The Role of Skin Sodium Accumulation in Chronic Kidney Disease

Inclusion Criteria: 1. Chronic kidney disease with an eGFR between 15 and 60 ml/min/1.73m2. 2. Stable diuretic and antihypertensive treatment for the previous 6 weeks. Additional inclusion criteria for the sodium excretion intervention 1. Office systolic blood pressure (SBP) \>135 mmHg Additional inclusion criteria for the water intervention 1. Chronic kidney disease with an eGFR between 15 and 29 ml/min/1.73m2 2. Office blood pressure ≥140/90 mmHg or use of antihypertensive medication 3. Fasting morning urine osmolality \<425 mOsm/kg for men and \< 400 mOsm/kg for women Exclusion Criteria: 1. Age \<18 years. 2. The patient is expected to start renal replacement therapy or is planned to receive a kidney transplantation within 3 months. 3. An active diagnosis of nephrotic syndrome at inclusion. 4. (Recurrent) acute glomerulonephritis within 1 year prior to the study. 5. Salt losing nephropathy. 6. Use of oral or intravenous glucocorticoids with an equivalent of prednisolone \>5mg/day. 7. Contra-indication for MRI. 8. Cardiovascular event/ surgery in the previous 3 months. 9. Pregnant women, women of child bearing age planning to conceive for the study duration, women of child bearing age without contraception. 10. Participation in other (pharmacological) intervention studies. 11. Presence of significant comorbidities with a life expectancy of less than 1 year. 12. Disorder that compromises the participants' ability to give truly informed consent for participation in this study. 13. Patients with an active infection and/or auto-immune diseases with involvement of the lower extremities. 14. Any other issues that in opinion of the investigator could be harmful to the subject or compromise interpretation of the data. Additional exclusion criteria for the sodium intake intervention 1\. Chronic use of NSAID Additional exclusion criteria for the sodium excretion intervention 1. Serum potassium concentration \>5.0 mmol/l. 2. eGFR \<30 ml/min/1.73m2 3. Uncontrolled hypertension (\>180/100 mmHg) 4. Severe heart failure with left ventricular ejection fraction \<30%. 5. Contra-indication for investigational drugs. 6. Severe symptoms of (orthostatic) hypotension. 7. Patients with obstruction of the outflow tract of the left ventricle such as aortic valve stenosis. 8. Refractory hypokalemia, hyponatremia or hypercalcemia. 9. Severe liver insufficiency Child Pugh B/C 10. Chronic use of NSAID. Additional exclusion criteria for the water intake intervention 1. Recent history of severe hyponatremia (outpatient plasma sodium \< 130 mmol/L in the last 6 months) 2. Plasma sodium \<135 mmol/L at screening 3. History of heart failure 4. Use of lithium, vasopressin analoga, vasopressin antagonists, oral or intravenous glucocorticoids, thiazide diuretics. 5. 24-hour urine volume \> 2L 6. Chronic use of NSAID