Saudan Patrick, Mach Francois, Perneger Thomas, Schnetzler Bruno, Stoermann Catherine, Fumeaux Zina, Rossier Michel, Martin Pierre-Yves
Division of Nephrology, Department of Medicine, University Hospital, Geneva Medical School, Geneva, Switzerland.
Nephrol Dial Transplant. 2003 Nov;18(11):2359-63. doi: 10.1093/ndt/gfg388.
Prevention of cardiovascular diseases is essential in chronic haemodialysis patients. Recently, low-dose spironolactone has been shown to decrease cardiovascular mortality in patients with severe heart failure. However, since haemodialysis patients are prone to hyperkalaemia, a known side effect of spironolactone, this treatment is not used in this population. We performed a study to assess whether low-dose spironolactone (3 x 25 mg/week) could be administered without inducing hyperkalaemia in haemodialysis patients.
The study design included a 2-week baseline period, followed by a 4-week treatment period in which doses of spironolactone were started at 12.5 mg three times/week for 2 weeks, then increased to 25 mg three times/week, and followed by a 2-week wash-out period. Fourteen patients receiving low-dose spironolactone after each dialysis were compared with 21 haemodialysis patients (control group).
Low-dose spironolactone did not change mean serum potassium (4.9 +/- 0.7 vs 4.9 +/- 0.3 mmol/l: control). The mean plasma canrenone level induced by administration of spironolactone 25 mg three times/week in the 14 treated patients was 13 +/- 5.3 ng/ml. Serum aldosterone was not significantly modified by the administration of spironolactone in these patients [before, median 0.35; interquartile range (IQR) 0.11-2.83 nmol/l vs after, median 0.22; IQR 0.12-0.60 nmol/l, NS]. Dietary potassium intake and the use of ion-exchange resin, angiotensin-converting enzyme inhibitors and beta-blockers were similar for the two groups throughout the study.
This non-randomized and non-blinded study shows that administration of 25 mg spironolactone thrice weekly is not associated with an increased frequency of hyperkalaemia in haemodialysis patients when they are carefully monitored. More studies are required, however, before concluding that spironolactone administration is safe in the chronic haemodialysis population.
预防心血管疾病对于慢性血液透析患者至关重要。最近,已证明低剂量螺内酯可降低重度心力衰竭患者的心血管死亡率。然而,由于血液透析患者易发生高钾血症,而高钾血症是螺内酯已知的副作用,因此该治疗方法未在这一人群中使用。我们进行了一项研究,以评估低剂量螺内酯(3×25毫克/周)在血液透析患者中使用时是否不会诱发高钾血症。
研究设计包括为期2周的基线期,随后是为期4周的治疗期,在此期间,螺内酯剂量开始为12.5毫克,每周三次,持续2周,然后增加至25毫克,每周三次,随后是为期2周的洗脱期。将每次透析后接受低剂量螺内酯治疗的14名患者与21名血液透析患者(对照组)进行比较。
低剂量螺内酯未改变平均血清钾水平(4.9±0.7对4.9±0.3毫摩尔/升:对照组)。在14名接受治疗的患者中,每周三次给予25毫克螺内酯所诱导的平均血浆坎利酮水平为13±5.3纳克/毫升。在这些患者中,给予螺内酯后血清醛固酮没有显著改变[给药前,中位数0.35;四分位间距(IQR)0.11 - 2.83纳摩尔/升,给药后,中位数0.22;IQR 0.12 - 0.60纳摩尔/升,无显著性差异]。在整个研究过程中,两组的饮食钾摄入量以及离子交换树脂、血管紧张素转换酶抑制剂和β受体阻滞剂的使用情况相似。
这项非随机、非盲法研究表明,当对血液透析患者进行仔细监测时,每周三次给予25毫克螺内酯与高钾血症发生率增加无关。然而,在得出螺内酯给药在慢性血液透析人群中安全的结论之前,还需要更多的研究。