Molecular mechanisms of nephrotoxicity and new experimental therapies in renal disease
Pathophysiology and Therapy of Immune and Inflammatory Diseases
Hospital Universitario Fundación Jiménez Díaz
DESCRIPTION OF THE OFFER
Acute kidney injury (AKI) is a sociosanitary and economic problem. Mortality is as high as 50%, and even a short-timed injury contributes to a persistently higher mortality. Moreover, 20% of patients with AKI develop chronic kidney disease (CKD) and end stage renal disease (ESRD). Inflammation, parenchymal cell loss, and nephron loss are features of AKI that may eventually lead to tubulointerstitial fibrosis. Currently, no satisfactory treatment attenuates AKI or accelerates recovery. Hence, development of biological or pharmacological therapies against AKI is a pending matter subjected to drug discovery.
Chemokines are important soluble mediators of kidney inflammation which are produced in delimited areas of damaged and inflamed tissues. Chemokines attract specific leukocytes subsets to the inflammatory focus and have an active role regulating innate as well as adaptive immune responses during AKI. Thus, chemokines arise as potential molecular targets in AKI.
As part of an active project, we are blocking a CCL-family chemokine in order to establish its role during the acute and progressive kidney injury as well as its potential utility as pharmacological target. Moreover, we investigate the chemokine behavior as diagnostic/prognostic biomarker in the same experimental setting.
In a second active project with a common objective focused on nephroprotection during AKI, we are currently investigating the utility of new experimental drugs (nanomedicines) to treat AKI.
The laboratory strategy encompasses the use of cellular and mice AKI models, the latter developed on wild-type and specific KO genotypes. Biochemical techniques to analyze gene and protein expression and immunohistochemical detection of molecular targets or signaling pathways are commonly used. Other methodologies currently used are confocal microscopy and flow cytometry.
Biomolecules & Cell D.
ADRIÁN M. RAMOS