Effect of Eplerenone on the Glomerular Filtration Rate (GFR) in Primary Aldosteronism: Sequential Changes in the GFR During Preoperative Eplerenone Treatment to Subsequent Adrenalectomy

Nakano, Yujiro; Yoshimoto, Takanobu; Fukuda, Tatsuya; Murakami, Masanori; Bouchi, Ryotaro; Minami, Isao; Hashimoto, Kazuhito; Fujii, Yasuhisa; Kihara, Kazunori; Ogawa, Yoshihiro

doi:10.2169/internalmedicine.0438-17

Cited by 10 publications

(12 citation statements)

References 26 publications

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“…In patients with PA, renal glomerular hyperfiltration is present due to an excess of aldosterone, which causes elevation of eGFR. These elevations appear to be reduced by treatment with an MR blocker due to improved glomerular hypertension [ 36 , 37 ]. In our study, the extent of reductions in eGFR during treatment of PA with esaxerenone was similar to that seen with other MR blockers, indicating that correction of hyperfiltration probably contributed to the observed reduction in eGFR, which may indicate recovery of the tubuloglomerular feedback damaged by hyperaldosteronism [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of esaxerenone (CS-3150), a newly available nonsteroidal mineralocorticoid receptor blocker, in hypertensive patients with primary aldosteronism

et al. 2020

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Mineralocorticoid receptor (MR) blockers are very beneficial for patients with hypertension and primary aldosteronism (PA). We investigated the efficacy and safety of a newly available nonsteroidal MR blocker, esaxerenone, in Japanese patients with hypertension and PA. A multicenter, open-label study was conducted in Japan between October 2016 and July 2017. Patients with hypertension and PA received 12 weeks of treatment with esaxerenone, initiated at 2.5 mg/day and escalated to 5 mg/day during week 2 or 4 of treatment, based on individual response. The only other permitted antihypertensive therapies were stable dosages of a Ca2+ channel blocker or α-blocker. The primary efficacy outcome was a change in sitting systolic and diastolic blood pressure (SBP/DBP) from baseline to the end of treatment. Forty-four patients were included; dose escalation to 5 mg/day was implemented for 41 of these patients. Significant decreases in SBP and DBP were observed (point estimates [95% confidence interval] −17.7 [−20.6, −14.7] and −9.5 [−11.7, −7.3] mmHg, respectively; both p < 0.0001 at the end of treatment). Significant BP reductions were evident from week 2 and continued through to week 8; BP remained stable until week 12. The antihypertensive effect of esaxerenone on SBP was significantly greater in females and in patients receiving monotherapy. The major drug-related adverse events were serum K+ increase and estimated glomerular filtration rate decrease (both 4.5%, n = 2); no gynecomastia or breast pain was observed. We conclude that esaxerenone is a potent MR blocker with favorable efficacy and safety profiles in patients with hypertension and PA.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of esaxerenone (CS-3150), a newly available nonsteroidal mineralocorticoid receptor blocker, in hypertensive patients with primary aldosteronism

et al. 2020

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“…have noted that PA patients experienced a reduction in eGFR after taking a high-dose MR antagonist (which reflects improvement of glomerular hyperfiltration after treatment), but 82% of them experienced a further reduction in eGFR after surgical adrenalectomy. 33 This suggests that even a high-dose MR antagonist treatment may not adequately suppress MR activation within the kidneys, and that further improvement in glomerular hyperfiltration 33 may be possible via surgery. Hundemer et al.…”

Section: Discussionmentioning

confidence: 99%

“…Nakano et al have noted that PA patients experienced a reduction in eGFR after taking a high-dose MR antagonist (which reflects improvement of glomerular hyperfiltration after treatment), but 82% of them experienced a further reduction in eGFR after surgical adrenalectomy. 33 This suggests that even a high-dose MR antagonist treatment may not adequately suppress MR activation within the kidneys, and that further improvement in glomerular hyperfiltration 33 may be possible via surgery. Hundemer et al reported that surgical treatment was associated with a lower risk of kidney dysfunction compared to MR antagonist treatment among patients with PA. 8,9 In the current study, reduction in eGFR after treatment was greater in the surgical treatment group than among those in the MR antagonist treatment group.…”

Section: Sensitivity Analysesmentioning

confidence: 99%

Associations Between Changes in Plasma Renin Activity and Aldosterone Concentrations and Changes in Kidney Function After Treatment for Primary Aldosteronism

Kobayashi

Haze

Yano

et al. 2020

Kidney International Reports

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Introduction: Greater reduction in estimated glomerular filtration rate (eGFR) after specific treatment for primary aldosteronism (PA) reflects improvement in glomerular hyperfiltration associated with PA and leads to better patient outcomes. However, little is known regarding the mechanisms underlying eGFR reduction after treatment for PA. Methods: We analyzed data from the nationwide PA registry in Japan. Patients were assigned to adrenalectomy (n ¼ 438) and mineralocorticoid receptor (MR) antagonist (n ¼ 746) groups. We assessed associations between changes in blood pressure (BP), plasma renin activity (PRA) and plasma aldosterone concentrations (PAC), and eGFR before and 6 months after treatment for both groups. Results: In a multivariable linear regression, the adjusted b values (95% confidence interval [CI]) for change in eGFR after treatment were À2.76 (À4.29, À1.22) ml/min per 1.73 m 2 for PRA (per 3.2 ng/ml per hour), and 1.97 (1.08, 2.85) ml/min per 1.73 m 2 for PAC (per 236.1 pg/ml) in the adrenalectomy group; and À0.45 (À0.89, À0.01) ml/min per 1.73 m 2 for PRA and À0.72 (À1.62, 0.18) ml/min per 1.73 m 2 for PAC in the MR antagonist group. Change in mean arterial pressure after treatment was not significantly associated with change in eGFR in either group. Changes in PRA and PAC but not BP before and 6 months after treatment for PA were associated with greater reductions in eGFR. Conclusion: Post-treatment improvements in glomerular hyperfiltration may be attributable to decreased MR activity in the kidneys, but not to reductions in systemic BP.

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“…A series of clinical studies have shown that renal hemodynamic alteration due to hyperaldosteronism results in glomerular hyperfiltration, 5,6 which is a cause of chronic renal injury 7 . The glomerular filtration rate (GFR) in PA rapidly decreases after the removal of aldosterone excess by ADX 5,8–10 or the blockade of aldosterone action by MRA 11 . To prevent renal injury in the long term, complete removal of glomerular hyperfiltration by ADX or a sufficient dose of MRA is recommended for patients with PA 11 .…”

Section: Introductionmentioning

confidence: 99%

Long‐term effects of primary aldosteronism treatment on patients with primary aldosteronism and chronic kidney disease

Nakano

Murakami

Hara

et al. 2022

Clinical Endocrinology

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Objective Primary aldosteronism (PA) is a major cause of secondary hypertension and is associated with chronic renal injury. The glomerular filtration rate (GFR) in PA rapidly decreases after the removal of glomerular hyperfiltration due to aldosterone excess by adrenalectomy (ADX) or mineralocorticoid receptor antagonist (MRA) treatment and is stable in the long term. However, the effects of these treatments on the long‐term renal function of PA patients with chronic kidney disease (CKD) is not well understood. Design and Patients In this single‐center, retrospective study, acute and chronic changes in the estimated GFR (eGFR) were examined in 107 patients with PA, including 49 patients with post‐treatment CKD　defined as eGFR < 60 ml/min/1.73 m2. Results The reduction in eGFR observed 1 month after ADX in the CKD group (N = 31) was −20.1 ± 8.2 ml/min/1.73 m2. Multivariate analysis showed that pre‐treatment eGFR and plasma aldosterone concentration were independent predictive factors of the acute reduction in eGFR after ADX. The reduction of eGFR observed 1 month after MRA administration in the post‐treatment CKD group (N = 18) was −9.2 ± 5.9 ml/min/1.73 m2. Multivariate analysis showed that the duration of hypertension and pre‐treatment eGFR were independent predictive factors of the acute reduction in eGFR after ADX administration. In 20 patients with CKD (N = 12 ADX and N = 8 MRA) followed for more than 5 years post‐treatment, there was no further significant decline in eGFR over a follow‐up period of 7 (6, 8) years nor any difference between the two treatment modalities. Conclusions Our study suggests that treatment of PA in stage 3 CKD is safe and useful in preventing renal injury.

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Effect of Eplerenone on the Glomerular Filtration Rate (GFR) in Primary Aldosteronism: Sequential Changes in the GFR During Preoperative Eplerenone Treatment to Subsequent Adrenalectomy

Cited by 10 publications

References 26 publications

Efficacy and safety of esaxerenone (CS-3150), a newly available nonsteroidal mineralocorticoid receptor blocker, in hypertensive patients with primary aldosteronism

Efficacy and safety of esaxerenone (CS-3150), a newly available nonsteroidal mineralocorticoid receptor blocker, in hypertensive patients with primary aldosteronism

Associations Between Changes in Plasma Renin Activity and Aldosterone Concentrations and Changes in Kidney Function After Treatment for Primary Aldosteronism

Long‐term effects of primary aldosteronism treatment on patients with primary aldosteronism and chronic kidney disease

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