Original Investigation
Pathogenesis and Treatment of Kidney Disease and Hypertension
Soluble Receptor for Advanced Glycation End Products in Patients With Decreased Renal Function

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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.

Section snippets

Patients and Controls

sRAGE was studied in patients with chronic kidney diseases and various degrees of decreased renal function: patients with end-stage renal disease, hemodialysis (HD) and peritoneal dialysis (PD) patients, and healthy controls. Detailed characteristics of patients are listed in Table 1. All patients were in stable clinical status at the time of the study, without signs of acute infection or acute cardiac problems.

Results

In patients with chronic kidney diseases and various degrees of decreased renal function, sRAGE level correlates significantly positively with serum creatinine concentration (r = 0.50; P < 0.05; Fig 1) and negatively with reciprocal value of estimated glomerular filtration rate (r = 0.53; P < 0.05) because the relationship to creatinine clearance is hyperbolic (Fig 2). In 5 patients with nephropathy, sRAGE also was detectable in urine samples (25, 64, 1,027, 54, and 102 pg/mL), and 4 of these

Discussion

This study shows for the first time that sRAGE levels increase in patients with decreased renal function independently of the cause of kidney disease. However, some influence of the kidney also was supposed in previous studies that focused on other diseases because patients with impaired renal function were not included.17, 20 sRAGE probably is filtered (at least partially) by renal glomeruli and then processed by renal tubules. In patients with heavy proteinuria, sRAGE subsequently is present

Acknowledgment

The authors thank Dr Soukupová, Dr Benáková, and the nurses and laboratory technicians for their assistance.

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    Support: Supported by grant from the Internal Grant Agency of the Czech Ministry of Health NR/8094-3. Potential conflicts of interest: None.

    Originally published online as doi:10.1053/j.ajkd.2005.12.028 on January 30, 2006.

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