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Determinants and changes associated with aldosterone breakthrough after angiotensin II receptor blockade in patients
Olivier Moranne1, George Bakris, Coraline Fafin
1Nephrology and, †Epidemiology Departments, Nice University Hospital, Nice, France;, ‡ASH Comprehensive Hypertension Center, University of Chicago, Chicago, Illinois, §Institut National de la Santé et de la Recherche Médicale U1081, Nice Sophia-Antipolis University, Nice, France.
Background And Objectives:
Inhibition of the renin-angiotensin-aldosterone system decreases proteinuria and slows estimated GFR decline in patients with type 2 diabetes mellitus with overt nephropathy. Serum aldosterone levels may increase during renin-angiotensin-aldosterone system blockade. The determinants and consequences of this aldosterone breakthrough remain unknown.
Design, Setting, Participants, & Measurements:
This study examined the incidence, determinants, and changes associated with aldosterone breakthrough in a posthoc analysis of a randomized study that compared the effect of two angiotensin II receptor blockers in patients with type 2 diabetes mellitus with overt nephropathy.
Results:
Of 567 of 860 participants included in this posthoc analysis, 28% of participants developed aldosterone breakthrough, which was defined by an increase greater than 10% over baseline values of serum aldosterone levels after 1 year of angiotensin II receptor blocker treatment. Factors independently associated with aldosterone breakthrough at 1 year were lower serum aldosterone and potassium levels at baseline, higher decreases in sodium intake, systolic BP, and estimated GFR from baseline to 1 year, and use of losartan versus telmisartan. Aldosterone breakthrough at 6 months was not sustained at 1 year in 69% of cases, and it did not predict estimated GFR decrease and proteinuria increase between 6 months and 1 year.
Conclusions:
Aldosterone breakthrough is a frequent event 1 year after initiating renin-angiotensin-aldosterone system blockade, particularly in participants exposed to intensive lowering of BP with sodium depletion and short-acting angiotensin II receptor blockers. Short-term serum aldosterone level increases at 6 months are not associated with negative kidney outcomes between 6 months and 1 year.
Insights
Aldosterone breakthrough, an increase in aldosterone during renin-angiotensin-aldosterone system blockade, is common in type 2 diabetes patients. This event at 6 months did not predict long-term kidney decline.
Area of Science:
- Nephrology
- Endocrinology
- Cardiovascular Medicine
Background:
- Renin-angiotensin-aldosterone system (RAAS) inhibition benefits diabetic nephropathy but can increase aldosterone.
- Aldosterone breakthrough (AB) is a known phenomenon, but its triggers and clinical significance are unclear.
- Understanding AB is crucial for optimizing RAAS blockade in type 2 diabetes mellitus (T2DM).
Purpose of the Study:
- To investigate the incidence, determinants, and consequences of aldosterone breakthrough in T2DM patients with nephropathy.
- To analyze factors associated with AB development during RAAS blockade.
- To assess the relationship between AB and kidney function decline.
Main Methods:
- Posthoc analysis of a randomized controlled trial comparing two angiotensin II receptor blockers (ARBs) in T2DM patients.
- Inclusion of 567 patients with overt nephropathy.
- Definition of AB as >10% increase in serum aldosterone from baseline after 1 year of ARB treatment.
Main Results:
- Aldosterone breakthrough occurred in 28% of patients after 1 year of ARB treatment.
- Independent predictors of AB included lower baseline aldosterone/potassium, greater BP/eGFR reduction, and losartan use.
- AB at 6 months was transient in 69% and did not predict kidney function decline or proteinuria increase between 6 months and 1 year.
Conclusions:
- Aldosterone breakthrough is a frequent occurrence during RAAS blockade in T2DM patients with nephropathy.
- Intensive blood pressure lowering with sodium depletion and short-acting ARBs are associated with higher AB incidence.
- Transient 6-month aldosterone increases do not appear to negatively impact kidney outcomes in the subsequent year.
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