Examinando por Autor "Baudrand, René"

Mostrando 1 - 2 de 2
  • Miniatura
    Ítem
    Primary Aldosteronism in a Hispanic Cohort: Responses to Mineralocorticoid Receptor Antagonism and Remission in a Case
    (Oxford University Press, 2025-02) Tapia-Castillo, Alejandra; Vecchiola, Andrea; Quiñones, Paola; Baudrand, René; Uslar, Thomas; Delgado, José; Carvajal, Cristian A.; Fardella, Carlos E.
    Background: Primary aldosteronism (PA) is the main cause of secondary arterial hypertension. In this study, we present the medical treatment of Hispanic patients with PA followed for up to 5 years, highlighting the complete cure with pharmacological treatment in one of our patients. Methods: We studied 32 PA patients, followed every 6 months after starting MRA. A clinical response was the normalization of blood pressure (BP) in the absence of other antihypertensive drugs. The biochemical response was considered with normalization of potassium and renin. Responses to treatment were compared using the defined daily dose (DDD). The effect of MRA was evaluated in vitro. The HAC15 cells were cultured and stimulated with aldosterone and spironolactone for 24-72 h, and the apoptotic cell death was measured. Results: At 12 months posttreatment with MRA, 68% of the patients had a total clinical response, and 67% had a total biochemical response. Response to MRA treatment reduced DDD by an average of 74%. Additionally, we observed one PA patient treated with spironolactone after 3 years, he presented a pharmacological cure with normalization of aldosterone and renin without treatment with spironolactone. The in vitro study shows that spironolactone increased early apoptosis by 60% and late apoptosis by 50%. Conclusions: These results suggest the importance of timely diagnosis of PA and specific treatment with MRA, especially in patients with a poor response to treatment. Moreover, remission of PA may occur in some patients after spironolactone treatment due to its suggestive role as an apoptotic agent.
  • Miniatura
    Ítem
    Progressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines
    (Endocrine Society, 2024-09) Uslar, Thomas; Newman, Andrew J.; Tapia-Castillo, Alejandra; Carvajal, Cristian A.; Fardella, Carlos E.; Allende, Fidel; Solari, Sandra; Tsai, Laura C.; Milks, Julia; Cherney, Michael; Stouffer, David G.; Auchus, Richard; Brown, Jenifer M.; Baudrand, René; Vaidya, Anand
    Background: It has been postulated that chronic kidney disease (CKD) is a state of relative 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) insufficiency, resulting in increased cortisol-mediated mineralocorticoid receptor (MR) activation. We hypothesized that relative 11βHSD2 insufficiency manifests across a wide spectrum of progressively declining kidney function, including within the normal range. Methods: Adult participants were recruited at 2 academic centers. A discovery cohort (n = 500) enrolled individuals with estimated glomerular filtration rate (eGFR) ranging from normal to CKD stage 5, in whom serum cortisol-to-cortisone (F/E) was measured as a biomarker of 11βHSD2 activity. A validation cohort (n = 101) enrolled only individuals with normal kidney function (eGFR ≥ 60 mL/min/1.73 m2) in whom 11βHSD2 activity was assessed via serum F/E and 11-hydroxy-to-11-keto androgen (11OH/K) ratios following multiple maneuvers: oral sodium suppression test, dexamethasone suppression test (DST), and ACTH-stimulation test (ACTHstim). Results: In the discovery cohort, lower eGFR was associated with higher F/E (P-trend < .001). Similarly, in the validation cohort, with normal eGFR, an inverse association between eGFR and both F/E and 11OH/K ratios was observed (P-trend < .01), which persisted following DST (P-trend < .001) and ACTHstim (P-trend < .05). The fractional excretion of potassium, a marker of renal MR activity, was higher with higher F/E (P-trend < .01) and with lower eGFR (P-trend < .0001). Conclusion: A continuum of declining 11βHSD2 activity was observed with progressively lower eGFR in individuals spanning a wide spectrum of kidney function, including those with apparently normal kidney function. These findings implicate cortisol-mediated MR activation in the pathophysiology of hypertension and cardiovascular disease in CKD.