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Glomerular filtration strong predictor of hyperkalemia risk in certain patients with chronic kidney disease, study shows

Tuesday, October 13 2009 | Comments

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What's This? Regardless of the antihypertensive treatment used, researchers found that the risk of hyperkalemia is inversely related to glomerular filtration rate (GFR) and body mass index (BMI) in nondiabetic black patients who have hypertensive chronic kidney disease.

They used information from the AASK clinical trial to understand the incidence and factors associated with hyperkalemia in this patient population. All 1,094 trial participants had diastolic blood pressure >95 mm Hg and GFR of 20 to 65 mL/min/1.73 m2.

During the initial double-blind phase, they were randomized to the beta blocker metoprolol succinate extended release (50-200 mg/day), the angiotensin-converting enzyme inhibitor (ACEI) ramipril (2.5-10.0 mg/d), or the calcium-channel blocker amlodipine besylate (5-10 mg/d). Their mean arterial blood pressure goals were either 102 to 107 mm Hg or <92 mm Hg.

The outcome variable of hyperkalemia was defined as potassium concentration >5.5 mEq/L at one of the follow-up visits at the Cleveland Clinic Foundation, or a hyperkalemia-related stop point established by another of the participating clinical centers. During the mean 3 years of follow-up, 6,497 potassium measurements were gathered.

The data showed that 80 events in 51 subjects met hyperkalemia criteria.

Of the patients with baseline GFR of 40 mL/min/1.73 m2 or less, 11.2% had a hyperkalemic event, versus <1.6% of subjects who had a baseline GFR of >40 mL/min/1.73 m2. Indeed, after multivariable adjustments, the risk of hyperkalemia was significantly lower in patients with average baseline GFR of >50 mL/min/1.73 m2 relative to those with GFRs of <=30 mL/min/1.73 m2 (P<.001) and 31 to 40 mL/min/1.73 m2 (P=.007).

A baseline BMI of <=25 kg/m2, relative to BMI of >25 to <=30 kg/m2, was associated with an increased risk for hyperkalemia in both univariate (P=.004) and multivariate analyses (P=.07).

The multivariable-adjusted odds of hyperkalemia also significantly increased among the patients who received ramipril as compared with metoprolol (hazard ratio [HR], 2.85; 95% CI, 1.50-5.42; P=.001) and amlodipine (HR, 7.00; 95% CI, 2.29-21.39; P<.001). Even with ACEI treatment, a GFR >40 mL/min/1.73m2 was still associated with a small hyperkalemia risk, the authors noted.

Other results showed that a higher ratio of urinary protein to urinary creatinine at baseline was linked to increased hyperkalemia risk in univariate analysis. However, in multivariate analysis, only patients with the greatest protein excretion showed significantly elevated risk.

During follow-up, a GFR <=40 mL/min/1.73 m2 (vs >50 mL/min/1.73 m2) and a potassium measurement of >=4 mEq/L (vs <4 mEq/L) were significant predictors of hyperkalemia risk. Finally, controlling for the most recent GFR showed that diuretic use reduced the probability of hyperkalemia by 59% (P=.006).

"Our study has important clinical implications," the researchers wrote. "If GFR at the time of initiation of therapy and during treatment is higher than 40 mL/min/1.73 m2, routine monitoring of serum potassium level is sufficient, even in those treated with ACEIs."

On the other hand, these results justify more frequent monitoring of serum potassium in certain patient subgroups, they added. (Weinberg JM, et al. Arch Intern Med 2009;169:1587-1594.)

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