Hemodialysis (HD) patients are frequently in a state of increased oxidative stress, and hyperglycemia appears to be a major factor. We recently found that oxidized human serum albumin (HSA) is a reliable marker of oxidative stress in HD patients. However, the issue of whether oxidized HSA is associated with the progression of oxidative stress in HD patients with or without diabetes is not clear. In the present study, we examined the effect of a qualitative modification of HSA in HD patients with or without diabetes. Blood samples from 10 HD patients with diabetes, 7 HD patients without diabetes, and 10 healthy age-matched controls were examined. The increase in plasma protein carbonyl content and advanced glycation endproducts (AGEs) in HD patients was largely due to an increase in the levels of oxidized HSA. Furthermore, these increases were greatest in HD patients with diabetes. Purified HSA from HD patients (non-DM-HSA) was carbonylated and AGE-modified. The amount of modified HSA was the highest in HD patients with diabetes (DM-HSA). Carboxy methyl lysine (CML)-modified HSA triggered a neutrophil respiratory burst, and this activity was closely correlated with the increase in the CML/HSA ratio. These findings indicate that uremia plays an important role in the progression of oxidative stress in HD patients via an increase in CML-modified HSA. They also indicate that diabetic complications further exacerbate the progression of oxidative stress by further increasing the amount of these modified HSA molecules.
De Lemos JA, Hillis LD : Diagnosis and management of coronary artery disease in patients with end-stage renal disease on hemodialysis. J Am Soc Nephrol 1996; 7: 2044–2054.
The Diabetes Control and Complications Trial Research Group : The effect of intensive treatment of diabetes on the development and progression of long term complications in insulin dependent diabetes mellitus. N Engl J Med 1993; 329: 977–986.
Nitta K, Akiba T, Uchida K, et al: Left ventricular hypertrophy is associated with arterial stiffness and vascular calcification in hemodialysis patients. Hypertens Res 2004; 27: 47–52.
Stenvinkel P, Alvestrand A : Inflammation in end-stage renal disease: sources, consequences, and therapy. Semin Dial 2002; 15: 329–337.
Stenvinkel P : Inflammatory and atherosclerotic interactions in the depleted uremic patient. Blood Purif 2001; 19: 53–61.
Himmelfarb J : Linking oxidative stress and inflammation in kidney disease: which is the chicken and which is the egg? Semin Dial 2004; 17: 449–454.
Baynes JW : Perspectives in diabetes: role of oxidative stress in development of complications in diabetes. Diabetes 1991; 40: 405–412.
Wang AY, Woo J, Wang M, et al: Association of inflammation and malnutrition with cardiac valve calcification in continuous ambulatory peritoneal dialysis patients. J Am Soc Nephrol 2001; 12: 1927–1936.
Anraku M, Kitamura K, Shinohara A, et al: Intravenous iron administration induces oxidation of serum albumin in hemodialysis patients. Kidney Int 2004; 66: 841–848.
Papanastasiou P, Grass L, Rodela H, Patrikarea A, Oreopoulos D, Diamandis EP : Immunological quantification of advanced glycosylation end-products in the serum of patients on hemodialysis. Kidney Int 1994; 46: 216–222.
Witko-Sarsat V, Friedlander M, Nguyen Khoa T, et al: Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. J Immunol 1998; 161: 2524–2532.
Makita Z, Randoff S, Rayfield EJ, et al: Advanced glycosylation end products in patients with diabetic nephropathy. New Engl J Med 1991; 19: 836–842.
Makita Z, Bucala R, Rayfield RJ, et al: Reactive glycosylation endproducts in diabetic uremia and treatment of renal failure. Lancet 1994; 343: 1519–1522.
Watanabe H, Yamasaki K, Kragh-Hansen U, et al: In vitro and in vivo properties of recombinant human serum albumin from Pichia pastoris purified by a method of short processing time. Pharm Res 2001; 18: 1775–1781.
Duncombe WG : The colorimetric micro-determination of non-esterified fatty acid in plasma. Clin Chim Acta 1964; 10: 122–125.
Sogami M, Nagoka S, Era S, Honda M, Noguchi K : Resolution of human mercapt- and nonmercaptalbumin by high-performance liquid chromatography. Int. J. Pept. Protein Res 1984; 24: 96–103.
Era S, Hamaguchi T, Sogami M, et al: Further studies on the resolution of human mercapt- and nonmercaptalbumin and on human serum albumin in the elderly by high-performance liquid chromatography. Int. J. Pept. Protein Res 1985; 3: 435–442.
Climent I, Tsai L, Levine RL : Derivatization of gamma-glutamyl semialdehyde residues in oxidized proteins by fluoresceinamine. Anal Biochem 1989; 182: 226–232.
Shacter E, Williams JA, Lim M, Levine RL : Differential susceptibility of plasma proteins to oxidative modification: examination by Western blot immunoassay. Free Radic Biol Med 1994; 17: 429–437.
Westwood ME, McLellan AC, Thornalley PJ : Receptor-mediated endocytic uptake of methylglyoxal-modified serum albumin. Competition with advanced glycation end product-modified serum albumin at the advanced glycation end product receptor. J Biol Chem 1994; 269: 32293–32298.
Nagai R, Horiuchi S : Application of monoclonal antibody libraries for the measurement of glycation adducts. Biochem Soc Trans 2003; 31: 1438–1440.
Nakajima H, Takenaka M, Kaimori JY, et al: Activation of the signal transducer and activator of transcription signaling pathway in renal proximal tubular cells by albumin. J Am Soc Nephrol 2004; 15: 276–285.
Ivanov AI, Korolenko EA, Korolik EV, et al: Chronic liver and renal diseases differently affect structure of human serum albumin. Arch Biochem Biophys 2002; 408: 69–77.
Tojo A, Onozato ML, Kurihara H, et al: Angiotensin II blockade restores albumin reabsorption in the proximal tubules of diabetic rats. Hypertens Res 2003; 26: 413–419.
Goldwasser P, Feldman J : Association of serum albumin and mortality risk. J Clin Epidemiol 1997; 50: 693–703.
Ishimitsu T, Murayama N, Meguro T, et al: Urinary excretions of albumin and type IV collagen in normotensive and hypertensive subjects. Hypertens Res 2000; 23: 459–466.
Kohara K, Tabara Y, Tachibana R, Nakura J, Miki T : Microalbuminuria and arterial stiffness in a general population: the Shimanami Health Promoting Program (J-SHIPP) study. Hypertens Res 2004; 27: 471–477.
Terawaki H, Yoshimura K, Hasegawa T, et al: Oxidative stress is enhanced in correlation with renal dysfunction: examination with the redox state of albumin. Kidney Int 2004; 66: 1988–1993.
Shimada H, Kitamura K, Anraku M, et al: Effect of telmisartan on ambulatory blood pressure monitoring, plasma brain natriuretic peptide, and oxidative status of serum albumin in hemodialysis patients. 2005; 28: 987–994.
Foley RN, Parfrey PS, Sarnak MJ : Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998; 32: S112–S119.
Shaklai N, Garlick RL, Bunn HF : Nonenzymatic glycosylation of human serum albumin alters its conformation and function. J Biol Chem 1984; 259: 3812–3817.
Woodside JV, Yarnell JW, McMaster D, et al: Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia double-blind, randomized, factorial-design, controlled trial. Am J Clin Nutr 1998; 67: 858–866.
Dean RT, Hunt JV, Grant AJ, Yamamoto Y, Niki E : Free radical damage to proteins the influence of the relative localization of radical generation, antioxidants, and target proteins. Free Radic Biol Med 1991; 11: 161–168.
Dean RT, Fu S, Stocker R, Davies MJ : Biochemistry and pathology of radical-mediated protein oxidation. Biochem J 1997; 324: 1–18.
Collison KS, Parhar RS, Saleh SS, et al: RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs). J Leukoc Biol 2002; 71: 433–444.
About this article
Cite this article
Mera, K., Anraku, M., Kitamura, K. et al. Oxidation and Carboxy Methyl Lysine-Modification of Albumin: Possible Involvement in the Progression of Oxidative Stress in Hemodialysis Patients. Hypertens Res 28, 973–980 (2005). https://doi.org/10.1291/hypres.28.973
- hemodialysis patients
- oxidative stress
- human serum albumin
- neutrophil burst
Influence of oxidative stress on vascular calcification in the setting of coexisting chronic kidney disease and diabetes mellitus
Scientific Reports (2020)
Mode of renal replacement therapy determines endotoxemia and neutrophil dysfunction in chronic kidney disease
Scientific Reports (2016)
Elucidation of the Mechanism Responsible for the Oxidation of Serum Albumin and Its Application in Treating Oxidative Stress-related Diseases
YAKUGAKU ZASSHI (2014)
Oxidatively-modified and glycated proteins as candidate pro-inflammatory toxins in uremia and dialysis patients
Amino Acids (2007)