Hyperkalemia clinical significance

Fixed combinations of thiazides and loop diuretics with potassium and of thiazides with beta-blockers serve little useful purpose and can in fact do harm. Combinations of thiazides and loop diuretics with potassium-sparing diuretics serve the needs of the small minority of patients who develop clinically significant hypokalemia when given diuretics alone, or in whom hypokalemia is particularly risky. In fact, these combinations are much too widely used, and since individual needs vary so much there is a spectrum of risk, ranging from hypokalemia to hyperkalemia (SEDA-10, 370) (SEDA-10, 371). 

In addition to vasodilatory responses, PGs have a number of other effects in the kidney. For example, PGs stimulate adenylate cyclase in juxtaglomerular cells, resulting in an increase in cAMP production this, in turn, increases renin release. Renin stimulates the release of aldosterone, which increases renal tubular secretion of potassium (Stillman Schlesinger 1990). PGs also enhance tubular excretion of sodium and water (Patrono Dunn 1987). By causing these effects in the kidneys, PGs can alter electrolyte homeostasis. Therefore, other renal side-effects of NSAID therapy can include hyperkalemia, hypernatremia and edema. Often these metabolic changes are not observed in individuals with normal renal function, but in the presence of pre-existing disease they can become clinically significant. 

Heparin is known to inhibit aldosterone synthesis. This is not considered clinically significant. However the effects on aldosterone may lead to hyperkalemia and metabolic abnormalities with long term therapy. 

B. Specific drugs and antidotes. When clinically significant hypocalcemia is present, administer intravenous calcium gluconate (see p 424), 10-20 mL (children 0.2-0.3 mL/kg), and monitor ionized calcium levels and titrate further doses as needed. Treat hypomagnesemia with intravenous magnesium sulfate, 1-2 g given over 10-15 min (children 25-50 mg/kg diluted to less than 10 mg/mL). Treat hyperkalemia with intravenous calcium and other usual measures (p 37). 

Alderman MH, Filler LB, Ford CE, Probstfield JL, Oparil S, Cushman WC, et al. Clinical significance of incident hypokalemia and hyperkalemia in treated hypertensive patients in the antihypertensive and Hpid-lowering treatment to prevent heart attack trial. Hypertension 2012 59 926-33. 

In conclusion, hyperkalemia associated with the use of traditional NSAIDs or the coxibs becomes a clinical risk in individuals with significantly decreased renal function and/or in those with the combination of decreased renal function and use of an ACE inhibitor. 

Although it is beyond the scope of this chapter, a more recently addressed question is whether intervention in the RAS system by adding a mineralo-corticoid receptor antagonist is associated with beneficial effects. Several small, short-term studies have been published [59-64] but clearly further documentation is needed before a possible clinical role of this intervention can be assessed. Hyperkalemia is a major concern, but in a recent study by Epstein et al. [65], where coadministration of eplerenone and ACE-1 over 12 weeks resulted in significant reduction in albuminuria, no significant increases in hyperkalemia was observed. 

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