Diminished antiproteinuric effect of the angiotensin receptor blocker losartan during high potassium intake in patients with CKD

Abstract

Background: Angiotensin II type 1 receptor blockers (ARBs) lower blood pressure (BP) and proteinuria and reduce renal disease progression in many-but not all-patients. Reduction of dietary sodium intake improves these effects of ARBs. Dietary potassium intake affects BP and proteinuria. We set out to address the effect of potassium intake on BP and proteinuria response to losartan in non-diabetic proteinuric chronic kidney disease (CKD) patients.

Methods: We performed a post hoc analysis of a placebo-controlled interventional cross-over study in 33 non-diabetic proteinuric patients (baseline mean arterial pressure and proteinuria: 105 mmHg and 3.8 g/day, respectively). Patients were treated for 6 weeks with placebo, losartan and losartan/hydrochlorothiazide (HCT), combined with a habitual (∼200 mmol/day) and low-sodium (LS) diet (<100 mmol/day), in randomized order. To analyse the effects of potassium intake, we categorized patients based on median split of 24-h urinary potassium excretion, reflecting potassium intake.

Results: Mean potassium intake was stable during all six treatment periods. Losartan and losartan/HCT lowered BP and proteinuria in all treatment groups. Patients with high potassium intake showed no difference in the BP effects compared with patients with low potassium intake. The antiproteinuric response to losartan monotherapy and losartan combined with HCT during the habitual sodium diet was significantly diminished in patients with high potassium intake (20% versus 41%, P = 0.011; and 48% versus 64%, P = 0.036). These differences in antiproteinuric response abolished when shifting to the LS diet.

Conclusions: In proteinuric CKD patients, the proteinuria, but not BP-lowering response to losartan during a habitual high-sodium diet was hampered during high potassium intake. Differences disappeared after sodium status change by LS diet.

Keywords: RAAS inhibition; blood pressure; chronic kidney disease; potassium intake; proteinuria.

FIGURE 1:

Study design. After inclusion patients were treated for 6 weeks with placebo, losartan (100 mg/day) and losartan plus HCT (losartan 100 mg/day plus HCT 25 mg/day). Patients underwent the three interventions during both an HS diet (∼200 mmol/day) and an LS diet (<100 mmol/day). The order of the drug intervention, as well as the sodium diet, was determined by randomization. R, randomization.

FIGURE 2:

The relative antiproteinuric and BP response to losartan with and without HCT during a HS diet and placebo during LS diet. (A) The antiproteinuric response to losartan monotherapy was significantly higher in patients with a low potassium intake compared with patients with a high potassium intake (P = 0.011). (B) This difference became smaller, but was still significant after adding HCT (P = 0.036). (C) Also, the antiproteinuric response to placebo during an LS diet was significantly higher in patients with a low potassium intake compared with patients with a high potassium intake (P = 0.032). No significant differences in BP response were observed between a high and low potassium intake. Values are mean ± SEM.