Increased serum potassium affects renal outcomes: a post hoc analysis of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial.
OBJECTIVE
To assess the effect of an angiotensin receptor blocker (ARB) on serum potassium and the effect of a serum potassium change on renal outcomes in patients with type 2 diabetes and nephropathy.


METHODS
We performed a post hoc analysis in patients with type 2 diabetes participating in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. Renal outcomes were defined as a composite of doubling of serum creatinine or end-stage renal disease.


RESULTS
At month 6, 259 (38.4%) and 73 (10.8%) patients in the losartan group and 151 (22.8%) and 34 (5.1%) patients in the placebo group had serum potassium ≥5.0 mmol/l and ≥5.5 mmol/l, (p < 0.001), respectively. Losartan was an independent predictor for serum potassium ≥5.0 mmol/l at month 6 (OR 2.8; 95% CI 2.0-3.9). Serum potassium at month 6 ≥ 5.0 mmol/l was in turn associated with increased risk for renal events (HR 1.22; 95% CI 1.00-1.50), independent of other risk factors. Adjustment of the overall treatment effects for serum potassium augmented losartan's renoprotective effect from 21% (6-34%) to 35% (20-48%), suggesting that the renoprotective effects of losartan are offset by its effect on serum potassium.


CONCLUSIONS
In this study, we found that treatment with the ARB losartan is associated with a high risk of increased serum potassium levels, which is in turn associated with an increased risk of renal outcomes in patients with diabetes and nephropathy. Whether additional management of high serum potassium would further increase the renal protective properties of losartan is an important clinical question.
Miao
Y
Y
Department of Clinical Pharmacology, University Medical Centre Groningen, the Netherlands.
Dobre
D
D
Heerspink
H J Lambers
HJ
Brenner
B M
BM
Cooper
M E
ME
Parving
H-H
HH
Shahinfar
S
S
Grobbee
D
D
de Zeeuw
D
D
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000503:physiopathology; D005260:Female; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood*
D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan; D011188:Potassium