Aldosterone blockade in chronic kidney disease: can it improve outcome?
OBJECTIVE
The purpose of this review is to explain the rationale and limitations for use of mineralocorticoid receptor blockers (MRBs) for the treatment of chronic kidney disease (CKD) and its complications.


RESULTS
Recent studies in animal models of CKD demonstrate that blockade of the mineralocorticoid receptor using spironolactone or eplerenone decreases inflammation, oxidative stress, proteinuria and glomerular and tubular injury. Patients with CKD are at very high risk for progression of kidney disease and major cardiovascular events. Recent studies in patients with CKD demonstrate that administration of low doses of MRBs added onto an angiotensin-converting enzyme inhibitor-based regimen reduces proteinuria--a risk marker for both progressive kidney disease and cardiovascular events. However, incident hyperkalemia, an unwanted side effect, dampened enthusiasm for this approach. There are no large-scale, long-term outcome trials examining whether MRB can slow progression of kidney disease or prevent cardiovascular events.


CONCLUSIONS
At this time it is unknown whether mineralocorticoid receptor blockade can improve outcomes in patients with CKD. To move this field forward and determine whether these agents can improve the lives of patients with kidney disease, novel strategies to prevent or ameliorate hyperkalemia are needed.
Toto
Robert D
RD
The University of Texas Southwestern Medical Center Dallas, Dallas, Texas 5323, USA. robert.toto@utsouthwestern.edu
D000450:Aldosterone / Q000502:physiology; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D006801:Humans; D006947:Hyperkalemia / Q000209:etiology; D047908:Intracellular Signaling Peptides and Proteins; D007674:Kidney Diseases / Q000188:drug therapy*; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D015778:Minor Histocompatibility Antigens; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011507:Proteinuria / Q000188:drug therapy; D012964:Sodium / Q000378:metabolism; D000076204:WNK Lysine-Deficient Protein Kinase 1
D047908:Intracellular Signaling Peptides and Proteins; D000451:Mineralocorticoid Receptor Antagonists; D015778:Minor Histocompatibility Antigens; D000450:Aldosterone; D012964:Sodium; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human