OS 19-03 TREATMENT WITH PATIROMER RESULTED IN DECREASES IN ALDOSTERONE IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND HYPERKALEMIA ON RAAS INHIBITORS: RESULTS FROM OPAL-HK.

OBJECTIVE: 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.