Determinants and changes associated with aldosterone breakthrough after angiotensin II receptor blockade in patients with type 2 diabetes with overt nephropathy.
OBJECTIVE
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.


METHODS
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.
Nephrology 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.
Olivier
O
Moranne
George
G
Bakris
Coraline
C
Fafin
Guillaume
G
Favre
Christian
C
Pradier
Vincent L M
VL
Esnault
D000368:Aged; D000450:Aldosterone / Q000097:blood*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012982:Sodium, Dietary / Q000008:administration & dosage
D057911:Angiotensin Receptor Antagonists; D012982:Sodium, Dietary; D000450:Aldosterone