High, Low Potassium Raise Death Risk in Men with CKD

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Hypo- and hyperkalemia are associated with higher mortality in male patients with chronic kidney disease (CKD) but not yet on dialysis, but this association varies by race, a study found.

Hypokalemia confers a greater risk of death for blacks than whites, whereas hyperkalemia increases the risk of death among whites but not blacks.

In addition, the study showed that hypokalemia is associated with faster CKD progression independent of race.

“Hyperkalemia management may warrant race-specific consideration, and hypokalemia correction may slow CKD progression,” the authors concluded.

Researchers led by Csaba P. Kovesdy, MD, of the University of Virginia in Charlotte and the Salem Veterans Affairs Medical Center in Salem, Va., studied pre-dialysis mortality and slopes of estimated glomerular filtration rate (eGFR) in a cohort of 1,227 male CKD patients (933 whites and 294 blacks). The investigators defined hypokalemia as a serum potassium level below 3.8 mEq/L in the study population overall and in whites, and as a level below 3.7 mEq/L in blacks. They defined hyperkalemia as a serum potassium level above 5.5 mEq/L in all three groups. A level of 3.8-5.5 mEq/L served as the reference value for the study population overall and for whites; a level of 3.7-5.5 mEq/L served as the reference for blacks.

Compared with their reference groups, blacks with hypokalemia had a nearly threefold increased risk of all-cause mortality and whites with hypokalemia had an approximately 1.5 times increased risk in fully adjusted models, the researchers reported in Nephron Clinical Practice (2011;120:8-16). Hyperkalemia in blacks was associated with no increased risk of all-cause mortality, but hyperkalemia in whites was associated with a roughly 1.5 times increased risk in fully adjusted models.

In the study population overall, each 1 mEq/L decrease in serum potassium was associated with a 0.13 mL/min/1.73 m2 per year decrease in eGFR after adjusting for potential confounders.

“The potential presence of biological differences in potassium homeostasis in blacks vs. whites raises the possibility that the lack of association between hyperkalemia and mortality in blacks in our study may be related to more effective bodily defense mechanisms against higher potassium levels and/or its electrophysiological effects in these patients,” the authors wrote.

A potential race-specific differential impact of hyperkalemia on clinical outcomes in CKD patients not on dialysis could be important, Dr. Kovesdy's team noted. Greater tolerance of elevated serum potassium levels could enable more liberal use of treatments that raise serum potassium levels in black patients, such as ACE inhibitors, angiotensin receptor blockers, aldosterone antagonists, or potassium-sparing diuretics.

“To the best of our knowledge, ours is the first study to examine race-specific clinical outcomes associated with serum potassium levels,” the authors wrote. They also observed that prior to their study, low potassium had not been previously described as a risk factor for progressive CKD.

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