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)

Mesenchymal stem cell therapy in acute kidney injury (AKI): review and perspectives

SUMMARY INTRODUCTION: Acute kidney injury (AKI) is highly prevalent today. It has a multifactorial aetiology and affects people of all ages, genders and ethnicities. Its treatment is essentially supportive of renal function substitution, so new treatment alternatives such as mesenchymal stem cell therapy (MSCs) should be investigated. METHODS: This review encompasses our understanding of the main mechanisms of action of MSCs in preclinical models of AKI by renal pedicle clamping ischemia-reperfusion, chemotherapy (cisplatin) and kidney transplantation in small and large animals, as well as outcomes in patients with AKI due to ischemia and kidney transplantation. RESULTS: Cellular therapy with MSCs has benefits in preclinical studies of AKI through various mechanisms, such as anti-inflammatory, antiapoptotic, oxidative anti-stress, antifibrotic, immunomodulatory and proangiogenic. In humans, MSC therapy is safe and effective. However, the challenges of MSC cell therapy include investigating protocols about the optimal dose of these cells, the route and frequency of appropriate administration, and the design of further biodistribution studies over a long follow-up period. In addition, a better understanding of molecular signalling and cellular interactions in the microenvironment of each organ and tissue is needed in order to define the best time to administer MSCs. Another challenge would be to mitigate the heterogeneity of the profile of cultured MSCs through preconditioning approaches. CONCLUSIONS: Cellular therapy with MSCs is very promising and should be part of the treatment of AKI patients in combination with other approaches already available, helping to accelerate recovery and/or slow the progression to chronic kidney disease. Randomized, multicentre controlled studies are needed to develop robust protocols that validate population-based cell therapy with MSCs.