Antihypertensive Effect of Long-Term Monotherapy with Esaxerenone in Patients with Essential Hypertension: Relationship Between Baseline Urinary Sodium Excretion and Its Antihypertensive Effect.

INTRODUCTION: The blood pressure (BP) control mechanism for mineralocorticoid receptor blockers is unclear, and analysis of their use as a single agent in the clinical setting is required to resolve this uncertainty. There is a paucity of data on esaxerenone monotherapy assessing its long-term antihypertensive effect and urinary biomarkers. METHODS: This post hoc exploratory substudy of a long-term phase 3 study evaluated the effect of esaxerenone monotherapy (2.5 or 5 mg/day) in treatment-naïve patients who continued the therapy during the 52-week study period (n = 25). In addition to blood biomarkers, urinary biomarkers were also assessed in 24-h urine collection samples. RESULTS: Esaxerenone monotherapy was associated with consistent reductions in systolic/diastolic BP in the substudy population (- 23.5/- 13.1 mmHg at week 52, p < 0.001 vs baseline). Plasma aldosterone concentrations and plasma renin activity significantly increased during esaxerenone monotherapy at all time points. On the basis of the observations that both urine volume and urinary sodium excretion also decreased up to the end of the study, and were significantly lower at 12 weeks, patients were further categorized into higher/lower urinary sodium excretion subgroups according to whether their baseline values were above or below the median. In the group with higher baseline urinary sodium excretion, esaxerenone exhibited a significantly greater decrease in systolic/diastolic BP compared to the lower baseline group. CONCLUSION: Esaxerenone exhibited sustained and stable antihypertensive activity even when administered as a single agent for 52 weeks in patients with essential hypertension. The additional urinary biomarker analysis suggests that the BP-lowering effects of esaxerenone may be partly exerted via mechanisms related to salt and water retention, and that the effect is particularly pronounced in patients with hypertension and higher baseline urinary sodium excretion, which may reflect a state of excessive salt intake. TRIAL REGISTRATION: NCT02722265.

[Impact of the ExSel(®) test administration on the excessive salt consumption in hypertensive patients followed in general practice]. / Conséquences de la réalisation du test ExSel(®) sur la consommation excessive de sel chez des patients hypertendus suivis en médecine générale.

OBJECTIVE: To evaluate the impact of the Exsel(®) test administration on salt intake in hypertensive subjects followed in general practice. METHOD: In a group practice of general practitioners in the Île-de-France, the ExSel(®) test http://www.comitehta.org/testez-vous/consommez-vous-du-sel-en-exces-test-exsel/ was administered to 329 outpatients. The questionnaire was filled in the waiting room and then commented by the doctor. In patients treated for hypertension, 24hours urinary Na was prescribed after the consultation. Excessive salt consumption (ESC) was defined as a urinary Na≥200mmol/day. RESULTS: The population included subjects aged on average 57 years with 43 % of hypertensive patients. According Exsel(®), an ESC was suspected in 36 % of patients and was more common in treated hypertensive patients (44 %; [36-52]) in hypertensive men (57 %; [46-68]) than among non-hypertensive (31 %; [24-38]) and non hypertensive women (18 % [11-25]). Urinary Na has been finally performed by 63 % of subjects and 24hours excretion was 157±56mmol in men and 123±39mmol in women. After this 24hours urinary sodium evaluation, subsequent to ExSel(®) test, ESC frequency was lower among men (19 %) and very low among women (5 %). CONCLUSION: To estimate the ESC, the ExSel(®) test is easily performed in general practice while 24hours urinary sodium is more difficult to obtain. Achieving an ExSel(®) test was accompanied by a decrease in the frequency of excessive salt consumers with a greater effect in women.

[Development and evaluation of ExSel Test to screen for excess salt intake in hypertensive subjects]. / Mise au point et évaluation de l'ExSel Test pour dépister une consommation excessive de sel chez les patients hypertendus.

OBJECTIVE: Development of a test to screen excess salt intake (ESI) in hypertensive patients. METHODS: Hypertensive subjects living in Paris area have been included. A 24-hour urinary sodium collection has been performed the day before the visit for a day hospital. A food diary was completed on the day of the urine collection and validated after an interview with a dietetician. An ESI was defined by a urinary sodium ≥ 200mmol/d. Clinical or food characteristics associated to an ESI were retained for the ExSel Test variables. A ROC curve was performed to determine the optimal score for the ExSel Test in detection of ESI in hypertensive patients. RESULTS: One hundred and forty-eight hypertensive patients have been included living in the Île-de-France area. ESI was observed in 19% with a higher frequency in men. Seven major determinants of ESI have been identified and are the questions that constitute the ExSel Test. A positive response assigns points: man (1); BMI > 30 (2); bread 4 or 5 pieces per day (1) or more than 6 pieces; cheese at least 1 time per day (2); charcuterie at least 2 times per week (2); use of processed broth or pilaf (1); food rich in hidden salt (pizza, cheeseburger, quiche, shrimp, potato chips, smoked fish, olive) at least 2 times per week (1). The ROC curve analysis shows that a score of 5 or more has the best Youden index with a sensitivity of 0.63, specificity of 0.95, PPV of 0.75, NPV of 0.92. CONCLUSIONS: In hypertensive subjects, an excessive salt intake can be detected by the realization of the ExSel Test based only on a simple food-questionnaire and some clinical parameters. For a clinical use of the ExSel Test, an electronic version is available on http://www.comitehta.org.

A Case of Hypernatremia by Folk Remedies in a CRF Patient / 대한신장학회잡지

We report a case of chronic hypernatremia caused by excessive salt intake as folk remedies for three months. The patient had chronic tubulointerstitial nephritis (CTIN), but without documented cognitive or psychiatric disorders. She presented with severe hypernatremia 189 mmol/L and general weakness. Fluid therapy was done initially with isotonic and then with 0.45% hypotonic saline until serum sodium level reached to 157 mmol/L. Finally hemodialysis was supplemented to achieve normal serum sodium level, and she recovered without any sequelae. This report might be the first case of chronic hypernatremia due to voluntary ingestion of excessive salt in an adult patient with CTIN but without cognitive or psychiatric disorders.