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      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

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          Abstract

          Aims/hypothesis

          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/interpretation

          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.

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          Most cited references23

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          The frequency of hyperkalemia and its significance in chronic kidney disease.

          Hyperkalemia is a potential threat to patient safety in chronic kidney disease (CKD). This study determined the incidence of hyperkalemia in CKD and whether it is associated with excess mortality. This retrospective analysis of a national cohort comprised 2 103 422 records from 245 808 veterans with at least 1 hospitalization and at least 1 inpatient or outpatient serum potassium record during the fiscal year 2005. Chronic kidney disease and treatment with angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers (blockers of the renin-angiotensin-aldosterone system [RAAS]) were the key predictors of hyperkalemia. Death within 1 day of a hyperkalemic event was the principal outcome. Of the 66 259 hyperkalemic events (3.2% of records), more occurred as inpatient events (n = 34 937 [52.7%]) than as outpatient events (n = 31 322 [47.3%]). The adjusted rate of hyperkalemia was higher in patients with CKD than in those without CKD among individuals treated with RAAS blockers (7.67 vs 2.30 per 100 patient-months; P or=5.5 and or=6.0 mEq/L) hyperkalemic event was highest with no CKD (OR, 10.32 and 31.64, respectively) vs stage 3 (OR, 5.35 and 19.52, respectively), stage 4 (OR, 5.73 and 11.56, respectively), or stage 5 (OR, 2.31 and 8.02, respectively) CKD, with all P < .001 vs normokalemia and no CKD. The risk of hyperkalemia is increased with CKD, and its occurrence increases the odds of mortality within 1 day of the event. These findings underscore the importance of this metabolic disturbance as a threat to patient safety in CKD.
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            Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values.

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              Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system.

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                Author and article information

                Contributors
                h.j.lambers.heerspink@med.umcg.nl
                Journal
                Diabetologia
                Diabetologia
                Springer-Verlag (Berlin/Heidelberg )
                0012-186X
                1432-0428
                30 September 2010
                30 September 2010
                January 2011
                : 54
                : 1
                : 44-50
                Affiliations
                [1 ]Department of Clinical Pharmacology, University Medical Centre Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands
                [2 ]Brigham and Women’s Hospital and Harvard School of Medicine, Boston, MA USA
                [3 ]Baker IDI Heart and Diabetes Research Institute, Melbourne, VIC Australia
                [4 ]Department of Medical Endocrinology, University Hospital of Copenhagen, Copenhagen, Denmark
                [5 ]The Faculty of Health Science, Aarhus University, Aarhus, Denmark
                [6 ]Shahinfar Consulting, The Children’s Hospital of Philadelphia, Philadelphia, PA USA
                [7 ]Julius Center for Health Science and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
                Article
                1922
                10.1007/s00125-010-1922-6
                2995871
                20882268
                ab237986-b490-41b3-99df-2eade6a18a89
                © The Author(s) 2010
                History
                : 24 June 2010
                : 1 September 2010
                Categories
                Article
                Custom metadata
                © Springer-Verlag 2011

                Endocrinology & Diabetes
                potassium,type 2 diabetes,angiotensin receptor blocker,nephropathy,losartan

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