Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis.
Hypertension 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.



We 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 Unpublished summary data were obtained from investigators.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.



Nineteen 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 m(2)). 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.



Mineralocorticoid receptor antagonism reduces blood pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit.
Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Center, 126 University Place, Glasgow, UK. gemma.currie@glasgow.ac.uk.
Gemma
0000-0002-0797-0224
G
Currie
Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Center, 126 University Place, Glasgow, UK.
Alison H M
AH
Taylor
Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Toshiro
T
Fujita
Department of Clinical Study and Informatics, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
Hiroshi
H
Ohtsu
Steno Diabetes Center, Niels Steensens Vej, Gentofte, Denmark.
Morten
M
Lindhardt
Steno Diabetes Center, Niels Steensens Vej, Gentofte, Denmark.|Health, Aarhus University, Aarhus, Denmark.|NNF Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Peter
P
Rossing
Department of Nephrology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Lene
L
Boesby
Departments of Cardiology and Nephrology, University Hospital Birmingham and School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
Nicola C
NC
Edwards
Departments of Cardiology and Nephrology, University Hospital Birmingham and School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
Charles J
CJ
Ferro
Departments of Cardiology and Nephrology, University Hospital Birmingham and School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
Jonathan N
JN
Townend
Department of Internal Medicine and Pharmacy, Erasmus MC, Rotterdam, The Netherlands.
Anton H
AH
van den Meiracker
VA Medical Center, 4100 West Third St, Dayton, OH, 45428, USA.
Mohammad G
MG
Saklayen
Metabolic Diseases Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
Sonia
S
Oveisi
Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Center, 126 University Place, Glasgow, UK.
Alan G
AG
Jardine
Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Center, 126 University Place, Glasgow, UK.
Christian
C
Delles
Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK.
David J
DJ
Preiss
Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Center, 126 University Place, Glasgow, UK.
Patrick B
PB
Mark
D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D018450:Disease Progression; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced*; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D010352:Patient Dropouts / Q000706:statistics & numerical data; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy*; D018570:Risk Assessment
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists