Predictors of Hyperkalemia Risk following Hypertension Control with Aldosterone Blockade

Abstract

Background: Aldosterone antagonists have proven efficacy for management of resistant hypertension and proteinuria reduction; however, they are not widely used due to risk of hyperkalemia. This study assesses the risk factors for hyperkalemia in patients with chronic kidney disease (CKD) and resistant hypertension whose blood pressure (BP) is reduced to a guideline goal. Methods: This is a two-center study conducted in university-based hypertension clinics directed by clinical hypertension specialists. Forty-six patients with resistant hypertension and stages 2 or 3 CKD (mean estimated glomerular filtration rate (eGFR) 56.5 ± 16.2 ml/min/1.73 m²) were evaluated for safety and efficacy of aldosterone blockade added to preexisting BP-lowering regimens. All patients were on three mechanistically complementary antihypertensive agents including a diuretic and a renin-angiotensin system blocker. Patients were evaluated after a median of 45 treatment days. The primary endpoint was change in systolic BP. Secondary endpoints included change in serum potassium, creatinine, eGFR, diastolic BP and tolerability. Results: The mean age of the patients studied was 64.9 ± 10.7 years, all were obese and 86% had type 2 diabetes, with 82% being African-American. Addition of aldosterone antagonism yielded a further mean reduction in systolic BP of 14.7 ± 5.1 mm Hg (p = 0.001). Females with BMI >30 and those with a baseline systolic BP >160 mm Hg were more likely to have a greater BP reduction to aldosterone antagonism. In total, 39% of the patients had a >30% decrease in eGFR when the BP goal was achieved. The mean increase in serum potassium was 0.4 mEq/l above baseline (p = 0.001), with 17.3% manifesting hyperkalemia, i.e. serum potassium >5.5 mEq/l. Predictors of hyperkalemia included a baseline eGFR of ≤45 ml/min/1.73 m² in whom serum potassium was >4.5 mEq/l on appropriately dosed diuretics. Contributing risks in this subgroup included a systolic BP reduction of >15 mm Hg associated with an eGFR fall of >30%. Conclusion: Aldosterone antagonism is effective and safe for achieving a BP goal among people with diabetic nephropathy when added to a triple antihypertensive regimen that includes a blocker of the renin-angiotensin system and an appropriately selected and dosed diuretic. Caution is advised when using aldosterone blockade for BP control in people with advanced stage 3 nephropathy with a serum potassium of >4.5 mEq/l for safety reasons.

Potassium Handling with Dual Renin-Angiotensin System Inhibition in Diabetic Nephropathy

“…Baseline serum potassium, urine potassium, and creatinine clearance predicted hyperkalemia independent of treatment group. A prior study specifically identified baseline serum potassium.4.5 mEq/L and estimated GFR,45 ml/min per 1.73 m 2 as hyperkalemia predictors (.5.5 mEq/L) in CKD stages 2 and 3 patients receiving spironolactone and another RAAS-inhibiting drug (32). This serum potassium was predictive of hyperkalemia (.6.0 mEq/L), and this GFR was a nonsignificant predictor in our study.…”

Mineralocorticoid Receptor Antagonist for Renal Protection

“…42 Recently, it was shown that several factors are associated with a significantly higher risk of incident hyperkalemia after initiation of MR antagonist, including baseline eGFR 45 mL/ min/1.73 m 2 , reduction in SBP > 15 mmHg, and decline in eGFR > 30%. 46 These patients should be closely monitored and dose adjustment or cessation of therapy should be considered if necessary.…”

Aldosterone

“…A recent study demonstrated that the predictors of hyperkalemia (i.e., serum potassium Ͼ5.5 mEq/L) in patients who had diabetic nephropathy, were on acceptable dosages of a diuretic and a renin-angiotensin blocker, and were treated with a mineralocorticoid antagonist had a baseline serum potassium level Ն4.5 Eq/L and a GFR Յof 45 ml/min per 1.73 m 2 (39).…”