Heparin-induced aldosterone suppression and hyperkalemia

  • James R. Oster
    Requests for reprints should be addressed to James R. Oster, MD, Professor of Medicine, Associate Chief, Medical Service, VA Medical Center, 1201 NW 16th Street, Miami, Florida 33125.
    From the Medical and Research Services, Department of Veterans Affairs Medical Center and the Department of Medicine, University of Miami School of Medicine, Miami, Florida, USA
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  • Irwin Singer
    From the Medical and Research Services, Department of Veterans Affairs Medical Center and the Department of Medicine, University of Miami School of Medicine, Miami, Florida, USA
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  • Lawrence M. Fishman
    From the Medical and Research Services, Department of Veterans Affairs Medical Center and the Department of Medicine, University of Miami School of Medicine, Miami, Florida, USA
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      To review the effects of heparin and heparinoid compounds on aldosterone physiology and associated induction of hyperkalemia.

      materials and methods

      A comprehensive literature search (of human and animal data) was carried out by computer and by using reference citations from primary sources.


      Heparin and its congeners are predictable, potent inhibitors of aldosterone production. This inhibitory effect is specific for the zona glomerulosa; other corticosteroids are not affected. Aldosterone suppression occurs within a few days of initiation of therapy, is reversible, and is independent of either anticoagulant effect or route of administration. Decreases in aldosterone levels may occur with heparin dosages as low as 5,000 U bid. The most important, but probably not the only mechanism of aldosterone inhibition appears to involve reduction in both the number and affinity of the angiotensin-II receptors in the zona glomerulosa. Prolonged use of heparin causes marked reduction in the width of the adrenal zona glomerulosa.


      Aldosterone suppression results in natriuresis and less predictably in decreased excretion of potassium. Greater than normal serum potassium levels occur in about 7% of patients, but marked hyperkalemia generally requires the presence of additional factors perturbing potassium balance (in particular, renal insufficiency, diabetes mellitus, or the use of certain medications). Heparin-induced increases in serum potassium need to be better anticipated by clinicians. Serum potassium levels should be monitored periodically in patients being given heparin for 3 or more days, and in patients at relatively high risk for hyperkalemia, the monitoring interval should probably be no greater than 4 days.
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