Aldosterone breakthrough during aliskiren, valsartan, and combination (aliskiren + valsartan) therapy

Bomback, Andrew S.; Rekhtman, Yelena; Klemmer, Philip J.; Canetta, Pietro A.; Appel, Gerald B.

doi:10.1016/j.jash.2012.07.003

Cited by 33 publications

(21 citation statements)

References 27 publications

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“…It is unlikely that the observed reduction in serum aldosterone occurred by chance and was unrelated to patiromer's effect on sK. Decreases in the magnitude that we observed are unlikely to occur spontaneously in patients with kidney disease, 29,30 suggesting that the observed effect on aldosterone was driven by patiromer treatment. The effect of patiromer on aldosterone is further supported by the findings that subjects switched to placebo in the randomized withdrawal phase had increases in aldosterone, whereas those who continued patiromer therapy maintained the decreased aldosterone levels achieved in the initial treatment phase.…”

Section: Discussionmentioning

confidence: 69%

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

Weir

Bakris

Gross³

et al. 2016

Kidney International

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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.

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Section: Discussionmentioning

confidence: 69%

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

Weir

Bakris

Gross³

et al. 2016

Kidney International

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“…Although blockade of the RAAS has traditionally been performed with ACE inhibitors or ARBs, and more recently direct renin inhibitors have been tried [4] , 30-50% of patients on long-term therapy have unexpected elevations of serum aldosterone levels, a phenomenon termed 'aldosterone breakthrough' [4][5][6][7] . This paradoxical elevation in aldosterone levels in some ways mirrors animal studies in which aldosterone is infused over the background of ACE inhibitors or ARBs.…”

Section: Introductionmentioning

confidence: 99%

“…The phenomenon of aldosterone breakthrough, well described in the cardiac and renal literature [4,7,8,12] , may explain the mortality benefit of aldosterone blockade as add-on therapy to ACE inhibitors or ARBs in congestive heart failure (CHF) [13][14][15] . Following myocardial infarction, patients in the highest quartile of aldosterone levels have double the event rate of death, resuscitated cardiac arrest, recurrent or extended myocardial infarction, recurrent ischemia, CHF, and stroke [16] .…”

Section: Introductionmentioning

confidence: 99%

Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease: Efficacy and Safety

Bomback¹

2016

Blood Purif

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Mineralocorticoid receptor antagonists (MRAs) that block aldosterone's effects on both epithelial and non-epithelial receptors have become a mainstay of therapy for chronic heart failure. Given that cardiovascular events remain the leading cause of death for patients with end-stage renal disease (ESRD), the question of whether these MRAs can be employed in dialysis patients arises. This review summarizes the rationale for blocking aldosterone in patients with chronic and end-stage kidney disease and surveys the data on both the efficacy and safety of using MRAs in the ESRD population. A small but growing body of literature suggests that use of MRAs by ESRD patients is associated with lower blood pressure, reduced left ventricular (LV) mass, and improved LV ejection fraction. Recently, a large randomized trial found an overall 3-year mortality rate of 6.4% in ESRD patients on spironolactone 25 mg daily vs. 19.7% in ESRD patients on no MRA therapy (p = 0.002), without a significantly increased risk of hyperkalemia.

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“…Fundamentally, nullifying the effect of aldosterone effect on BP with an ARA would be expected to further reduce BP beyond what would be seen with any of these classes given alone or together. Such BP reduction relates to an ARA effect on aldosterone/volume, which would not be mechanistically redundant as is the case when an ACE inhibitor is added to an ARB or a DRI [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Dual Inhibitors: RAAS Blockers/Combination Therapies: What Do All These Trials Mean?

Sica

2014

Chronic Kidney Disease and Hypertension

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Aldosterone breakthrough during aliskiren, valsartan, and combination (aliskiren + valsartan) therapy

Cited by 33 publications

References 27 publications

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

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

Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease: Efficacy and Safety

Dual Inhibitors: RAAS Blockers/Combination Therapies: What Do All These Trials Mean?

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