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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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Abstract
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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Determinants and changes associated with aldosterone breakthrough after angiotensin II receptor blockade in patients with type 2 diabetes with overt nephropathy.
Moranne, O, Bakris, G, Fafin, C, Favre, G, Pradier, C, Esnault, VL
Clinical journal of the American Society of Nephrology : CJASN. 2013;(10):1694-701
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BACKGROUND AND OBJECTIVES Inhibition of the renin-angiotensin-aldosterone system decreases proteinuria and slows estimated GFR decline in patients with type 2 diabetes mellitus with overt nephropathy. Serum aldosterone levels may increase during renin-angiotensin-aldosterone system blockade. The determinants and consequences of this aldosterone breakthrough remain unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study examined the incidence, determinants, and changes associated with aldosterone breakthrough in a posthoc analysis of a randomized study that compared the effect of two angiotensin II receptor blockers in patients with type 2 diabetes mellitus with overt nephropathy. RESULTS Of 567 of 860 participants included in this posthoc analysis, 28% of participants developed aldosterone breakthrough, which was defined by an increase greater than 10% over baseline values of serum aldosterone levels after 1 year of angiotensin II receptor blocker treatment. Factors independently associated with aldosterone breakthrough at 1 year were lower serum aldosterone and potassium levels at baseline, higher decreases in sodium intake, systolic BP, and estimated GFR from baseline to 1 year, and use of losartan versus telmisartan. Aldosterone breakthrough at 6 months was not sustained at 1 year in 69% of cases, and it did not predict estimated GFR decrease and proteinuria increase between 6 months and 1 year. CONCLUSIONS Aldosterone breakthrough is a frequent event 1 year after initiating renin-angiotensin-aldosterone system blockade, particularly in participants exposed to intensive lowering of BP with sodium depletion and short-acting angiotensin II receptor blockers. Short-term serum aldosterone level increases at 6 months are not associated with negative kidney outcomes between 6 months and 1 year.
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Natriuretic and neurohormonal responses to nesiritide, furosemide, and combined nesiritide and furosemide in patients with stable systolic dysfunction.
Sica, D, Oren, RM, Gottwald, MD, Mills, RM, ,
Clinical cardiology. 2010;(6):330-6
Abstract
BACKGROUND In patients with heart failure, few data describe the neurohormonal response to nesiritide and furosemide either alone or in combination. This study systematically compared the effects of nesiritide, furosemide, and their combination on natriuresis/diuresis and plasma aldosterone in patients with chronic stable heart failure who were relatively diuretic resistant. HYPOTHESIS Natriuretic, diuretic, and neurohormonal responses to furosemide and nesiritide will differ when these agents are administered alone vs. in combination. METHODS Twenty-eight subjects completed a multicenter, open-label, three-arm crossover study. Each subject received the following treatments in random order on alternate days: (1) furosemide, 40 mg intravenous bolus; (2) nesiritide, 2 microg/kg intravenous bolus followed by a 0.01 microg/kg/min infusion for 6 hours; (3) both furosemide and nesiritide, with furosemide given at least 15 minutes after initiation of nesiritide. RESULTS Plasma aldosterone increased by 2.2 +/- 1.6 ng/dL after furosemide alone, decreased by 3.9 +/- 1.6 ng/dL after nesiritide alone (P = 0.005 vs furosemide alone and P = 0.56 vs furosemide plus nesiritide), and decreased by 2.8 +/- 1.6 ng/dL after furosemide plus nesiritide (P = 0.02 vs furosemide alone). CONCLUSIONS Furosemide alone produced natriuresis/diuresis and a prompt rise in plasma aldosterone values. Nesiritide alone produced no significant natriuresis/diuresis, but decreased plasma aldosterone values. When furosemide was administered on a background of nesiritide infusion, the observed natriuresis/diuresis was similar to that seen with furosemide alone, without the anticipated increase in plasma aldosterone observed with furosemide alone.