Circulating levels of osteopontin are closely related to glomerular filtration rate and cardiovascular risk markers in patients with chronic kidney disease

Abstract

The pleiotropic cytokine osteopontin (OPN) is thought to be involved in the pathogenesis of atherosclerosis. However, the relationship between OPN and renal function, a cardiovascular risk factor itself, is not known. Therefore, we assessed the relationship between OPN plasma levels and renal function in patients at different stages of chronic kidney disease (CKD). We studied 49 non-diabetic and non-smoking patients with primary kidney disease at different CKD stages (K/DOQI 1-5). True glomerular filtration rate (GFR) in patients was assessed using the inulin-clearance technique. To examine the role of an abrupt change in GFR on circulating OPN, 15 living related kidney donors were studied before and after unilateral nephrectomy. Twenty matched non-smoking healthy subjects served as controls. OPN plasma levels in patients with CKD stage 1 (i.e. GFR above 90 mL min(-1) 1.73 m(-2)) were comparable with controls. OPN levels increase in a linear fashion with declining GFR (r = -0.9, P < 0.0001), so that the increase in OPN mirrors the severity of renal impairment. After unilateral nephrectomy, circulating OPN increased significantly in parallel to the decrease in GFR. We found a direct association between OPN and other markers of renal function (serum-creatinine, homocysteine and symmetric dimethylarginine,) as well as with cardiovascular risk factors such as asymmetric dimethylarginine (r = 0.36, P = 0.0213). There is a close inverse association between GFR and circulating OPN in patients with CKD. Furthermore, OPN plasma levels correlate with established cardiovascular risk markers in patients with CKD. Assessment of renal function is important for the interpretation of OPN levels in patients with atherosclerotic disease.