Effect of spironolactone on K+ homeostasis and ENaC expression in lymphocytes from chronic hemodialysis patients

Luis Michea*, Antonio Vukusich, Magdalena González, Carlos Zehnder, Elisa T. Marusic

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Background. Cardiac disease is the major cause of death in hemodialysis patients (HD). It is now clear that aldosterone has deleterious effects in the cardiovascular system. In the present study, we evaluated the effects of an aldosterone-antagonist, spironolactone, on the extrarenal regulation of potassium in HD patients. Furthermore, to validate the effectiveness of the spironolactone dose-design, we measured the expression of Na+-channel (ENaC alpha subunit) in peripheral blood mononuclear cells (PBMC), before and after a two-week course of spironolactone. Methods. The study design included a two-week baseline period, followed by spironolactone treatment (50 mg three times weekly for 15 days), and by a two-week washout period and then a two-week placebo period. An oral K+ load (0.3 mEq/K+ kg body weight plus carbohydrates) was administered at the end of each period, and time-course of plasma potassium was evaluated. ENaC expression in PBMC was assessed before and after spironolactone. Results. The maximal increase in plasma potassium after the K+ carbohydrate load was: control 5.33 ± 0.88 mEq K+/L; spironolactone 5.23 ± 0.68 mEq K+/L; placebo 5.38 ± 0.61 mEq K+/L (N = 9). No patients developed hyperkalemia during the spironolactone treatment period. ENaC expression was significantly higher in all six HD patients studied, compared to control subjects (P < 0.05). Treatment with spironolactone in HD patients reduced alpha subunit mRNA expression to values similar to those of normal subjects. Conclusion. Spironolactone may be considered for the treatment of selected chronic HD patients. The effect of the drug on a known target of aldosterone, the ENaC, demonstrates the effectiveness of the drug to block aldosterone effects in nonepithelial tissues.

Original languageEnglish
Pages (from-to)1647-1653
Number of pages7
JournalKidney International
Issue number4
StatePublished - Oct 2004

Bibliographical note

Funding Information:
We would like to thank the staff and patients of the Renal Outpatient Dialysis Unit, Clínica Dávila, and especially to Ms. Cecilia Avalos, who undertook the patients' drug administration and blood samples. We also want to thank Drs. J. Morales and A. Fierro for their helpful comments on the study design. This work was supported by grant no. MED 004–03 from University Los Andes and grants from Fondo Nacional InvestigaciÓn Científica, FONDECYT, nos. 1040338 and 1010185.


  • Aldosterone
  • Cardiovascular
  • Hyperkalemia
  • Renal disease
  • Sodium channel


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