EFFICACY OF THE ANGIOTENSIN RECEPTOR BLOCKER LOSARTAN DURING HIGH POTASSIUM INTAKE IN CKD PATIENTS

Abstract

Objective: High potassium intake increases natriuresis and lowers blood pressure (BP). Whether these beneficial effects are also present in chronic kidney disease (CKD) patients and whether potassium intake affects BP and proteinuria-lowering efficacy of angiotensin receptor blockade (ARB) is unknown. We set out to address the effect of potassium intake on BP and proteinuria response to losartan in non-diabetic proteinuric CKD patients. Design and method: We performed a post-hoc analysis of a placebo-controlled interventional cross-over study in which 33 non-diabetic proteinuric patients (mean baseline proteinuria 3.8 g/d) were treated for 6 weeks with placebo, losartan 100 mg, and losartan/hydrochlorothiazide 100 mg/25 mg, respectively. Patients underwent the 3 interventions during both a high (>200 mmol/d) and low-sodium diet (<100 mmol/d), in randomized order. To analyze the effects potassium intake, we categorized patients based on median split of 24-hour urinary potassium excretion, reflecting potassium intake. Treatment responses relative to placebo during high sodium were assessed. We used repeated measurements ANOVA with potassium intake as between subjects factor. Results: Mean potassium intake was stable during all 6 treatment periods. Patients with high potassium intake (>85 mmol/day) had similar BP reductions across all treatments as compared to low potassium intake (<85 mmol/day), whereas a trend of lower proteinuria reduction (p = 0.052) was observed for all treatments. Proteinuria reduction to losartan monotherapy was significantly lower during high potassium intake (20% vs. 40%, p = 0.02). The differences in antiproteinuric response abolished when adding a low sodium diet, hydrochlorothiazide, or both to losartan. Serum potassium was similar in both potassium intake groups throughout the study. Conclusions: In proteinuric CKD patients, the proteinuria, but not BP-lowering response to losartan was hampered during high potassium intake. Differences disappeared after sodium status change by low sodium diet and/or hydrochlorothiazide, suggesting that ARB inhibits natriuresis during high potassium intake, via a yet unknown mechanism.