In this clinical study the anti-hypertensive response to dietary salt restriction is compared with the anti-hypertensive response to the diuretics hydrochlorothiazide/amiloride in adult patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are exquisitely salt-sensitive. Salt-sensitivity in CKD is linked to hypertension and cardiovascular outcomes. Dietary salt restriction is an accepted intervention for salt-sensitivity in CKD. Another strategy, however, could be to block sodium uptake by the kidney pharmacologically by diuretics. Especially diuretics acting on the distal tubule may be effective, because this appears to be the site of increased sodium reabsorption in CKD. It is currently unknown how these two strategies, diet or diuretics, relate. The investigators hypothesize that diuretics are non-inferior to diet.

Inclusion Criteria:

• Age > 18 years.
• CKD stage 3 or 4 (MDRD-GFR 15-60 ml/min)
• Use of any anti-hypertensive drugs
• No anti-hypertensive drugs but an average office systolic blood pressure > 140 mmHg (as measured by datascope)

Exclusion Criteria:

• Salt-wasting CKD
• Nephrotic syndrome
• Pregnant or breastfeeding women
• Life expectancy < 6 months
• Severe heart failure (NYHA III or IV) or liver cirrhosis with ascites and the inability to withdraw diuretics
• Rapidly declining kidney function with high likelihood of dialysis or kidney transplantation in the coming 4 months
• Kidney transplant recipients
• Use of immunosuppressive drugs
• Use of non-steroidal anti-inflammatory drugs
• Previous intolerance or allergy to hydrochlorothiazide or amiloride
• Serum sodium < 135 mmol/l
• Serum potassium < 3.5 mmol/l or > 5.0 mmol/l
• Inability to adhere to the study protocol (due to language, incapacitated subjects, subjects with intellectual disability)