dispone de dos tipos de Eritropoyectina recombinante humana (RHuEpo):Ó y ß. En esta guía se enumeran las indicaciones, especialmente en pacientes con anemia atribuible a hemodiálisis crónica, y en otras condiciones; y se hace un listado de las contraindicaciones, detallando después los criterios para la inclusión de los pacientes en ese protocolo.
Subject(s)
Humans , Erythropoietin/administration & dosage , Erythropoietin/deficiency , Erythropoietin/adverse effects , Erythropoietin/therapeutic use , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/pathologyABSTRACT
Se analizan en forma prospectiva las alteraciones hematológicas en 20 pacientes con Leishmaniais mucocutánea (refractarios al tratamiento con antímoniales pentavalentes) que recibieron tratamiento con anfotericina B. El medicamento se administró en dosis de 50mg endovenosos hasta completar 1500 mg de dosis total acumulado (150 mg por semana). El 95 por ciento de pacientes presentó algún tipo de complicación hematológica, siendo las más frecuentes anemía (95 por ciento) y retículocitopenia (90 por ciento). La anemia fue de tipo normocíticanormocrómica con pobre respuesta medular, intensidad leve en la mayoría, y reversible. La disminución del hematocrito fue temprana y con una dosis acumulada relativamente pequeña (250 - 550 mg), luego de la cual el hematocrito se estabilizó. Se encontró correlación entre la caída del hematocrito y la dosis acumulada. El principal mecanismo para el desarrollo de la anemia seria una disminución de la producción de los globulos rojos por supresión de la médula ósea como consecuencia de un bloqueo en la producción de eritropoyetina, más un efecto tóxico directo sobre la médula ósea. Las alteraciones en el número de eosinófilos son difíciles de interpretar, pues al parecer tanto la enfermedad de fondo como la anfotericina B causarían alteraciones en esta línea celular. Se encontró leucopenia y linfopenia en 5 por ciento de pacientes, estos hallazgos se relacionaron a la presencia de citofagocitosis medular. No se encontró ningún caso de trombocítopenia, pero si una disminución significativa temprana del número de plaquetas, probablemente asociado a depresión medular de la serie megacariocítica