Hottelart C, Achard J M, Moriniere P, Zoghbi F, Dieval J, Fournier A
Service de Néphrologie, Médecine Interne, CHU Amiens, France.
Artif Organs. 1998 Jul;22(7):614-7. doi: 10.1046/j.1525-1594.1998.06204.x.
Aldosterone suppression and subsequent hyperkalemia are well described reversible side effects of prolonged treatment with heparin. This study was designed to examine whether the discontinuous use of heparin three times a week to prevent thrombosis formation during hemodialysis sessions could also induce hypoaldosteronism and might contribute to increased predialysis kalemia in hemodialysis patients. Two different heparinization regimens were prospectively compared in a crossover study of 11 chronic hemodialysis patients. During 2 consecutive weeks, the patients were dialyzed each week with either their usual doses of unfractionated heparin (UH) (6,160 IU +/- 1,350 IU) or low molecular weight heparin (LMWH) (15 anti-Xa activity [aXa] U/kg + 5 aXa U/kg/h). In all but 2 patients, the predialysis level of plasma K+ was higher with UH than with LMWH, and the mean value was higher (5.66+/-0.83 versus 5.15+/-0.68 mM, p = 0.01) while no differences in the predialysis plasma concentrations of creatinine, phosphate, urea, and bicarbonate were observed, excluding the potential role of differences in diet and dialysis efficacy in explaining the higher plasma K+ concentration with UH. The mean plasma aldosterone to plasma renin activity (pRA) ratio was higher with LMWH than with UH (149.54+/-123.1 versus 111.91+/-86.22 pg/ng/ h, p < 0.05). Individual plasma aldosterone values were found to be correlated to pRAs both during the UH period and the LMWH period, and the slope of the positive linear relation between plasma aldosterone and pRA was lower during the UH treatment period (63 versus 105 pg/ng/h). Finally, a negative linear correlation was found between the differences in individual predialysis plasma K+ observed during the 2 protocols and the differences in the corresponding plasma aldosterone levels, suggesting a link between the higher kalemia and the lower aldosterone responsiveness to angiotensin with unfractionated heparin. Although it cannot be concluded whether or not LMWH inhibits aldosterone synthesis, should LMWH decrease aldosterone production, this side effect is 33% less marked than that of UH so that the predialysis plasma K+ levels are 10% lower. This property makes LMWH use preferable to that of UH in patients with elevated predialysis kalemia.
醛固酮抑制及随后出现的高钾血症是肝素长期治疗中已被充分描述的可逆性副作用。本研究旨在探讨每周三次间断使用肝素以预防血液透析期间血栓形成是否也会诱发醛固酮减少症,并可能导致血液透析患者透析前血钾升高。在一项对11例慢性血液透析患者的交叉研究中,前瞻性地比较了两种不同的肝素化方案。在连续2周内,患者每周分别接受其常用剂量的普通肝素(UH)(6160 IU±1350 IU)或低分子量肝素(LMWH)(15抗Xa活性单位[aXa]/kg + 5 aXa单位/kg/h)进行透析。除2例患者外,其余患者透析前血浆钾水平在使用UH时高于使用LMWH时,平均值更高(5.66±0.83对5.15±0.68 mM,p = 0.01),而透析前血浆肌酐、磷酸盐、尿素和碳酸氢盐浓度未观察到差异,排除了饮食和透析效果差异在解释UH导致较高血浆钾浓度方面的潜在作用。LMWH组的平均血浆醛固酮与血浆肾素活性(pRA)比值高于UH组(149.54±123.1对111.91±86.22 pg/ng/h,p < 0.05)。发现个体血浆醛固酮值在UH期和LMWH期均与pRA相关,且UH治疗期血浆醛固酮与pRA之间正线性关系的斜率较低(63对105 pg/ng/h)。最后,发现在两种方案期间观察到的个体透析前血浆钾差异与相应血浆醛固酮水平差异之间存在负线性相关,提示高血钾与普通肝素导致的醛固酮对血管紧张素反应性降低之间存在联系。尽管无法得出LMWH是否抑制醛固酮合成的结论,但如果LMWH减少醛固酮生成,这种副作用比UH轻33%,因此透析前血浆钾水平低10%。这一特性使得在透析前血钾升高的患者中使用LMWH优于UH。