Targeting chemokines in proteinuria-induced renal disease

Abstract

Introduction: Proteinuria is a common finding in glomerular diseases that contributes to the progression of chronic kidney injury. Tubular cells reabsorb the excess of albumin and other plasma proteins from the tubular lumen, triggering several pathophysiologic responses, such as overexpression of fibrogenic mediators and inflammatory chemokines. Chemokines are implicated both in the recruitment of inflammatory infiltrate and in a number of physiological and pathological processes related to protein overload.

Areas covered: In recent years, the specific chemokines and their receptors and the intracellular signaling pathways involved in proteinuria-induced renal damage have been identified. This review provides an overview of the role of chemokines and their receptors in proteinuria-related renal disease and summarizes novel therapeutic approaches to restrain the progression of renal damage.

Expert opinion: Inhibition of chemokine-induced biological activities is a promising therapeutic strategy in proteinuric disorders. Neutralizing antibodies and small organic molecules targeting chemokines and chemokine receptors have been proven to prevent inflammation and renal damage in experimental models of protein overload. Some of these compounds are currently being tested in human clinical trials.

Keywords::

• chemokines
• inflammation
• proteinuria
• renal diseases

Acknowledgments

Grant support: FIS (Programa Miguel Servet) to JAM and Programa Estabilización Investigadores to LMB-C. Fundación Conchita Rábago to CS. Ministry of Science (SAF2009/11794) to CGG. ISCIII and FEDER funds CP04/00060, PS09/00447, Sociedad Española de Nefrologia, ISCIII-RETIC REDinREN/RD06/0016, Comunidad de Madrid/FRACM/S-BIO0283/2006, Programa Intensificación Actividad Investigadora (ISCIII/) to AO, PI10/00234 to LMB-C and ISCIII-Redes RECAVA (RD06/0014/0035), European Network (HEALTH F2-2008-200647), Euro Salud EUS2005-03565, cvREMOD, Fundacion Lilly, FRIAT and ISCIII fund PI10/00072 to JE. JA Moreno and S Moreno contributed equally to this work.

Notes

This box summarizes key points contained in the article.