D-Thyroxine Reduces Lipoprotein(a) Serum Concentration in Dialysis Patients CHRISTIANE BOMMER,* EGON WERLE,* INGEBORG WALTER SACK,* CHRISTINE KELLER,* FRANK GEHLEN,* CHRISTOPH WANNER, MATTHIAS NAUCK, WINFRIED MARZ HEINRICH WIELAND and JURGEN BOMMER* *Medizjnjsche Universit#{228}tsklinik, Heidelberg, Germany; Medizinische Universit#{228}tsklinik, Wiirzburg, Germany; and Medizinische Universit#{228}tsklinik, Freiburg, Germany. Abstract. Uremia raises lipoprotein(a) (Lp(a)) serum concen- tration and the risk of arteriosclerosis in dialysis patients. The treatment of high Lp(a) levels is not satisfactory today. The decrease of Lp(a) in hypothyroid patients on L-I4 therapy raised the question of whether dextro-thyroxine (D-thyroxine) reduces not only serum cholesterol, but also Lp(a) serum concentration. In a single-blind placebo-controlled study, the influence of 1)-thyroxine therapy on Lp(a) serum concentration was evaluated in 30 hemodialysis patients with elevated Lp(a) serum levels. Lp(a) was quantified in parallel by two methods, i.e., rocket immunoelectrophoresis and nephebometry, and apo(a) isoforms were determined by a sensitive immunobbot- ting technique. Regardless of the apo(a) isoforms, 6 mg/d D-thyroxine reduced elevated Lp(a) levels significantly by 27 ± 13% in 20 dialysis patients (P < 0.001) compared with 10 control subjects (-9.9 ± 8.4%). In parallel, D-thyroxine therapy significantly lowered total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and LDL cholesterollHDL cho- lesterob ratio (P < 0.01); raised 14 and 13 serum levels; and suppressed thyroid-stimulating hormone secretion without causing clinical symptoms of hyperthyroidism in any of the patients. D-Ihyroxine reduces elevated serum Lp(a) concentra- tion in dialysis patients. The effect in nondialysis patients can be expected but remains to be proven. (I Am Soc Nephrol 9: 90-96, 1998) Arteriosclerosis is accelerated in patients with end-stage renal disease (ESRD) ( 1 ). Various risk factors may be involved in the pathogenesis of arteriosclerosis in ESRD patients, such as hypertension, impaired glucose tolerance, decreased HDL, and increased serum levels of triglycerides and also of lipopro- tein(a) (Lp(a)). During the past 10 yr, Lp(a) has been recog- nized as an independent risk factor for coronary, cerebral, and peripheral arteriosclerosis in the healthy population and also in dialysis patients. In a prospective study, Cressman and cob- leagues noted a significantly higher plasma level of Lp(a) in dialysis patients with complications due to arteriosclerosis compared with patients without such complications (2). Today, treatment of elevated Lp(a) plasma concentrations is not satisfactory. A low-cholesterol diet (3), chobestyramine (4), and ( )hydroxy-(f3)methyl glutaryl-CoA reductase inhibitors (5-7) did not reduce Lp(a) plasma levels. Niacin therapy was followed by a significant decrease of Lp(a) bevels, but was poorly tolerated due to its side effects (8). Gemfibrozib (2 X 600 mg) reduced Lp(a) bevels by 27% in hyperchobesterolemic patients (9). N-Acetylcysteine also mildly reduced plasma 1ev- els of Lp(a) (10). Furthermore, sex hormones may influence Received February 17, 1997. Accepted July 16. 1997. Correspondence to Dr. lUrgen Bommer. 1 Medizin. Universithtsklinik Heidel- berg, Bergheimer Strasse 56, D-69 115 Heidelberg. Germany. 1046-6673/090i-0090$03.00/0 Journal of the American Society of Nephrobogy Copyright 0 1998 by the American Society of Nephrology Lp(a) plasma concentrations. The use of estrogen as contracep- tive (1 1), as postmenopausal hormone therapy (12), or for treat- ment of men with prostatic cancer was followed by a decrease of serum Lp(a) levels (13). Recently, bifibrol, a new lipid-lowering agent, has also been shown to lower Lp(a) concentrations by approximately 30% (14). Recent clinical observations indicated that treatment with the thyroid hormones levo-triiodothyronine (L-13) or levo- thyroxine (L-14) reduces cholesterol concentrations and also Lp(a) levels in hypothyroid patients (15-18). This raised the question of whether dextro-thyroxine (D-thyroxine), which does not have significant general metabolic effects as L-thy- roxine, but does lower serum cholesterol levels, is able to reduce Lp(a) serum concentrations. Therefore, we studied the effect of D-thyroxine on serum lipids and Lp(a) in dialysis patients with elevated Lp(a) serum concentrations. Materials and Methods Patients A total of 39 (13 women, 26 men) chronic hemodialysis patients with a basal Lp(a) concentration of more than 250 mgIL were enrolled in the study. The mean age was 58.8 ± I I .0 yr (mean ± SD), and the duration of dialysis therapy was 71 .2 ± 79.7 mo. All of the patients were routinely dialyzed for 5 h 3 times a week using Gambro AK1O (Gambro, Lund, Sweden) or Fresenius MTS 2008 C or 4008 C machines (Fresenius, Bad Homburg, Germany), and GFSI5 M, GFS l5H (Gambro, Hechingen, Germany), F6, F60, F50 diaiyzers (Frese- nius) or Renak l5U dialyzers (Kawasumi, Shmagawa KU, Tokyo,