Response to Unexpected Therapeutic Response to Spironolactone: A Prospective Debate on Aldosterone and Potassium Ion in Hypertension
Delgado-Almeida1 raises interesting issues, notably the complexity of potassium balance and the crudity of serum potassium measurements. Most clinicians and investigators measure serum potassium as a reflection of aldosterone activity because it is readily available; their concern about red-cell potassium is usually restricted to its tendency to leak into the plasma after the sample is drawn. The principal unknown in Chapman’s cohort was not so much the amount or distribution of potassium but the amount of aldosterone in subjects who did or did not respond to spironolactone. Of course, even that metric would require consideration of electrolyte intake. Furthermore, it is by no means certain that spironolactone lowered blood pressure by its effects on mineralocorticoid receptors; its metabolite canrenone might have lowered pressure by its effect on ATP-ases. Perhaps that is what Delgado-Almeida1 was referring to when he mentioned cellular Na/K handling.
The most frustrating aspect of clinical research is the inability to measure every parameter of possible relevance to the question at hand. For example, I am interested in the relationships among aldosterone, its classical and nonclassical secretagogues, its traditional and recently recognized effects, and the metabolic syndrome. My colleagues have additional interests in genetics and sleep disorders. Delgado-Almeida1 would like to know more about potassium distribution. National Institutes of Health would insist on including subjects from several different populations. Industry would want the study to involve patent-protected drugs. Statisticians would insist on large numbers of subjects, especially because they would apply corrections for all of the measured variables. At this point, I can only dream that such a study will be performed. If it is, the ideas of Delgado-Almeida1 undoubtedly will be considered.