Department of Internal Medicine, Division of Nephrology and Hypertension, International University of Health and Welfare Mita Hospital, Tokyo, Japan.
Hypertens Res. 2019 Dec;42(12):1841-1847. doi: 10.1038/s41440-019-0320-9. Epub 2019 Sep 6.
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.
最近，人们注意到醛固酮通过盐皮质激素受体（MR）对肾脏产生有害影响。据报道，当 MR 拮抗剂与血管紧张素转换酶抑制剂或血管紧张素 II 型 1 型受体阻滞剂联合使用时，可显著减少白蛋白尿。然而，在使用 MR 拮抗剂治疗期间，已报道估算肾小球滤过率（eGFR）下降。另一方面，尽管 eGFR 经常下降，但在慢性心力衰竭患者的大规模临床试验中，观察到总死亡率和心血管事件的显著降低。MR 拮抗剂治疗引起的 eGFR 变化有何影响？醛固酮过多会导致肾小球高滤过，并且可以看到，即使没有醛固酮过多，MR 拮抗作用也可以迅速纠正相对肾小球高滤过。这反映在 eGFR 的初始短暂下降中。在 MR 拮抗剂治疗后，eGFR 暂时下降，肾功能似乎恶化。然而，如果肾功能确实恶化，在慢性心力衰竭患者的临床研究中，不太可能发生全因和心血管死亡的减少。也就是说，MR 拮抗剂引起的 eGFR 初始短暂下降似乎有效地发挥作用，提供了肾小球压力的精细调节，这种方法有利于抑制长期心血管事件。预计将计划针对接受 MR 拮抗剂治疗的 CKD 患者的肾脏事件和全因及心血管死亡的多项长期、大规模临床研究试验。
