Among the genes identified in our laboratory that are kidney-specific and regulated by androgens at the transcriptional level we are particularly focused on the one that codes for the kidney androgen-regulated protein (KAP). Besides characterization of  the functional promoter elements that enable KAP expression in proximal tubule epithelial cells, we have generated a transgenic (Tg) mouse model that overexpresses KAP in proximal tubule cells under the presence of androgens, in order to mimick the endogenous KAP expression pattern. KAP Tg mice show altered lipid metabolism, glycosuria, proteinuria and hypertension, as well as focal segmental glomerulosclerosis mediated by increased oxidative stress. We are currently working in this Tg model and also preparing conditional knock-out mice to further caharacterize the role of KAP in renal pathophysiology. Moreover, we are also studying the role of KAP in the metabolic syndrome. Besides KAP, we are studying the role of KAP-interacting immunophilins  in inflammation and kidney fibrosis.

Our group is focused in research in primary or inherited tubular renal diseases, such as Dent’s Disease, Bartter syndrome, Tubular Acidosis, Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis, among others. Currently we are collaborating  with other groups in Spain, within a research project named Renaltube the main purpose of which is to build a database while facilitating access to genotyping in order to improve the clinical and molecular knowledge of primary tubulopathies. Renaltube has a web-based approach with multilateral collaboration scheme that enhances the recruitment of data and promotes the understanding of underlying mechanisms of rare inherited diseases, defines more accurate diagnostic and follow-up criteria, develops new molecular techniques and will improve the overall care of the patients. Currently we are offering the analysis of 22 genes corresponding to 23 primary tubulopathies. After two years of activity Renaltube has collected data from 222 patients, the mayority from Spain and Latin America (85.3%). The most common tubulopathies are distal renal tubular acidosis (22.5%), and classical Bartter syndrome (19.3%) followed by familial hypomagesemia with hipercalciuria and nephrocalcinosis (15.7%), and Gitelman syndrome (15%).

Overexpression of this protein in 60% of the ccRCCs has already been described. HAVR/KIM-1 overexpression in human ccRCC cell lines blocks cell differentiation and promotes cell scattering. We aim to determine the role of HAVR/KIM-1 in the development and progression of ccRCC, and its possible value as a diagnostic and prognostic biomarker. We also focus on KIM-1’s role in ischemia/reperfusion- or nephrotoxic-induced renal tubular injury. Overexpression of this protein in kidney injury has been described. However, whether its involvement is associated with processes enabling to recover tubular epithelium or potentially increasing damage is not known to this date. With the assistance of cultured renal tubular cell models, we are now investigating whether KIM-1 expression shifts are correlated with renal proximal tubule regeneration ability and, as a consequence, investigating its potential therapeutic application.