The Role of Skin Sodium Accumulation in Chronic Kidney Disease

Prior treatment

• The patient is expected to start renal replacement therapy or is planned to receive a kidney transplantation within 3 months.
• (Recurrent) acute glomerulonephritis within 1 year prior to the study.
• Cardiovascular event/ surgery in the previous 3 months.
• Contra-indication for investigational drugs.

Other illness

• An active diagnosis of nephrotic syndrome at inclusion.
• Disorder that compromises the participants' ability to give truly informed consent for participation in this study.
• Patients with an active infection and/or auto-immune diseases with involvement of the lower extremities.
• Uncontrolled hypertension (\>180/100 mmHg)
• Severe liver insufficiency Child Pugh B/C
• History of heart failure

Lab values

• 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
• Serum potassium concentration \>5.0 mmol/l.
• eGFR \<30 ml/min/1.73m2
• Severe heart failure with left ventricular ejection fraction \<30%.
• Recent history of severe hyponatremia (outpatient plasma sodium \< 130 mmol/L in the last 6 months)
• Plasma sodium \<135 mmol/L at screening

Age

• Age \<18 years.
• Pregnant women, women of child bearing age planning to conceive for the study duration, women of child bearing age without contraception.

Other

• Salt losing nephropathy.
• Use of oral or intravenous glucocorticoids with an equivalent of prednisolone \>5mg/day.
• Contra-indication for MRI.
• Participation in other (pharmacological) intervention studies.
• Presence of significant comorbidities with a life expectancy of less than 1 year.
• Severe symptoms of (orthostatic) hypotension.
• Patients with obstruction of the outflow tract of the left ventricle such as aortic valve stenosis.
• Refractory hypokalemia, hyponatremia or hypercalcemia.
• Chronic use of NSAID.
  • Additional exclusion criteria for the water intake intervention
• Use of lithium, vasopressin analoga, vasopressin antagonists, oral or intravenous glucocorticoids, thiazide diuretics.
• 24-hour urine volume \> 2L
• Chronic use of NSAID

• Chronic kidney disease with an eGFR between 15 and 60 ml/min/1.73m2.
• 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
• Chronic kidney disease with an eGFR between 15 and 29 ml/min/1.73m2
• Office blood pressure ≥140/90 mmHg or use of antihypertensive medication
• Fasting morning urine osmolality \<425 mOsm/kg for men and \< 400 mOsm/kg for women