Phase III interventional study to evaluate the different efficacy of Torasemide and Spironolactone in reducing systolic blood pressure in carriers and non-carriers of the different genotypic combinations for Lanosterol and Uromodulin

The investigators will enroll 144 naïve hypertensive subjects who will undertake 2-4 weeks of run-in and 4 weeks of treatment (7 day window at each visit). During this period partecipants will follow a low sodium diet (about 5g/day) and will be monitored with blood chemistry tests

Inclusion Criteria:

• male (25-65 years) and female (45-65 years in menopause defined as "12 consecutive months of amenorrhea for which no other physiological or pathological cause has been identified in woman over 45 years of age")

• newly diagnosed hypertensive patients never treated before or on single antihypertensive drug therapy

• hypertension grade I or II (according to 2013 ESH guidelines, in the patient untreated or despite therapy), defined as the following:

  • at visits T-4 and T-2 (week -4 and week -2 ± 7 days, run-in period) the mean of the last 3 consecutive SBP measurements must be >=140 mmHg and/or diastolic BP>= 90mmHg
  • at the T0 visit (week 0 ± 7 days, enrollment), the mean of the last 3 consecutive systolic BP measurements must be >=140 mmHg and <180 mmHg and diastolic BP must be >=90 mmHg and <110 mmHg

• signing of the informed consent for participation in the study and for genotyping.

Exclusion Criteria:

• known causes of secondary hypertension

• stage II hypertension (SBP>= 180 and SBP>=110 mmHg

• history of renal artery stenosis

• significant kidney disease (eGFR-CK-EPI less than 60 mL/min)

• refractory hypokalemia or hyponatremia (Napl < 126 mEq/L)

• hyperkalemia (K > 5.5 mEq/l)

• hypercalcemia

• symptomatic hyperuricemia

• liver disease (transaminases greater than 3 times the maximum laboratory value)

• cardiac pathologies (previous myocardial infarction, atrial fibrillation in progress, etc.)

• diabetes (fasting blood sugar >126mg/dL)

  -. current statin treatment

• obesity (BMI >30 kg/m2)

• ongoing pregnancy

• breastfeeding in progress

• anuria

• hypovolemia and dehydration

• known hypersensitivity to the study drugs (Spironolactone or Torasemide) or to any of the excipients

• ongoing therapy with aminoglycosides or cephalosporins

• participation in a clinical study in which an investigational drug was administered within 30 days or 5 half-lives prior to the study drug

• patients unable to express valid consent

IDP will be stored in the institutional repository.

The study will be double-blind with respect to the genetic analysis and open-label with an observer blind with respect to the primary endpoint.