Abstract
BackgroundHypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease.MethodsWe conducted a meta-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966–2014), EMBASE (1947–2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators. We included randomised controlled trials, and the first period of randomised cross over trials lasting ≥4 weeks in adults.ResultsNineteen trials (21 study groups, 1 646 patients) were included. In random effects meta-analysis, addition of mineralocorticoid receptor antagonists to renin angiotensin system inhibition resulted in a reduction from baseline in systolic blood pressure (−5.7 [−9.0, −2.3] mmHg), diastolic blood pressure (−1.7 [−3.4, −0.1] mmHg) and glomerular filtration rate (−3.2 [−5.4, −1.0] mL/min/1.73 m2). Mineralocorticoid receptor antagonism reduced weighted mean protein/albumin excretion by 38.7 % but with a threefold higher relative risk of withdrawing from the trial due to hyperkalaemia (3.21, [1.19, 8.71]). Death, cardiovascular events and hard renal end points were not reported in sufficient numbers to analyse.ConclusionsMineralocorticoid receptor antagonism reduces blood pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0337-0) contains supplementary material, which is available to authorized users.
Highlights
Hypertension and proteinuria are critically involved in the progression of chronic kidney disease
The beneficial effects on outcomes were confounded by increased risk of hyperkalaemia, a factor limiting mineralocorticoid receptor antagonists (MRA) prescribing in Chronic kidney disease (CKD) [17,18,19]
Similar findings were described in a more recent metaanalysis on the cardiovascular actions of MRAs in CKD [20]. The conclusions of these analyses are drawn from mainly published proteinuria data only, derived by consolidating disparate urinary protein excretion measures used in different trials
Summary
Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Aldosterone excess is a risk factor for progression of kidney disease. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease. Hypertension (HTN) is the major modifiable risk factor for CKD progression and is associated with development of left ventricular hypertrophy (LVH) and proteinuria, both predictors of CV mortality [3, 7]. There is renewed interest in aldosterone as a mediator of CV and renal disease, beyond its BP effect resulting in an enthusiasm for using mineralocorticoid receptor antagonists (MRA) to minimised proteinuria and delay CKD progression. The beneficial effects on outcomes were confounded by increased risk of hyperkalaemia, a factor limiting MRA prescribing in CKD [17,18,19]. In some studies in these meta-analyses, the MRA effect is impossible to dissociate from that of additional antihypertensives co-administered with MRA in the intervention arm
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
