The acute phase response is traditionally characterized by hepatic synthesis of proteins as an inflammatory response to injury, with interleukin 6 (IL6) being the key mediator. In contrast, microarray studies in human renal transplant implantation biopsies, indicate a strong acute phase response in the deceased donor kidney, associated with a significant upregulation of oncostatin M receptor (OSMR) The aim of this study was to determine whether the kidney can generate a strong acute phase response, mediated by the OSM/OSMR gateway. Genes associated with the IL6 cytokine family and acute phase reactants were analyzed by real-time RT-PCR in 4 groups of human biopsies spanning a spectrum of renal injury. OSM, OSMR and fibrinogen (FGB) were progressively more highly expressed from pre-nephrectomy, living donor, deceased donor to discarded deceased donor kidneys, suggesting correlation with severity of injury and local renal synthesis. Acute phase response gene expression was analyzed in human proximal tubular cells in culture in response to OSM. OSM induced a significant increase in expression of FGB, OSMR, serpin peptidase inhibitor A1, IL6 and lipopolysaccharide binding protein, and a decrease in IL6R. These changes were largely attenuated by co-incubation with an OSMR blocking antibody, indicating the OSM effect was mediated through OSMR. OSM also resulted in a significantly altered expression of acute phase genes compared to IL6 or leukemia inhibitory factor, suggesting that OSM is the predominant cytokine mediating the renal tubular acute phase response. In conclusion, the renal parenchyma is capable of generating a strong acute phase response, likely mediated via OSM/OSMR.