Reduction of Advanced Glycation End Product Levels by On-Line Hemodiafiltration in Long-Term Hemodialysis Patients Chun-Liang Lin, MD, Chiu-Ching Huang, MD, Chun-Chen Yu, MD, Huan-Yu Yang, MD, Feng-Rong Chuang, MD, and Chih-Wei Yang, MD ● Background: Advanced glycation end products (AGEs) are thought to be involved in many complications of end-stage renal disease. This study analyzed serum AGE level reduction rates and corresponding long-term changes in serum levels among different dialysis modes. Methods: Eighty-one patients with chronic uremia were divided into 3 groups receiving conventional hemodialysis (HD), high-flux HD, or on-line hemodiafiltration (HDF). Serum AGE levels were measured by competitive enzyme-linked immunosorbent assay predialysis and postdialy- sis and after 6 months. Additionally, AGE clearance was measured in 11 uremic patients treated with alternative high-flux HD and on-line HDF. Results: Although predialysis serum AGE levels were similar, postdialysis levels were significantly lower in patients treated with on-line HDF (35.4  4.2 g/mL) compared with those treated with conventional HD (82.2  11.4 g/mL; P  0.003), but not high-flux HD (56.7  5.9 g/mL; P  0.15). The serum AGE level reduction rate in on-line HDF (61.5%  4.2%) was significantly greater than that in conventional HD (20.5%  2.4%; P < 0.001) and high-flux HD patients (40.4%  2.7%; P  0.049). AGE clearance was increased 50% with on-line HDF compared with high-flux HD, reaching borderline significance (P  0.07). In a 6-month study, predialysis serum AGE levels were significantly lower in patients treated with on-line HDF compared with those treated with conventional and high-flux HD. Conclusion: On-line HDF may provide an improved form of treatment that achieves significantly better AGE level reduction than high-flux HD and conventional HD. Uremic patients treated with on-line HDF for longer than 6 months achieved a significant reduction in predialysis serum AGE levels. Am J Kidney Dis 42:524-531. © 2003 by the National Kidney Foundation, Inc. INDEX WORDS: On-line hemodiafiltration (HDF); advanced glycation end products (AGEs); end-stage renal disease (ESRD). A DVANCED GLYCATION end products (AGEs) are produced by a nonenzymatic reaction known as the Maillard reaction. 1 Many studies have speculated that AGEs may represent a novel class of uremic toxins with significant implications for long-term dialysis-related patho- logical states. 2,3 AGEs currently are believed to include diverse structures. In uremic patients, the increase in AGE levels is even more marked than in patients with diabetes mellitus (DM) and is associated with various tissue disorders, includ- ing vascular damage, dyslipidemia, and  2 - microglobulin amyloidosis. 4,5 AGE-modified pro- teins are thought to have a role in normal tissue remodeling. These accumulations may lead to various forms of tissue damage, including athero- sclerosis, 6 diabetic nephropathy, 7 dialysis-related amyloidosis, 8 and Alzheimer’s disease. 9 Addition- ally, increasing evidence exists that reactive se- rum AGEs may be a key component of the uremic middle molecule, which can cause tissue damage and presumably mediate these complica- tions. 10 Improving quality of life and preventing long- term dialysis-related complications are critical for uremic patients on hemodialysis (HD) therapy. An increasing body of evidence shows that modes of dialysis treatment are important in amyloid- osis development. 11 On-line hemodiafiltration (HDF) is a method that combines the convective component of hemofiltration and diffusive HD in which a toxin- and pyrogen-free dialysis fluid is used for fluid substitution. On-line HDF offers improved solute clearance for both low- and high-molecular-weight uremic toxins by enhanc- ing convective clearance through highly perme- able membranes. 12 Additionally, HDF has proven to be more effective in preventing dialysis- related amyloidosis, uremic neuropathy, and joint pain. 13 As for other uremic toxic substances, HD From the Division of Nephrology, Chang Gung Memorial Hospital, Chiayi; and the Department of Nephrology, Chang Gung Memorial Hospital, Taipei, Taiwan. Received December 30, 2002; accepted in revised form May 20, 2003. Supported in part by grant no. CMRPG6001 from the Chang Gung Memorial Hospital Medical Research Pro- gram. Address reprint request to Chih-Wei Yang, MD, Depart- ment of Nephrology, Chang Gung Memorial Hospital, 199, Tun-Hwa North Rd, Taipei 105, Taiwan. E-mail: cwyang@ms1.hinet.net © 2003 by the National Kidney Foundation, Inc. 0272-6386/03/4203-0008$30.00/0 doi:10.1016/S0272-6386(03)00747-9 American Journal of Kidney Diseases, Vol 42, No 3 (September), 2003: pp 524-531 524