Aportes de la biotecnología al diagnóstico y tratamiento de la enfermedad renal crónica y comorbilidades frecuentes / Biotechnology contribution to the diagnosis and treatment of chronic kidney disease and frequent comorbidities

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)

Laboratory evidence for the hematopoietic potential of Beta vulgaris leaf and stalk extract in a phenylhydrazine model of anemia

This study was designed to provide laboratory evidence supporting the hematopoietic effect of Beta vulgaris (beet) leaf aqueous extract in phenylhydrazine-induced anemia model in albino rats. Extraction of the leaves/stalks was done by maceration in 30% hydro-ethanol for 48 h. An intraperitoneal injection of 20 mg/kg phenylhydrazine was applied for two consecutive days to develop hemolytic anemia on the 4th day after the 1st injection in 24 of 30 male albino rats. The animals were divided into 5 groups and received the following treatments: standard (ferrous ascorbate + folic acid; 13.5 + 0.135 mg/kg), B. vulgaris extract (100 and 200 mg/kg), or left untreated (normal and diseased controls). Blood samples were taken at 0, 4, 8, and 12 days of the experiment for hematological and clinico-chemical analysis. Beet leaf extract significantly restored the levels of red blood cells, white blood cells, hemoglobin, and hematocrit in dose- and time-dependent manners. Blood indices have been significantly corrected. Erythropoietin level was maintained at higher levels. Erythrocytic membrane oxidation biomarker (malondialdehyde) level was significantly reduced compared to the anemic untreated group. The extract exhibited potent, concentration (4-512 μg/mL)-dependent antioxidant activity indicated by the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay, with IC50 value of 37.91 μg/mL. Beet leaf extract resulted in detection of flavonoid and phenolic compounds that may underlie its hematinic properties. These findings may indicate B. vulgaris as a good natural source for pharmaceutical preparations with hematopoietic effects and treatment of anemia and/or associated conditions.

12-week clinical effects of erythropoietin espogen in end stage renal patients undergoing hemodialysis.

BACKGROUND: Anemia is one of most common complications in end stage renal disease (ESRD) patients. Erythropoietin has been recommended for treatment of anemia in these patients. OBJECTIVES: To evaluate the clinical efficacy, safety and usefulness of newly imported erythropoietin, called Espogen, usage in ESRD undergoing hemodialysis. MATERIAL AND METHOD: An open, non-comparative, prospective study of administered Espogen was conducted in 30 ESRD patients undergoing hemodialysis for a 12 week period. Eligible criteria included hemoglobin of less than 8 g%, hematocrit of less than 25% for at least three consecutive months with a serum ferritin of more than 100 ng%. Initial dose of drug was 150 units/kg/week subcutaneously, two or three times a week and dosage was adjusted to maintain the Hb at 10-12g%. RESULTS: In 28 patients, hemoglobin and hematocrit were increased significantly from 7.1 +/- 1.14 g/dl and 22.1 +/- 3.24% at baseline to 10.1 +/- 1.49 g/dl and 31.7 +/- 4.01% at the end of the study period respectively (p < 0.05). Mean weekly of Espogen dosage was 8390 +/- 2452.7 IU/week, which was 152.1 IU/kg/week. Some patients could reduce the dose at week 10. Reticulocyte increased significantly from 0.69 +/- 0.58% at baseline to highest value, 1.41 +/- 0.74 at 2 week and 1.30 +/- 0.66 at the end of the present study. Serum vitamin B12, serum folate, and red blood cell folate were not significantly changed. However serum ferritin decreased significantly from 840.6 +/- 948.95 to 582.7 +/- 990.70 ng/ml (p < 0.05). General condition including SF-36 score and tiredness were improved. There were no significant adverse events except mean arterial blood pressure of pre dialysis value which was statistically significant increased at the end of the present study (from 101.0 +/- 17.65 at week 0 and 110.4 +/- 16.8 mmHg at week 12, p = 0.0223). CONCLUSION: This clinical study showed that Espogen has proven effective and safe for treatment of anemia in hemodialysis patients. No serious adverse events occurred during the study period.

The evolution of purinergic receptors involved in recognition of a blood meal by hematophagous insects

Many blood feeders use adenine nucleotides as cues for locating blood meal. Structure-activity relationship of adenine nucleotides as phagostimulants varies between closely-related species of blood feeders. It is suggested that a preexisting diverse pool of nucleotide-binding proteins present in all living cells, serves as a source of receptor proteins for the gustatory receptors involved in blood detection. It is proposed that the selection of any such nucleotide-binding protein is random.