High Lipoprotein (a) Levels in Chronic Hemodialysis Patients are Closely Related to the Acute Phase Reaction

Summary

To study the mechanism underlying the high lipoprotein (a) [Lp(a)] level in uremic patients on chronic hemodialysis, we investigated the levels of Lp(a), acute phase reactants (C-reactive protein and sialic acid), and interleukin-6 (IL-6) in 54 dialysis patients. The mean [95% Cl] Lp(a) level was increased in the hemodialysis patients compared with the 30 controls (30 [25-36] vs. 18 [14-23] mg/dl, p <0.005). Among dialysis patients, 46% had an Lp(a) level >30 mg/dl, which was significantly higher than the percentage in the control group (17%). The levels of C-reactive protein, sialic acid, and IL-6 were also increased in dialysis subjects compared with controls (200 [134-299] vs. 37 [24-58] μg/dl, p <0.0001; 63 [59-66] vs. 54 [52-56] mg/dl, p <0.002; and 9.2 [7.8-11] vs. 5.5 [5.0-6.1]pg/ml, p <0.0005, respectively). The Lp(a) level was positively correlated with that of C-reactive protein (r = 0.415, p <0.002), sialic acid (r = 0.426, p <0.002), and IL-6 (r = 0.298, p<0.05) in the hemodialysis patients, but not in the controls or non-dialysis uremic patients. The Lp(a) level in the dialysis patients was also positively correlated with activation markers of coagulation (thrombin-antithrombin III complex and plasmin-α₂-plasmin inhibitor complex, p <0.005). These results indicate that the Lp(a) level is closely related to the acute phase reaction and hypercoagulability in chronic hemodialysis patients.

• References

• 1 McLean JW, Tomlinson JE, Kuang WJ, Eaton DL, Chen EY, Fless GM, Scanu AM, Lawn RM. cDNA sequence of human apolipoprotein (a) is homologous to plasminogen. Nature 1987; 300: 132-137
• 2 Scott J. Lipoprotein (a). Thrombotic and atherogenic Brit Med J 1991; 303: 663-664
• 3 Dahlen GH. Lp(a) lipoprotein in cardiovascular disease. Atherosclerosis 1994; 108: 111-126
• 4 Parra HJ, Mezdour H, Cachera C, Dracon M, Tacquet A, Fruchart JC. L(a) lipoprotein in patients with chronic renal failure treated by hemodialysis. Clin Chem 1987; 33: 721
• 5 Kandoussi A, Cachera C, Pagniez D, Dracon M, Fruchart JC, Tacquet A. Plasma level of lipoprotein Lp(a) is high in predialysis or hemodialysis, but not in CAPD. Kidney Int 1992; 42: 424-425
• 6 Docci D, Manzoni G, Bilancioni R, Delvecchio C, Capponcini C, Baldrati L, Neri L, Feletti C. Serum lipoprotein (a) and coronary artery disease in uremic patients on chronic hemodialysis. Int J Artif Organs 1994; 17: 41-45
• 7 Cressman MD, Hoogwerf BJ, Schreiber MJ, Cosentino FA. Lipid abnormalities and end-stage renal disease: implications for atherosclerotic cardiovascular disease. Miner Electrolyte Metab 1993; 19: 180-185
• 8 Maeda S, Abe A, Seishima M, Makino K, Noma A, Kawade M. Transient changes of serum lipoprotein (a) as an acute phase protein. Atherosclerosis 1989; 78: 145-150
• 9 Kario K, Matsuo T, Imiya M, Kayaba K, Kuroda T, Nago N, Matsuo H, Shimada K. Close relation between lipoprotein (a) levels and atherothrombotic disease in Japanese subjects >75 years of age. Am J Cardiol 1994; 73: 1187-1190
• 10 Kishimoto T. The biology of interleukin-6. Blood 1989; 74: 1-10
• 11 Ikeda U, Ohkawa F, Seino Y, Yamamoto K, Hidaka Y, Kasahara T, Kawai T, Shimada K. Serum interleukin 6 levels become elevated in acute myocardial infarction. J Mol Cell Cardiol 1992; 24: 579-584
• 12 Herbelin A, Urena P, Nguyen AT, Zingraff J, Descamps-Latscha B. Elevated circulating levels of interleukin-6 in patients with chronic renal failure. Kidney Int 1991; 39: 954-960
• 13 Cavaillon JM, Poignet JL, Fitting C, Delons S. Serum interleukin-6 in longterm hemodialysed patients. Nephron 1992; 60: 307-313
• 14 Nakahama H, Tanaka Y, Shirai D, Miyazaki M, Imai N, Yokokawa T, Okada M, Kubori S. Plasma interleukin-6 levels in continuous ambulatory peritoneal dialysis and hemodialysis patients. Nephron 1992; 61: 132-134
• 15 Wade DP, Clarke JG, Lindahl GE, Liu AC, Zysow BR, Meer K, Schwartz K, Lauw RM. Genetic influences on lipoprotein(a) concentration. Biochem Soc Trans 1993; 21: 499-502
• 16 Kario K, Matsuo T, Kobayashi H, Matsuo M, Yamamoto K, Sakurai G, Baba M. Rapid quantitative evaluation of plasma D-dimer levels in thrombotic states using an automated latex photometric immunoassay. Thromb Res 1992; 66: 179-189
• 17 Docci D, Bilancioni R, Buscaroli A, Baldrati L, Capponcini C, Mengozzi S, Turci F, Feletti C. Elevated serum levels of C-reactive protein in hemodialysis patients. Nephron 1990; 56: 364-367
• 18 Haeffner-Cavaillon N, Cavaillon JM, Ciancioni C, Bade F, Delons S, Kazatchkine MD. In vivo induction of interleukin-1 during hemodialysis. Kidney Int 1989; 35: 1212-1218
• 19 Lonnemann G, Van Der Meer JW M, Cannon JG, Dinarello CA, Koch KM, Granollera C, Deschodt G, Schaldon S. Induction of tumor necrosis factor during extracorporeal blood purification. N Engl J Med 1987; 317: 963-964
• 20 Herbelin A, Nguyen AT, Zingraff J, Urena P, Descamps-Latscha B. Influence of uremia and hemodialysis on circulating interleukin-1 and tumor necrosis factor a. Kidney Int 1990; 37: 116-125
• 21 Shalaby MR, Waade A, Espevik T. Cytokine regulation of interleukin 6 production by human endothelial cells. Cell Immunol 1989; 121: 372-382
• 22 McIntosh JK, Jablons DM, Mule JJ, Nordan RP, Rudikoff S, Lotze MT, Rosenberg SA. In vivo induction of IL-6 by administration of exogenous cytokines and detection of de novo serum levels of IL-6 in tumor-bearing mice. J Immunol 1989; 143: 162-167
• 23 Kario K, Matsuo T, Yamada T, Nakao K, Shimano C, Matsuo M. Factor VII hyperactivity in chronic dialysis patients. Thromb Res 1992; 67: 105-113
• 24 Eberst ME, Berkowitz LR. Hemostasis in renal disease: pathophysiology and management. Am J Med 1994; 96: 168-179