Elevated serum aldosterone can be vasculotoxic and facilitates cardiorenal damage. Renin-angiotensin-aldosterone inhibitors (RAASi) reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia (HK). Patiromer, a nonabsorbed potassium binder, decreases serum potassium (K+) in CKD patients on RAASi. We examined the effect of patiromer on serum aldosterone levels, plasma renin activity (PRA), systolic (SBP) and diastolic blood pressure (DBP), and urinary albumin-to-creatinine ratio (UACR) in CKD patients on RAASi with HK (serum K+ 5.1–<6.5 mEq/L) in the phase 3 OPAL-HK study (4-week open-label patiromer treatment phase [N = 243]; 8-week placebo-controlled randomized withdrawal phase [N = 107]).Design and Method:
Assessments conducted at baseline (day 1), on day 3 of both study phases, and weekly until the end of the study included serum K+, SBP/DBP, serum creatinine, eGFR, aldosterone, and PRA. Urine samples were collected for ACR at baseline and every 4 weeks through study end.Results:
In the treatment phase, mean (standard error [SE]) serum K+ decreased concordantly with mean serum aldosterone (−1.99 [0.51] ng/dL, P = 0.0001), SBP/DBP (−5.64 [1.04] mmHg/−3.84 [0.69] mmHg, P < 0.0001 [Figure]), PRA (−0.44 [0.63] μg/L/hr; P = NS) and UACR (−203.7 [54.7] mg/g, P = 0.0003). In the withdrawal phase, mean aldosterone levels were sustained with patiromer (+0.23 [1.07] ng/dL; P = NS) and increased with placebo (+2.78 [1.25] ng/dL; P ≤ 0.03). Patients on patiromer had reductions in mean SBP/DBP (−6.70 [1.59] mmHg/−2.15 [1.06] mmHg, P ≤ 0.05) whereas those on placebo did not (−1.21 [1.89] mmHg/+1.72 [1.26] mmHg, P = NS). Significant changes in PRA were observed only in the placebo group (−3.90 [1.41] μg/L/hr; P = 0.0067). Patiromer was generally well tolerated, with mild-moderate constipation occurring in 11% (treatment phase) and 4% (randomized withdrawal phase). of patiromer-treated patients. AEs leading to discontinuation occurred in 6% and 2% of patiromer patients, respectively.Conclusions:
Patiromer reduced serum K+ and serum aldosterone levels independent of PRA in CKD patients with HK on RAASi.