Treatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors

Abstract

Elevated serum aldosterone can be vasculotoxic and facilitate cardiorenal damage. Renin-angiotensin system inhibitors reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia. Patiromer, a nonabsorbed potassium binder, decreases serum potassium in patients with chronic kidney disease on renin-angiotensin system inhibitors. Here we examined the effect of patiromer treatment on serum aldosterone, blood pressure, and albuminuria in patients with chronic kidney disease on renin-angiotensin system inhibitors with hyperkalemia (serum potassium 5.1-6.5 mEq/l). We analyzed data from the phase 3 OPAL-HK study (4-week initial treatment phase of 243 patients; 8-week randomized withdrawal phase of 107 patients). In the treatment phase, the (mean ± standard error) serum potassium was decreased concordantly with the serum aldosterone (-1.99 ± 0.51 ng/dl), systolic/diastolic blood pressure (-5.64 ± 1.04 mm Hg/-3.84 ± 0.69 mm Hg), and albumin-to-creatinine ratio (-203.7 ± 54.7 mg/g), all in a statistically significant manner. The change in the plasma renin activity (-0.44 ± 0.63 μg/l/hr) was not significant. In the withdrawal phase, mean aldosterone levels were sustained with patiromer (+0.23 ± 1.07 ng/dl) and significantly increased with placebo (+2.78 ± 1.25 ng/dl). Patients on patiromer had significant reductions in mean systolic/diastolic blood pressure (-6.70 ± 1.59/-2.15 ± 1.06 mm Hg), whereas those on placebo did not (-1.21 ± 1.89 mm Hg/+1.72 ± 1.26 mm Hg). Significant changes in plasma renin activity were found only in the placebo group (-3.90 ± 1.41 μg/l/hr). Thus, patiromer reduced serum potassium and aldosterone levels independent of plasma renin activity in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.

Electrolyte and Acid-Base Disorders in Chronic Kidney Disease and End-Stage Kidney Failure

“…The main adverse effects were mild-to-moderate constipation (11%) and mild hypomagnesaemia (3%). In addition to lowering K, patiromer treatment was associated with significant reduction in serum aldosterone and blood pressure [19]. Thus, patiromer may exert a long-term organ protective effect by reducing aldosterone level [20,21].…”

Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy

“…With the recent development of patiromer, a non-absorbed potassium binder, a safe option for the treatment of chronic hyperkalemia is available, maintaining and using RAAS inhibitors including spironolactone, in CKD and heart failure 41 . Patiromer has also been shown to decrease potassium and aldosterone levels in patients with CKD and hyperkalemia on RAAS inhibitors independent of renin activity 42 . The recent ARTS-DN (Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy) study demonstrated greater reduction in albuminuria with the addition of finerenone to ACEI or ARB in patients with diabetic nephropathy compared with placebo (see “Recent clinical trials” section for details) 43, 44 .…”

Patiromer: A Review in Hyperkalaemia

“…decreased levels) was maintained in patients who continued patiromer treatment for 8 more weeks, but aldosterone levels increased significantly (p B 0.03) in patients who switched to placebo. ACR benefits were also maintained with further patiromer therapy, while significant (p \ 0.05) reductions were observed in SBP and DBP [18].…”

“…4.2) [18]. In the initial treatment phase (n = 243), patiromer resulted in significant (p \ 0.001) decreases from baseline to week 4 in serum aldosterone, systolic blood pressure (SBP), diastolic blood pressure (DBP), and urine albumin:creatinine ratio (ACR), but not plasma renin activity.…”