New Insights into Effects of Dual RAAS Blockade in CKD

In patients with chronic kidney disease (CKD), the acute response to a potassium challenge may predict chronic changes in potassium level while receiving dual renin-angiotensin-aldosterone (RAAS) blockade, reports a study in Hypertension.

The randomized, crossover trial included 18 patients with hypertension and CKD with a glomerular filtration rate of 25 to 65 mL/min. In random order, the patients received four weeks of treatment with dual RAAS blockade, consisting of lisinopril 40 mg/dL and spironolactone 25 mg/dL, and four weeks of placebo. After each treatment, dynamic renal potassium excretion and serum potassium were assessed after a 35 mmol oral potassium challenge.

Ambulatory potassium concentrations were 4.87 mmol/L after four weeks on lisinopril/spironolactone versus 4.37 mmol/L after four weeks on placebo. After lisinopril/spironolactone treatment, a small 0.44 mmol/h drop in potassium excretion was accompanied by a 0.67 mmol/L increase in serum potassium, suggesting impairment of extrarenal/transcellular potassium disposition. The increase in serum potassium after potassium challenge was a significant predictor of the increase in ambulatory potassium on lisinopril/spironolactone.

Dual RAAS blockade can improve cardiovascular and renal outcomes in patients with hypertension. However, in patients with CKD, it can lead to hyperkalemia. In this trial, lisinopril/spironolactone increases serum potassium concentration not only through reduced potassium excretion, but also through impairment of extrarenal potassium disposition. Changes in dynamic potassium handling may become useful in predicting changes in ambulatory potassium concentration in response to this drug treatment strategy [Preston RA, Afshartous D, Garg D, Medrano S, Alonso AB, Rodriguez R: Mechanisms of impaired potassium handling with dual renin-angiotensin-aldosterone blockade in chronic kidney disease. Hypertension 2009; 53:754–760].