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Bariatric Surgery Induces a Differential Effect on Plasma Aldosterone in Comparison to Dietary Advice Alone.
Berney, M, Vakilzadeh, N, Maillard, M, Faouzi, M, Grouzmann, E, Bonny, O, Favre, L, Wuerzner, G
Frontiers in endocrinology. 2021;:745045
Abstract
BACKGROUND AND OBJECTIVES The pathophysiological mechanisms linking weight loss to blood pressure (BP) reduction are not completely understood. The objective of this study was to compare the effect of weight loss after Roux-en-Y gastric bypass (RYGB) on BP, renin-angiotensin-aldosterone system (RAAS), and urinary electrolytes excretion to those of dietary advice. METHODS This was a case-control prospective study including obese patients referred for RYGB (cases) and obese receiving diet advice only (controls). Ambulatory BP, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary electrolytes were measured before (M0) and after intervention (M3: 3 months and M12: 12 months). RESULTS Twenty-five patients were included in the RYGB group and twelve patients in the control group. After 12 months, weight loss (-42 ± 11.5 vs -12.3 ± 6.3 kg in the control group, p=0.001) and decrease in PAC were more pronounced in the RYGB group (-34 ± 76 vs +14 ± 45 pg/ml in the control group, p=0.002). There was no difference in PRA between both groups (-0.08 ± 1.68 vs 0.01 ± 0.37 ng/ml/h, p=0.31). Sodium excretion was more marked in the RYGB group after 3 months only (-89 ± 14.9 vs -9.9 ± 27.9 mmol/day, p=0.009). The decrease in SBP was similar between both groups (-6.9 ± 9.9 vs -7.1 ± 11.9 mmHg in the control group, p=0.96). CONCLUSIONS Bariatric-induced weight loss induces a progressive decrease in PAC independently of PRA and sodium excretion. Whether this decrease in PAC affects target organ damage in the long term remains to be determined. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, identifier NCT02218112.
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Effect of sodium-glucose cotransporter-2 inhibitors on aldosterone-to-renin ratio in diabetic patients with hypertension: a retrospective observational study.
Sawamura, T, Karashima, S, Nagase, S, Nambo, H, Shimizu, E, Higashitani, T, Aono, D, Ohbatake, A, Kometani, M, Demura, M, et al
BMC endocrine disorders. 2020;(1):177
Abstract
BACKGROUND Plasma aldosterone-to-renin ratio (ARR) is popularly used for screening primary aldosteronism (PA). Some medications, including diuretics, are known to have an effect on ARR and cause false-negative and false-positive results in PA screening. Currently, there are no studies on the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors, which are known to have diuretic effects, on ARR. We aimed to investigate the effects of SGLT2 inhibitors on ARR. METHODS We employed a retrospective design; the study was conducted from April 2016 to December 2018 and carried out in three hospitals. Forty patients with diabetes and hypertension were administered SGLT2 inhibitors. ARR was evaluated before 2 to 6 months after the administration of SGLT2 inhibitors to determine their effects on ARR. RESULTS No significant changes in the levels of ARR (90.9 ± 51.6 vs. 81.4 ± 62.9) were found. Body mass index, diastolic blood pressure, heart rate, fasting plasma glucose, and hemoglobin A1c were significantly decreased by SGLT2 inhibitors. Serum creatinine was significantly increased. CONCLUSION SGLT2 inhibitor administration yielded minimal effects on ARR and did not increase false-negative results in PA screening in patients with diabetes and hypertension more than 2 months after administration.
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Disentangling the Relationships Between the Renin-Angiotensin-Aldosterone System, Calcium Physiology, and Risk for Kidney Stones.
Bayomy, O, Zaheer, S, Williams, JS, Curhan, G, Vaidya, A
The Journal of clinical endocrinology and metabolism. 2020;(6):1937-46
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CONTEXT Complex relationships between aldosterone and calcium homeostasis have been proposed. OBJECTIVE To disentangle the influence of aldosterone and intravascular volume on calcium physiology. DESIGN Patient-oriented and epidemiology studies. SETTING Clinical research center and nationwide cohorts. PARTICIPANTS/INTERVENTIONS Patient-oriented study (n = 18): Participants were evaluated after completing a sodium-restricted (RES) diet to contract intravascular volume and after a liberalized-sodium (LIB) diet to expand intravascular volume. Cross-sectional studies (n = 3755): the association between 24h urinary sodium and calcium excretion and risk for kidney stones was assessed. RESULTS Patient-oriented study: compared to a RES-diet, a LIB-diet suppressed renin activity (LIB: 0.3 [0.1, 0.4] vs. RES: 3.1 [1.7, 5.3] ng/mL/h; P < 0.001) and plasma aldosterone (LIB: 2.0 [2.0, 2.7] vs. RES: 20.0 [16.1, 31.0] vs. ng/dL; P < 0.001), but increased calciuria (LIB: 238.4 ± 112.3 vs. RES: 112.9 ± 60.8 mg/24hr; P < 0.0001) and decreased serum calcium (LIB: 8.9 ± 0.3 vs. RES: 9.8 ± 0.4 mg/dL; P < 0.0001). Epidemiology study: mean urinary calcium excretion was higher with greater urinary sodium excretion. Compared to a urinary sodium excretion of < 120 mEq/day, a urinary sodium excretion of ≥220 mEq/day was associated with a higher risk for having kidney stones in women (risk ratio = 1.79 [95% confidence interval 1.05, 3.04]) and men (risk ratio = 2.06 [95% confidence interval 1.27, 3.32]). CONCLUSIONS High dietary sodium intake suppresses aldosterone, decreases serum calcium, and increases calciuria and the risk for developing kidney stones. Our findings help disentangle the influences of volume from aldosterone on calcium homeostasis and provide support for the recommendation to restrict dietary sodium for kidney stone prevention.
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Nadir Aldosterone Levels After Confirmatory Tests Are Correlated With Left Ventricular Hypertrophy in Primary Aldosteronism.
Ohno, Y, Sone, M, Inagaki, N, Kawashima, A, Takeda, Y, Yoneda, T, Kurihara, I, Itoh, H, Tsuiki, M, Ichijo, T, et al
Hypertension (Dallas, Tex. : 1979). 2020;(6):1475-1482
Abstract
Left ventricular hypertrophy (LVH) is often seen in patients with primary aldosteronism (PA), and the prevalence of LVH is reportedly higher among patients with PA than patients with essential hypertension. However, the correlation between aldosterone levels and LVH is undefined, and how aldosterone affects LVH in patients with PA remains unclear. We, therefore, retrospectively assessed a large PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) to reveal the factors associated with LVH in patients with PA without suspected autonomous cortisol secretion. In the 1186 patients with PA studied, the basal plasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio did not significantly correlate with left ventricular LV mass index (LVMI) in single or multiple regression analyses. However, the plasma aldosterone concentration after the captopril challenge test or saline-infusion test, which are associated with autonomous aldosterone secretion, correlated significantly with LVMI, even after adjusting for patients' backgrounds, including age and blood pressure. In addition, hypokalemia and the unilateral subtype also correlated with LVMI. Longitudinal subanalysis of medically or surgically treated patients with PA showed significant reductions in LVMI in both the surgery (63.0±18.1 to 55.3±19.5 g/m2.7, P<0.001) and drug treatment (56.8±14.1 to 52.1±13.5 g/m2.7, P<0.001) groups. Our results suggest the autonomous aldosterone secretion level, not the basal aldosterone level itself, is relevant to LVH in patients with PA. In addition, the elevated LVMI seen in patients with PA is at least partially reversible with surgical or medical treatment.
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Interplay Between Statins, Cav1 (Caveolin-1), and Aldosterone.
Haas, AV, Baudrand, R, Easly, RM, Murray, GR, Touyz, RM, Pojoga, LH, Jeunemaitre, X, Hopkins, PN, Rosner, B, Williams, JS, et al
Hypertension (Dallas, Tex. : 1979). 2020;(3):962-967
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Statin use is associated with lower aldosterone levels. We hypothesized that caveolin-1 may be important for the uptake of statins into the adrenal gland and would affect statin's aldosterone-lowering effects. The aim of this study was to test whether the caveolin-1 risk allele (rs926198) would affect aldosterone levels associated with statin use. The Hypertensive Pathotype database includes healthy and hypertensive individuals who have undergone assessment of adrenal hormones. Individuals were studied off antihypertensive medications but were maintained on statins if prescribed by their personal physician. Adrenal hormones were measured at baseline and after 1 hour of angiotensin II stimulation on both high- and low-sodium diets. A mixed-model repeated-measures analysis was employed with a priori selected covariates of age, sex, body mass index, and protocol (low versus high sodium, baseline versus angiotensin II stimulated aldosterone). A total of 250 individuals were included in the study; 31 individuals were taking statins (12.4%) and 219 were not. Among statin users, carrying a caveolin-1 risk allele resulted in a 25% (95% CI, 1-43.2) lower aldosterone level (P=0.04). However, among nonstatin users, carrying a caveolin-1 risk allele resulted in no significant effect on aldosterone levels (P=0.38). Additionally, the interaction between caveolin-1 risk allele and statin use on aldosterone levels was significant (P=0.03). These findings suggest caveolin-1 risk allele carrying individuals are likely to receive the most benefit from statin's aldosterone-lowering properties; however, due to the observational nature of this study, these findings need further investigation.
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Clinical and biochemical outcomes after adrenalectomy and medical treatment in patients with unilateral primary aldosteronism.
Katabami, T, Fukuda, H, Tsukiyama, H, Tanaka, Y, Takeda, Y, Kurihara, I, Ito, H, Tsuiki, M, Ichijo, T, Wada, N, et al
Journal of hypertension. 2019;(7):1513-1520
Abstract
OBJECTIVES Current clinical guidelines of primary aldosteronism recommend adrenalectomy (AdX) for unilateral primary aldosteronism based on the studies showing the potential superiority of AdX over the medical treatment. However, since most medically treated cases consisted of bilateral primary aldosteronism and all surgically treated cases consisted of unilateral primary aldosteronism, the different subtype of primary aldosteronism could be a bias for their effects. This study compared the effects of AdX and medical therapy in patients with unilateral primary aldosteronism confirmed by adrenal vein sampling. METHODS Of the 339 patients with unilateral primary aldosteronism in the Japan Primary Pldosteronism Study data base, unilateral AdX and treatment with mineral corticoid receptor antagonists (MRAs) was done in 276 patients (AdX group) and in 63 patients (MRAs group), respectively. The effects were compared by the clinical (improvement of blood pressure) and biochemical outcomes (improvement of hypokalemia). RESULTS At baseline, use of potassium replacement, plasma aldosterone concentration, aldosterone-to-renin ratio, estimated glomerular filtration rate, and prevalence of adrenal mass on imaging were higher in the AdX group than in the MRAs group. At 6 months after commencement of specific treatment for primary aldosteronism, clinical outcome and biochemical outcome in the AdX group were superior than those in the MRAs group. The difference of the outcome between the two groups were the case even after adjusting for the different clinical backgrounds in the two groups before the specific treatment. CONCLUSION Our study provides evidence that AdX is the first choice of treatment in the patients with unilateral primary aldosteronism in terms of clinical and biochemical outcome.
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Serum potassium is a predictor of incident diabetes in African Americans with normal aldosterone: the Jackson Heart Study.
Chatterjee, R, Davenport, CA, Svetkey, LP, Batch, BC, Lin, PH, Ramachandran, VS, Fox, ER, Harman, J, Yeh, HC, Selvin, E, et al
The American journal of clinical nutrition. 2017;(2):442-449
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BACKGROUND Low-normal potassium is a risk factor for diabetes and may account for some of the racial disparity in diabetes risk. Aldosterone affects serum potassium and is associated with insulin resistance. OBJECTIVES We sought to confirm the association between potassium and incident diabetes in an African-American cohort, and to determine the effect of aldosterone on this association. DESIGN We studied participants from the Jackson Heart Study, an African-American adult cohort, who were without diabetes at baseline. With the use of logistic regression, we characterized the associations of serum, dietary, and urinary potassium with incident diabetes. In addition, we evaluated aldosterone as a potential effect modifier of these associations. RESULTS Of 2157 participants, 398 developed diabetes over 8 y. In a minimally adjusted model, serum potassium was a significant predictor of incident diabetes (OR: 0.83; 95% CI: 0.74, 0.92 per SD increment in serum potassium). In multivariable models, we found a significant interaction between serum potassium and aldosterone (P = 0.046). In stratified multivariable models, in those with normal aldosterone (<9 ng/dL, n = 1163), participants in the highest 2 potassium quartiles had significantly lower odds of incident diabetes than did those in the lowest potassium quartile [OR (95% CI): 0.61 (0.39, 0.97) and 0.54 (0.33, 0.90), respectively]. Among those with high-normal aldosterone (≥9 ng/dL, n = 202), we found no significant association between serum potassium and incident diabetes. In these stratified models, serum aldosterone was not a significant predictor of incident diabetes. We found no statistically significant associations between dietary or urinary potassium and incident diabetes. CONCLUSIONS In this African-American cohort, we found that aldosterone may modify the association between serum potassium and incident diabetes. In participants with normal aldosterone, high-normal serum potassium was associated with a lower risk of diabetes than was low-normal serum potassium. Additional studies are warranted to determine whether serum potassium is a modifiable risk factor that could be a target for diabetes prevention. This trial was registered at clinicaltrials.gov as NCT00415415.
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Aldosterone, mortality, cardiovascular events and reverse epidemiology in end stage renal disease.
Abd ElHafeez, S, Tripepi, G, Mallamaci, F, Zoccali, C
European journal of clinical investigation. 2015;(10):1077-86
Abstract
BACKGROUND Plasma aldosterone is markedly increased in end stage renal disease (ESRD). The relationship between aldosterone, all-cause and cardiovascular (CV) mortality in observational studies performed so far is controversial. DESIGN We investigated the relationship between aldosterone, mortality and CV events in multivariate analyses including nutrition status, inflammation, LV function and fluids volume biomarkers in 278 ESRD patients without heart failure at baseline. RESULTS In univariate analyses aldosterone was an inverse predictor of death (3rd tertile vs. 1st tertile Hazard ratios (HR): 0·58; 95% confidence interval (CI) 0·38-0·90. P = 0·01) and CV events (HR: 0·63; 95% CI 0·41-0·96; P = 0·03). Data adjustment for inflammation and malnutrition biomarkers substantially reduced the inverse relationship between aldosterone, mortality and CV events to be largely not significant (P = 0·31 and P = 0·36, respectively). The same was true by adjusting for volume expansion and LV dysfunction (left atrial volume and atrial natriuretic peptide) biomarkers (P = 0·30 for both outcomes). In a model adjusting for the full set of biomarkers of protein energy wasting/inflammation and volume expansion/LV dysfunction the inverse relationship between aldosterone and death and CV events was nullified (HR for death 0·98, P = 0·93; HR for CV events 0·96, P = 0·87). CONCLUSIONS Aldosterone is an inverse predictor of mortality and CV events in ESRD patients. This seemingly paradoxical relationship is abolished by statistical adjustment for inflammation, protein energy malnutrition, and volume expansion biomarkers indicating that it is the mere expression of the confounding effect of these factors. A clinical trial is needed to establish if aldosterone antagonism may improve clinical outcomes in ESRD.
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Fibroblast growth factor 23 and the antiproteinuric response to dietary sodium restriction during renin-angiotensin-aldosterone system blockade.
Humalda, JK, Lambers Heerspink, HJ, Kwakernaak, AJ, Slagman, MC, Waanders, F, Vervloet, MG, Ter Wee, PM, Navis, G, de Borst, MH, ,
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2015;(2):259-66
Abstract
BACKGROUND Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary sodium restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many patients. Previous studies linked high fibroblast growth factor 23 (FGF-23) levels with volume overload; others linked higher serum phosphate levels with impaired RAAS-blockade efficacy. We hypothesized that FGF-23 reduces the capacity of dietary sodium restriction to potentiate RAAS blockade, impairing the antiproteinuric effect. STUDY DESIGN Post hoc analysis of cohort data from a randomized crossover trial with two 6-week study periods comparing proteinuria after a regular-sodium diet with proteinuria after a low-sodium diet, both during background angiotensin-converting enzyme inhibition. SETTING & PARTICIPANTS 47 nondiabetic patients with CKD with residual proteinuria (median protein excretion, 1.9 [IQR, 0.8-3.1] g/d; mean age, 50±13 [SD] years; creatinine clearance, 69 [IQR, 50-110] mL/min). PREDICTOR Plasma carboxy-terminal FGF-23 levels. OUTCOMES Difference in residual proteinuria at the end of the regular-sodium versus low-sodium study period. Residual proteinuria during the low-sodium diet period adjusted for proteinuria during the regular-sodium diet period. RESULTS Higher baseline FGF-23 level was associated with reduced antiproteinuric response to dietary sodium restriction (standardized β=-0.46; P=0.001; model R(2)=0.71). For every 100-RU/mL increase in FGF-23 level, the antiproteinuric response to dietary sodium restriction was reduced by 10.6%. Higher baseline FGF-23 level was a determinant of more residual proteinuria during the low-sodium diet (standardized β=0.27; P=0.003) in linear regression analysis adjusted for baseline proteinuria (model R(2)=0.71). There was no interaction with creatinine clearance (P interaction=0.5). Baseline FGF-23 level did not predict changes in systolic or diastolic blood pressure upon intensified antiproteinuric treatment. LIMITATIONS Observational study, limited sample size. CONCLUSIONS FGF-23 levels are associated independently with impaired antiproteinuric response to sodium restriction in addition to RAAS blockade. Future studies should address whether FGF-23-lowering strategies may further optimize proteinuria reduction by RAAS blockade combined with dietary sodium restriction.
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Aldosterone-to-renin ratio acts as the predictor distinguishing the primary aldosteronism from chronic kidney disease.
Chen, WG, Zhou, TT, Zhou, P, Li, XW, Wu, Z, Zhang, KY, Xing, JC
International journal of clinical and experimental pathology. 2015;(6):6901-9
Abstract
Aldosterone-to-renin ratio (ARR) is a screening test for primary aldosteronism, but it was impacted by a bunch of clinical covariates. The ARR is associated with chronic kidney disease (CKD), renal artery stenosis, renin adenoma. This study aims to investigate relationship between ARR and primary aldosteronism in CKD patients. A retrospective observational analysis involves 253 attendees from Urology Department of Chengdu Military General Hospital (China), comprising 146 patients with confirmed primary aldosteronism, 56 patients with essential hypertension, and 55 patients with chronic kidney disease accounting for primary kidney disease. Blood samples were drawn from patients with particular restriction for measuring serum aldosteronism, plasma renin activity, and serum potassium. Receiver operating characteristic (ROC) curve of ARR was tested to establish cutoff values and to assess sensitivity and specificity. The results showed that LogARR values were significantly higher (P < 0.001), and PRA and serum potassium values were significantly lower (P < 0.001) in primary aldosteronism patients. By contrast, significantly higher serum aldosterone and plasma renin were observed in CKDs compared with the other two groups (P < 0.001). There was a significantly positive correlation between LogARR and serum potassium (r = -0.0345, P < 0.001, R(2) = 0.093). The AUC for plasma renin activity, logARR, and serum aldosterone are 0.855, 0.84, and 0.501, respectively. ROC curve of logARR and plasma renin activity in detection of primary aldosteronism with higher sensitivity and specificity. In conclusion, this study indicated that the ARR act as the biomarker for the primary aldosteronism, and could distinguish from chronic kidney disease.