Thiazides and thiazide-like diuretics are one of the five major classes of antihypertensive drugs. This study is to investigate whether urinary PGE2 concentration at baseline (prior to thiazide initiation) is associated with the development of TIH within the first four weeks of treatment.
Thiazides and thiazide-like diuretics are one of the five major classes of antihypertensive drugs. They act by inhibiting the apical Na+-Cl- -cotransporter in the distal convoluted tubules of the kidneys. Thiazides and thiazide-like diuretics often cause adverse effects, importantly a drop in plasma sodium levels that is called thiazide-induced hyponatremia (TIH). Data suggest a crucial role of urinary PGE2 in water reabsorption. Since urinary PGE2 concentrations were higher in patients with TIH, quantification of urinary PGE2 prior and after thiazide initiation might allow identification of patients at risk for TIH, presenting PGE2 as a potential novel predictive marker for the development of TIH. This study is to investigate whether urinary PGE2 concentration at baseline (prior to thiazide initiation) is associated with the development of TIH within the first four weeks of treatment. Hospitalized and ambulatory patients in whom a thiazide or thiazide-like diuretic will be newly prescribed are screened for inclusion. The study procedure contains the screening and inclusion, visit 1 before thiazide initiation, visit 2 4 weeks (+/-7days) after thiazide initiation and a 3-months follow-up (visit 3). An additional visit (visit 2.1) will only be added in case of a dose change of the thiazide or thiazide-like diuretic (4 weeks +/- 7 days after the dose change). The 2 hours- challenge is optional if the patient agrees to additional testing.
Study Type
OBSERVATIONAL
Enrollment
232
Collection of spot urine, blood sampling, vital parameters, body weight, medical history, patient questionnaires, drinking protocol, drug diary at at Visit 1 (before thiazide initiation), at Optional 2 hours-challenge, at Visit 2 (4 weeks after thiazide initiation), at Visit 2.1 (4 weeks after dose change), at Visit 3 (3-months after thiazide initiation)
Hospital Universitario de Móstoles
Móstoles, Spain
RECRUITINGUniversity Hospital Basel, Endocrinology, Diabetes and Metabolism
Basel, Switzerland
RECRUITINGKantonsspital Baselland
Liestal, Switzerland
RECRUITINGOccurrence of hyponatremia (plasma sodium <135 mmol/L)
Occurrence of hyponatremia (plasma sodium \<135 mmol/L)
Time frame: Within the first four weeks of treatment (at visit 2)
Change in urinary Prostaglandin- concentration
Change in urinary Prostaglandin E2 (PGE2) and metabolite (PGE2M)- concentration
Time frame: Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months
Change in the expression of proteins involved in sodium and water transport
Change in the expression of proteins involved in sodium and water transport (AQP2, Prostaglandin transporter (PGT) and NCC) in urinary extracellular vesicles in spot urine (second morning urine)
Time frame: Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months
Change in systolic and diastolic blood pressure
Change in systolic and diastolic blood pressure
Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in heart rate
Change in heart rate
Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in body weight
Change in body weight
Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in daily fluid intake
Change in daily fluid intake
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Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in Bioelectrical impedance analysis (BIA)
Change in Bioelectrical impedance analysis (BIA)
Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in plasma sodium
Change in plasma sodium
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in urine sodium
Change in urine sodium
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in potassium
Change in potassium
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in chloride
Change in chloride
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in creatinine
Change in creatinine
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in urea
Change in urea
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in uric acid
Change in uric acid
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in general well-being
Change in general well-being rated on a visual analogue scale reaching from 0 to 10
Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Incidence of hyponatremia
Incidence of hyponatremia
Time frame: Between baseline and visit 3, approximately 3 months
Incidence of falls
Incidence of falls
Time frame: Between baseline and visit 3, approximately 3 months
Incidence of fractures
Incidence of fractures
Time frame: Between baseline and visit 3, approximately 3 months
Incidence of hospitalization due to any cause
Incidence of hospitalization due to any cause
Time frame: Between baseline and visit 3, approximately 3 months