Targeting chemokines in proteinuria-induced renal disease.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
Department of Nephrology, IIS-Fundación Jiménez Díaz, Autonoma University, Avda. Reyes Católicos 2, 28040 Madrid, Spain. jamoreno@fjd.es
Juan Antonio
JA
Moreno
Sara
S
Moreno
Alfonso
A
Rubio-Navarro
Cristina
C
Sastre
Luis Miguel
LM
Blanco-Colio
Carmen
C
Gómez-Guerrero
Alberto
A
Ortiz
Jesús
J
Egido
D000818:Animals; D018925:Chemokines / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D011507:Proteinuria / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism
D018925:Chemokines; D019707:Receptors, Chemokine