ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. VAL-K Study Group

Kidney Int. 2000 Nov;58(5):2084-92. doi: 10.1111/j.1523-1755.2000.00381.x.


Background: Inhibition of the renin-angiotensin system is known to raise serum potassium [K(+)] levels in patients with renal insufficiency or diabetes. No study has evaluated the comparative effects of an angiotensin-converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum [K(+)] in people with renal insufficiency.

Methods: The study was a multicenter, randomized, double crossover design, with each period lasting one month. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasian) participated, with the mean age being 56 +/- 2 years. Mean baseline serum [K(+)] was 4.4 +/- 0.1 mEq/L. The glomerular filtration rate (GFR) was 65 +/- 5 mL/min/1.73 m(2), and blood pressure was 150 +/- 2/88 +/- 1 mm Hg. The main outcome measure was the difference from baseline in the level of serum [K+], plasma aldosterone, and GFR following the initial and crossover periods.

Results: For the total group, serum [K(+)] changes were not significantly different between the lisinopril or valsartan treatments. The subgroup with GFR values of < or = 60 mL/min/1.73 m(2) who received lisinopril demonstrated significant increases in serum [K(+)] of 0.28 mEq/L above the mean baseline of 4.6 mEq/L (P = 0.04). This increase in serum [K(+)] was also accompanied by a decrease in plasma aldosterone (P = 0.003). Relative to the total group, the change in serum [K(+)] from baseline to post-treatment in the lisinopril group was higher among those with GFR values of < or = 60 mL/min/1.73 m(2). The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum [K(+)], 0.12 mEq/L above baseline (P = 0.1), a 43% lower value when compared with the change in those who received lisinopril. This blunted rise in [K(+)] in people taking valsartan was not associated with a significant decrease in plasma aldosterone (P = 0.14).

Conclusions: In the presence of renal insufficiency, the ARB valsartan did not raise serum [K(+)] to the same degree as the ACE inhibitor lisinopril. This differential effect on serum [K(+)] is related to a relatively smaller reduction in plasma aldosterone by the ARB and is not related to changes in GFR. This study provides evidence that increases in serum [K(+)] are less likely with ARB therapy compared with ACE inhibitor therapy in people with renal insufficiency.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aldosterone / blood
  • Angiotensin Receptor Antagonists*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Cross-Over Studies
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Kidney / physiopathology
  • Lisinopril / therapeutic use*
  • Male
  • Middle Aged
  • Potassium / blood*
  • Renal Insufficiency / blood*
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency / physiopathology
  • Tetrazoles / therapeutic use*
  • Valine / analogs & derivatives*
  • Valine / therapeutic use*
  • Valsartan


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Tetrazoles
  • Aldosterone
  • Valsartan
  • Lisinopril
  • Valine
  • Potassium