Efficacy and safety of finerenone in the treatment of primary aldosteronism: A prospective clinical study.

Hypokalemic Nephropathy

To determine whether changes in serum glucose, serum potassium, and plasma insulin levels are correlated in a cohort of hypertensive patients. Prespecified subgroup analysis of results from a prospective, multicenter, randomized, open-label, parallel-group study. Setting. Primary care clinics at three tertiary care medical centers. Community-based ambulatory population of 202 patients (age range 17-65 yrs) with a new diagnosis of hypertension, untreated hypertension, or known hypertension, who were previously treated with fewer than three antihypertensive drugs and had no evidence of cardiovascular disease or diabetes mellitus. Intervention. Monotherapy with oral hydrochlorothiazide 12.5 or 25 mg/day for 9 weeks. Fasting serum glucose, serum potassium, and plasma insulin levels were obtained at baseline (before hydrochlorothiazide therapy was started) and after 9 weeks of therapy. Significant elevations were noted in fasting serum glucose (mean +/- SD 3.42 +/- 10.38 mg/dl, p<0.0001) and plasma insulin (2.35 +/- 9.47 microU/ml, p<0.0001) levels, and a significant reduction in serum potassium level (0.30 +/- 0.44 mEq/L, p<0.0001) was noted. No significant correlation was observed between changes in fasting serum glucose and potassium levels (r = 0.022, 95% confidence interval (CI) -0.120-0.164, p=0.757) or between changes in serum potassium and plasma insulin levels (r = -0.112, 95% CI -0.256-0.037, p=0.140). Changes in serum glucose levels did not differ significantly between patients maintaining serum potassium levels of 4.0 mEq/L or greater and those with levels below 4.0 mEq/L. Changes in serum potassium and serum glucose levels were not correlated in individuals receiving hydrochlorothiazide monotherapy; thus maintenance of normal potassium levels may not attenuate the risk of thiazide diuretic-induced hyperglycemia.

Diagnosis and treatment of primary aldosteronism (PA) in chronic kidney disease (CKD) may be deferred due to limited evidence supporting safety and efficacy of treatment. Our goal was to assess clinical outcomes in patients with PA and CKD who received surgical or medical management. We conducted a multicenter, retrospective cohort study of patients with PA and CKD who underwent adrenal vein sampling from 2009-2019. We characterized clinical outcomes and evaluated differences by surgical versus medical management. Primary outcomes were systolic blood pressure and number of antihypertensive medications. Secondary outcomes were diastolic blood pressure, serum potassium, estimated glomerular filtration rate (eGFR), and kidney and cardiovascular events. Analyses were adjusted for age, sex, race, cardiovascular disease, diabetes, and eGFR. Of 239 participants with PA and CKD, 158 (66%) underwent adrenalectomy, and 81 (34%) were treated medically. Mean age was 57±10 years, 67% were female, mean eGFR was 45±12 mL/min per 1.73 m2, and 49% were on potassium supplementation. At 5 years, mean blood pressure decreased from 149±22/85±14 to 131±28/78±16 mm Hg and mean number of antihypertensive medications decreased from 4.0±1.5 to 2.4±1.4. Adrenalectomy, compared to medical management, was associated with similar systolic blood pressure (-0.90 mm Hg [95% CI, -6.99 to 5.07]) but fewer medications (1.7 [95% CI, -2.24 to -1.10]), and no difference in potassium levels or kidney or cardiovascular outcomes. Patients with PA and CKD are likely to benefit from either surgical adrenalectomy or medical management. Detection and treatment of PA may help to reduce blood pressure and medication burden in patients with CKD.

Disclosure: K. Aiga: None. M. Kometani: None. D. Aono: None. S. Karashima: None. T. Yoneda: None. Primary aldosteronism (PA) is a major cause of secondary hypertension. PA is known to have higher prevalence of cerebral or cardiovascular complications, indicating the importance of early detection and treatment for PA. PA is caused by autonomous secretion of aldosterone in the adrenal glands. PA is characterized by high plasma aldosterone concentration, low plasma renin activity and hypokalemia. PA is classified into unilateral PA (aldosterone-producing adenoma [APA] or unilateral hyperplasia) and bilateral PA (bilateral adrenal hyperplasia). PA with aldosterone excess in bilateral adrenal glands is defined as bilateral PA. On the other hand, PA with aldosterone excess in unilateral adrenal gland is defined as unilateral PA. Strategies for PA treatment depends on the subtype of PA. Medication by mineralocorticoid receptor antagonists is a common treatment for bilateral PA. Adrenalectomy is the most efficient treatment for unilateral PA. In general, patients tend to maintain normal serum potassium level and blood pressure after adrenalectomy, and recurrence of PA is extremely rare. Recently, mutation in the gene named KCNJ5 was found to derive APA. Herein, we report two cases of PA recurrence more than 10 years after surgical treatment for APA. Somatic mutation in KCNJ5 was detected in the first occurrence of PA in both cases. First case, a 52-year-old woman was examined for hypertension 22 years after total adrenalectomy of the right adrenal gland. Recurrent PA was diagnosed based on high aldosterone-renin-ratio (ARR), identification of left adrenal gland tumor by computed tomography (CT), and a confirmatory test. Second case, a 65-year-old man was examined for hypertension 17 years after total adrenalectomy of the left adrenal gland. He had maintained his blood pressure using medication since the onset of hypertension 4 years after the surgery. A year later, a high ARR was observed. PA recurrence was determined by a right adrenal gland tumor noted on CT and a confirmatory test. Tissues of the adrenal gland were obtained from adrenalectomy in both cases. Histopathological analysis revealed presence of one adenoma in the first case, while two adenomas were confirmed in the second case. Somatic mutation in KCNJ5 gene was detected in both cases. To date, there are no specific guidelines established for the management of recurrent PA. Early detection is crucial for the prevention of severe cardiovascular diseases. Long-term follow-up is recommended after the treatment of PA. Presentation: Friday, June 16, 2023

Hypertension Editors' Picks: Hyperaldosteronism.

confound, and even invert, the lateralization in about 24% of the patients, 7 for reasons that are discussed in depth elsewhere.

Six patients with primary aldosteronism (PA), one with idiopathic hyperaldosteronism (IHA), one with glucocorticoid responsible hyperaldosteronism (GRHA) and eight with essential hypertension (EH) were treated with trilostane (MWD-1822) (4 alpha, 5-epoxy-17 beta-hydroxy-3-oxo-5 alpha-androstane-2 alpha-carbonitrile), an inhibitor of adrenal steroid biosynthesis, for 9-47 days with a daily dose of 30-960 mg. Blood pressure decreased slightly and gradually from 30 min. to 360 min, plasma aldosterone (PAC) and cortisol concentration (F) decreased, and plasma dehydroepiandrosterone concentration (DHEA) increased 120 min. after the administration of a single dose of 120 mg of trilostane. In the patients with PA, IHA and GRHA on long term therapy with trilostane, blood pressure decreased, PAC and F were depleted, serum improved within normal limits and DHEA increased, but plasma progesterone concentration (Prog.) changed variously and plasma renin activity (PRA) remained suppressed. In the patients with EH, systolic pressure decreased in 5 out of 8 (under - 20 mmHg), and diastolic pressure decreased in 3 out of 8 (under - 10 mmHg), DHEA increased in all, but the changes in serum potassium, PAC, F, Prog. and PRA were various. There was no remarkable reaction after the administration of trilostane. It is concluded that trilostane is an effective inhibitor of 3-hydroxysteroid dehydrogenase in vivo and that it is useful in the treatment of primary aldosteronism and other hypertension due to hyperproduction of aldosterone.

To the Editor: Experimental and clinical evidence suggests that aldosterone excess is associated with adverse cardiovascular sequelae, including remodeling, fibrosis, left ventricular (LV) dysfunction, stroke, myocardial infarction, and arrhythmias, independent of its effects on blood pressure (BP).1 Although the underlying mechanisms have yet to be fully elucidated, results from animal studies suggest the involvement of inflammatory pathways.1 Familial hyperaldosteronism type 1 (glucocorticoid remediable aldosteronism [FH-1]) is a rare form of primary aldosteronism in which inheritance of a “hybrid” 11β-hydroxylase/aldosterone synthase gene leads to excessive aldosterone production regulated by corticotropin rather than renin-angiotensin.2 Genetic testing has permitted the identification of individuals with FH-1 with biochemical evidence of aldosterone excess but normal BP, providing a unique opportunity to investigate adverse effects of aldosterone excess without the confounding influences of BP elevation. We have reported previously that these individuals have increased echocardiographically measured LV wall thicknesses and reduced LV diastolic function when compared with normotensive controls matched for age, sex, and BP.3 In the current study, we sought evidence in these same individuals of aldosterone-mediated cardiovascular inflammation by comparing their blood levels of 3 markers of inflammation (interleukin 6 [IL-6], osteopontin …

Severe hypokalemia after budesonide treatment for Crohn's disease.

Disclosure: T. Vo: None. F. El Sayed: None. M. Taleb: None. D. McVinnie: None. S. Athimulam: None. Background: Primary aldosteronism (PA) is a condition of excessive aldosterone, leading to hypertension and increased risk of cardiovascular and kidney complications. Effective therapy reverses complications, normalizes potassium levels, controls blood pressure, and potentially reduces pill burden. Objective: To determine racial differences in renal outcomes of PA patients who underwent medical or surgical intervention Design: Retrospective study of PA patients who underwent adrenal vein sampling (AVS) over a 12-year period Setting: Academic tertiary care setting Main outcomes measured: Blood pressure (BP), serum potassium, serum creatinine (Cr) and estimated glomerular filtration rate (eGFR) pre and post treatment for PA, and number of anti-hypertensive medications Results: 113 patients with PA who underwent AVS with a median age of 58 years [36 White (32%), 77 Black (68%)] were included. No significant differences in age or BMI between races. 48 patients underwent adrenalectomy (Black n=30, 63% and White n=18, 37%) and 65 patients were treated medically with mineralocorticoid antagonists (MRA) (Black n=47, 72% and White n=18, 28%). Baseline findings: (i) White patients had higher mean systolic BP (Black 149 vs White 155 mmHg, p = 0.03), (ii) Black patients had higher mean serum creatinine (Black 1.1 vs White 0.91 mg/dL, p = 0.05), and lower potassium compared to White patients (Black 2.9 vs White 3.1 mEq, p = 0.047). No significant differences in diastolic BP, number of BP medications, and mean total daily dose of MRA between races. Overall, patients had significant improvement in both systolic and diastolic BP following intervention (medical, surgical, or both). Mean systolic BP decreased (pre 151 vs post 129 mmHg, p &amp;lt; 0.0001), and mean diastolic BP decreased (pre 90 vs post 80 mmHg, p &amp;lt; 0.0001) with treatment. However, serum creatinine level increased (pre 1.0 vs post 1.6 mg/dL, p &amp;lt; 0.0001) and mean eGFR declined (pre 83 vs post 65 mL/min/1.73 m², p &amp;lt; 0.0001) after treatment. Patients who underwent adrenalectomy had higher mean serum potassium (surgical 3.9 vs medical 3.5 mEq, p&amp;lt;0.0001), required fewer average number of BP medications (surgical 1.7 vs medical 2.5, p = 0.0006), and had lower BP compared to those managed medically, although not statistically significant. At the end of the study period, there was no significant difference between serum potassium or systolic and diastolic BP between Black and White patients. Black patients required more antihypertensives for BP control. Conclusion: Patients with PA who undergo adrenalectomy require fewer antihypertensives and have higher serum potassium than those managed medically. While treatment improves blood pressure and potassium levels, renal function continues to decline, underscoring the need for early diagnosis and timely intervention to prevent chronic kidney disease. Presentation: Monday, July 14, 2025

Objectives: Preeclampsia is a pregnancy-related multisystem medical disorder which adversely affects the health of the mother and fetus. Studies have shown varied changes in biochemical renal function indices in preeclampsia. These changes vary in different environments and affect renal health and pregnancy outcomes. Accordingly, this study aimed to determine changes in serum electrolytes, urea, and creatinine in women with preeclampsia in Calabar. Materials and Methods: A cross-sectional comparative study was conducted on 144 pregnant women including 72 normotensive and 72 preeclamptic cases of similar age groups, with singleton pregnancies, and in the third trimester. The serum sodium, potassium, bicarbonate, chloride, urea, and creatinine were assayed in the two groups. Finally, statistical analysis was done using SPSS, version 22. Results: Based on the results, the preeclamptic group had significantly higher mean blood pressure (BP) and body mass index (BMI) compared to the normotensives. In addition, women with preeclampsia had a significant decrease in serum potassium and an increase in the serum creatinine compared to the normotensive group. The results further revealed that serum potassium, as well as systolic BP and diastolic BP had a significant inverse correlation in preeclampsia (P &lt; 0.01 and P &lt; 0.05, respectively). Eventually, the serum creatinine had a significant positive relationship with systolic and diastolic BP (P &lt; 0.01) Conclusions: In general, serum potassium and creatinine levels significantly altered in preeclampsia and were associated with increased disease severity. Therefore, it is suggested the serial electrolyte and creatinine profile should be used in the monitoring disease severity, which informs a timely intervention and reduces complications associated with preeclampsia.

In primary aldosteronism (PA), non-suppressible excessive aldosterone secretion due to dietary salt intake significantly contributes to hypertension and cardiovascular complications. Blocking the overactivation of mineralocorticoid receptors (MRs) with mineralocorticoid receptor antagonists (MRAs) is a cornerstone for the medical treatment of PA. However, the role of MRAs in controlling hypertension remains unclear. This study aimed to explore the relationship between changes in body composition parameters (determined by bioelectrical impedance analysis), blood pressure (BP) levels, serum potassium (K+) levels and Study 36-Item Short-Form Health Survey (SF-36) scores after MRA treatment in 50 patients with PA. Treatment with MRAs significantly decreased the systolic BP (SBP) and diastolic BP (DBP) levels and extracellular water (ECW) volume, while it increased the serum K+ levels, active renin concentrations (ARCs), and scores on several SF-36-based quality of life (QOL) subscales. ECW change (ΔECW) and serum K+ change were not significantly associated with changes in SBP and DBP levels. ΔECW showed a significant inverse correlation with ΔARC, suggesting that ARC increases with decreasing ECW volume due to renal MR activity blockade and that ARC is a highly sensitive indicator of ECW volume. In the stratified analysis of patients with PA, ECW volume was significantly decreased in those aged ≥60 years and those with a body mass index of ≥25 kg/m2. In conclusion, MRA treatment showed antihypertensive, biochemical, and QOL improvement effects in patients with PA. The antihypertensive effect may not be related to the decrease in ECW volume due to renal MR activity blockade. Evaluation of ECW using BIA in patients with PA treated with MRAs. Abbreviations: ARC, active renin concentration; BIA, bioelectrical impedance analysis; BMI, body mass index; BP, blood pressure; ECW, extracellular water; K+, serum potassium; MRA, mineralocorticoid receptor antagonist; PA, primary aldosteronism; QOL; quality of life; Δ, parameter changes after MRA treatment.

Finerenone is a novel nonsteroidal mineralocorticoid receptor antagonist. However, robust evidence about its efficacy and safety in primary aldosteronism is scarce. In this prospective, multicenter, single-arm, and exploratory trial, we enrolled adults (aged ≤75 years) with primary aldosteronism, an office blood pressure (BP) ranging from 140 to 180/90 to 120 mm Hg, and an estimated glomerular filtration rate ≥60 mL/min per 1.73 m². Eligible patients received finerenone (20-40 mg/d) treatment for 12 weeks. The primary outcome was the change in daytime systolic BP at 12 weeks. Fifty-seven patients were ultimately treated. Per-protocol analysis revealed that finerenone treatment significantly reduced mean daytime systolic BP (-6.69±1.60 mm Hg; P<0.001) and diastolic BP (-4.55±1.06 mm Hg; P<0.001) according to ambulatory monitoring. Mean office BP decreased even more substantially (systolic BP, -15.58±1.69 mm Hg; diastolic BP, -8.61±1.02 mm Hg; both P<0.001). The mean increase in serum potassium concentration was 0.39±0.05 mmol/L, and 94.5% of patients exhibited a normal concentration after 12 weeks of treatment (versus baseline 61.8%; P<0.001). Plasma renin activity increased, and 32.7% of patients exhibited a plasma renin activity concentration ≥1 ng/mL per h. According to the Primary Aldosteronism Medical Treatment Outcome criteria, 29.1% and 20.0% of patients achieved complete biochemical and clinical responses, respectively. Treatment was well tolerated. This study demonstrated the efficacy and safety of finerenone in the treatment of primary aldosteronism, supporting its use as a potential alternative therapy for the condition. Nevertheless, further prospective and head-to-head randomized controlled trials are essential to establish finerenone as a viable substitute for spironolactone. URL: https://www.clinicaltrials.gov; Unique identifier: NCT06381323.

My answer is “no.” Although primary aldosteronism (PA) is likely more common than most experts believed in the 1960–1990 interval, it is not nearly as common as Dr Calhoun and other investigators report from 1990 until now. As many younger clinicians may not remember, this same issue arose soon after Dr Jerome Conn characterized this disease in 1955.1 Reporting on the prevalence of PA in his highly referred population of likely suspects, Dr Conn and coworkers’ estimates were as high as 20%.2 Subsequently, studies on unreferred patients supported a prevalence of <1%.3 The lower estimate was commonly accepted until Gordan and colleagues started screening for PA with the plasma aldosterone:renin ratio (ARR) first described in 19764 and expanded by Hiramatsu et al in 1981.5 In 1993, Gordon et al6 reported an elevated ARR in 20% of 199 patients, with 8.5% having an abnormal saline suppression test and 2.5% proven to have an aldosterone-producing adenoma. Since then, numerous series have been reported (Table). As seen in Table 1, the prevalence of an elevated ARR has varied from 5.5% to 39.0%. Part of the wide variation rises from the use of varying thresholds; more of the variation rises from inclusion of various types of patients. The latter point must be recognized, because most patients in these series were referred to specialized centers, just as Dr Conn’s high numbers were largely derived from a referred population. View this table: Prevalence of Autonomous Hyperaldosteronism and APAs in Patients Tested by ARR Two recently published series epitomize the vagaries of most series listed in the Table. The first is a study of 1125 recently diagnosed subjects with hypertension referred to 14 specialized hypertension clinics throughout Italy.27 Plasma renin activity and plasma aldosterone were measured at baseline and again 60 …

Aim: To observe the mean alteration in potassium levels one-hour post-antihyperkalemic treatment in end stage renal disease patients presenting with hyperkalemia. Study design: Quazi interventional (experimental) study. Place and duration of study: Department of Medicine, Sir Ganga Ram Hospital Lahore from 28th June 2018 to 27th December 2018. Methodology: Sixty patients of both genders with age range between 14 to 70 years having stage 5 CKD (thrice-weekly dialysis dependent) for at least 6 months with raised serum potassium (&gt;5.5 mEq/L). These patients were given medical treatment in the form of salbutamol nebulization, injectable calcium gluconate, and 100ml 25% dextrose water solution neutralized with Humulin R Insulin 12 units. Serum potassium was reassessed 1 hour after the treatment. Mean change in serum potassium was observed and was compared across various subgroups of patients. A written informed consent was taken from each patient. Results: In the current study, mean age of our studied population was 50.6±10.4 years with male-gender dominance (81.7%). Mean ESRD duration was 11.8±3.7 months while the mean BMI was 27.6±3.6Kg/m2. 15 (25.0%) patients were obese. The serum potassium level at presentation ranged from 5.6mEq/L to 6.9mEq/L with a mean of 6.25±0.39mEq/L. The serum potassium level 1 hour after medical treatment ranged from 4.8mEq/L to 6.3mEq/L with a mean of 5.58±0.43mEq/L. This change in mean serum potassium was significant (p-value&lt;0.001) on paired sample t-test. The change in serum potassium level ranged from 0.5-0.9mEq/L with a mean of 0.676±0.123mEq/L. Similar mean change in serum potassium level was observed when stratified for age, gender, BMI and duration of ESRD. Keywords: End Stage Renal Disease, Hemodialysis, Hyperkalemia, Medical Treatment