Does the temporary decrease in the estimated glomerular filtration rate (eGFR) after initiation of mineralocorticoid receptor (MR) antagonist treatment lead to a long-term renal protective effect?

• Published in: Hypertension research Vol. 42; no. 12; pp. 1841 - 1847
• Main Author: Sato, Atsuhisa
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-12-2019
• Subjects: Animals; Beta blockers; Glomerular Filtration Rate - drug effects; Health risk assessment; Heart failure; Humans; Hypertension; Hypertension - complications; Hypertension - drug therapy; Hypertension - physiopathology; Kidney diseases; Kidneys; Long term; Mineralocorticoid Receptor Antagonists - therapeutic use; Renal Insufficiency, Chronic - etiology; Renal Insufficiency, Chronic - physiopathology; Renal Insufficiency, Chronic - prevention & control; Chronic kidney disease; Aldosterone; Mineralocorticoid receptor antagonists; Renin-angiotensin system inhibitors; Sodium–glucose cotransporter 2 inhibitor
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1038/s41440-019-0320-9

Recently, deleterious effects of aldosterone on the kidney via mineralocorticoid receptors (MRs) have been noted. MR antagonists have been reported to show significant antialbuminuric effects when added to angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers. However, a decrease in the estimated glomerular filtration rate (eGFR) has been reported during MR antagonist treatment. On the other hand, although the eGFR often decreases, significant reductions in total mortality and cardiovascular events have been observed in large-scale clinical trials in patients with chronic heart failure. What are the implications of the changes in eGFR due to MR antagonist treatment? Glomerular hyperfiltration has been reported to occur with an aldosterone excess, and it can be seen that relative glomerular hyperfiltration is rapidly corrected with MR antagonism, even without aldosterone excess. This is reflected in the initial temporary decrease in the eGFR. After MR antagonist treatment, eGFR decreases temporarily, and it appears that renal function has deteriorated. However, if renal function has actually deteriorated, a reduction in all-cause and cardiovascular death is unlikely to occur in the clinical studies in patients with chronic heart failure. That is, the initial transient decrease in eGFR by the MR antagonist appears to work effectively to provide fine adjustment of glomerular pressure, and this approach works advantageously to suppress long-term cardiovascular events. It is expected that a number of long-term, large-scale clinical research trials targeting renal events and all-cause and cardiovascular death in CKD patients treated with an MR antagonist will be planned.