Double Blind Crossover Comparison of Diuretics in the Young

Double Blind Crossover Comparison od Diuretics in Young Patients With Low Renin Hypertension

The principle objective of the study is to determine whether low-renin (i.e. salt sensitive) hypertension at a young age is caused by the kidneys hanging onto too much salt as a result of an over active salt pump in the kidney.

The kidneys have four different salt pumps, and each is blocked by a different type of diuretic (salt losing tablet)If one out of the four is overactive, we would expect patients to respond much better to one diuretic than to the alternatives - rather than responding equally well to all available types of diuretic.

Studies suggest that patients with low renin hypertension respond better to diuretics than other hypertensive drug groups. The aim of the study is to rotate patients through the four main diuretic groups and see if it is possible to identify the most effective diuretic for this group, as measured by a >=10mgHg decrease in Systolic blood pressure in one specific group a compared to the others.

As most caucasians with Low renin hypertension are older (>55), presentation with this type of hypertension at a younger age suggests the presence of substantial genetic variation in order to cause the atypical presentation. It is hoped that by identifying the best diuretic for these patients we will also be able to identify:

1. Whether the young low-renin hypertensives can be sub-classified according to their most effective diuretic;
2. Whether this sub-classification helps us to identify the genes and mutations responsible, since these are to expected to be in the so-called sodium channels (i.e. salt pumps)which the kidneys use to prevent salt being excreted in the urine.

Inclusion Criteria:

• Aged 18-45
• male or female
• Hypertensive - 3 clinic SBP >=140mmHg; or 3 clinic DBP >=90mmHg; or ABPM or home BP >=130(SBP) or 85(DBP)
• 24hr Na+<160mmol/l
• EITHER {Plasma renin<=10mU/L (measured untreated, or whilst receiving only CCB+/-diuretic} + {Plasma renin <=40mU/L (measured on an ACEi or ARB, which approximately double s the plasma renin)} OR Plasma renin <5mU/L (measured untreated, or receiving any antihypertensive drug other than a beta-blocker

Exclusion Criteria:

• Documented history of gout
• Abnormal renal function (both elevated serum creatinine and reduced creatinine clearance
• SBP > 170mmHg or Diastolic >110mmHg despite treatment with permitted background treatment