Soluble receptor for advanced glycation end products in patients with decreased renal function

Background: Advanced glycation end products (AGEs) accumulate in patients with decreased renal function and exert various toxic effects through the receptor for AGEs (RAGE). Soluble RAGE (sRAGE) is a naturally occurring inhibitor of AGE-RAGE action. The aim of the study is to describe the relationship of sRAGE to renal function and dialysis modalities. Methods: The studied group consisted of 81 patients: 25 patients with various degrees of decreased renal function, 20 long-term hemodialysis (HD) patients, 15 peritoneal dialysis (PD) patients, and 21 healthy age-matched subjects. sRAGE was assessed immunochemically (enzyme-linked immunosorbent assay), and routine biochemical parameters were measured by means of certified methods. Results: sRAGE level correlates positively with serum creatinine concentration (r=0.50; P<0.05), and its relationship to creatinine clearance is hyperbolic. sRAGE levels are elevated significantly, mainly in patients with end-stage renal disease (3,119.0 +/- 968.4 pg/mL in HD patients and 3,652.7 +/- 1,677.7 pg/mL in PD patients versus 1,405.1 +/- 426.1 pg/mL in controls; both P<0.001 versus controls). In PD patients, sRAGE is detectable in spent dialysate (median, 75.8 pg/mL), correlates with its serum levels (r=0.67; P<0.05), and is related to protein losses in dialysate. In HD patients, sRAGE levels increase by 50% (P<0.001) from 0 to 15 minutes during both HD and hemodiafiltration, and then decrease until the end of the session. Conclusion: Serum sRAGE levels increase in patients with decreased renal function, mainly patients with end-stage renal disease. It remains to be elucidated whether the increase is caused just by decreased renal function or whether sRAGE is upregulated to protect against toxic effects of AGEs.