Explorative Study to Investigate the Acid-base Response to Sodium and Potassium Salts in Patients With Chronic Kidney Disease. (5S)

With this research the investigators want to study how patients with chronic kidney disease respond to different sodium- and potassium salts. Potassium salts can prevent kidney damage and cardiovascular disease, however patients with chronic kidney disease can responds differently. Extra potassium can increase the amount of potassium in the blood and extra chloride can cause acidosis. With this study the investigators will gain more insight in how patients with chronic kidney disease respond to sodium and potassium salts and which one is more favorable.This information can then be used to guide the application of salt substitutes and dietary adjustments in patients with chronic kidney disease.

Study Overview

• Status: Active, not recruiting
• Conditions: CKD; Electrolyte and Fluid Balance Conditions; Metabolic Acidosis
• Intervention / Treatment: Dietary supplement: Dietary supplement consisting of 40 mmol/daily of sodium chloride; Dietary supplement: Dietary supplement consisting of 40 mmol/daily of sodium bicarbonate; Dietary supplement: Dietary supplement consisting of 40 mmol/daily of potassium chloride; Dietary supplement: Dietary supplement consisting of 40 mmol/daily of potassium bicarbonate; Dietary supplement: Dietary supplement consisting of 40 mmol/daily of potassium gluconate; Dietary supplement: Placebo caps

Detailed Description

Rationale: Patients with chronic kidney disease (CKD) consume a low potassium diet which is associated with progressive CKD and cardiovascular disease. Increasing dietary potassium intake to recommended levels may therefore improve cardiorenal outcomes, but the response to increased potassium intake in patients with CKD is unclear. Therefore, the investigators recently tested the response to 40 mmol potassium chloride in patients with CKD and showed that this is generally well-tolerated. However, patients did develop mild hyperchloremic metabolic acidosis, which may offset the beneficial effects of potassium. The investigators hypothesize that this is a form of chloride-induced acidosis that may be prevented by giving potassium with a different anion than chloride. To further investigate this, the investigators propose to test the response to five different sodium and potassium salts in patients with CKD. These results should inform us on how to best correct a potassium-deficient diet in patients with CKD.

Objective: To test the effects of five different sodium and potassium salts in patients with CKD.

Study design: Investigator-initiated, single-center, placebo-controlled double-blind randomized crossover study.

Study population: Adult outpatients (age ≥ 18 years) with CKD stage G3b or G4 using renin-angiotensin-aldosterone system inhibitors (RAAS-I).

Intervention: Capsules with 40 mmol potassium chloride, potassium bicarbonate, potassium gluconate, sodium bicarbonate, sodium chloride or placebo (3 x 3 capsules per day).

Main study parameters/endpoints: Difference in plasma bicarbonate after treatment.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The study lasts 6 weeks and consists of 7 visits that will consist of blood sampling, 24-hour urine collection and spot urine collection. We will also provide an automated blood pressure measuring device for at home blood pressure measurements. Although these procedures are time-consuming and may be experienced as burdensome, they are all routine clinical measurements and safe. Patients may experience a pill-burden. The two risks of the salt supplements are hyperkalemia (with potassium salts) and hypertension (with sodium salts). Based on our previous studies a minority of patients is expected to develop these side-effects (< 12%). Safety measures to prevent, monitor and treat these side-effects are included in the study protocol. There are no direct benefits for patients participating in this trial, but the results will contribute to a better understanding on the feasibility of dietary modifications and salt substitution in patients with CKD to improve health. Patients will be reimbursed for their participation.

• Study Type: Interventional
• Enrollment (Estimated): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • ErasmusMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (≥ 18 years)
• CKD G3b or G4 (44 - 15 ml/min/1.73 m2)
• Use of RAAS-I (ACE-inhibitor or angiotensin receptor blocker, ARB)

Exclusion Criteria:

• Use of any of the following drugs or supplements: mineralocorticoid receptor antagonists, potassium-sparing diuretics, oral potassium binders, immunosuppressive medication, tolvaptan, acetazolamide, topiramate, sodium bicarbonate.
• Patients using double RAAS blockade (i.e., ACE-inhibitor + ARB).
• Metabolic alkalosis (plasma bicarbonate >27 mmol/L) at last outpatient visit
• Kidney transplant recipients
• Patients with an active gastro-intestinal ulcer
• Patients with previous history of ventricular cardiac arrhythmia
• Patients with a life expectancy < 6 months
• Incapacitated subjects or subjects who are deemed unfit to adequately adhere to instructions from the research team
• Women who are pregnant, breastfeeding or consider pregnancy in the coming 7 weeks
• Patients with chronic respiratory acidosis in previous medical history
• Hyperkalemia (plasma potassium >5.5 mmol/L) at V0

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Placebo caps; The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.
Active Comparator: Sodium chloride; 40 mmol of oral sodium chloride daily for 5 days	Dietary supplement: Dietary supplement consisting of 40 mmol/daily of sodium chloride; The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.
Active Comparator: Sodium bicarbonate; 40 mmol of oral sodium bicarbonate daily for 5 days	Dietary supplement: Dietary supplement consisting of 40 mmol/daily of sodium bicarbonate; The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.
Active Comparator: Potassium chloride; 40 mmol of oral potassium chloride daily for 5 days	Dietary supplement: Dietary supplement consisting of 40 mmol/daily of potassium chloride; The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.
Active Comparator: Potassium bicarbonate; 40 mmol of oral potassium bicarbonate daily for 5 days	Dietary supplement: Dietary supplement consisting of 40 mmol/daily of potassium bicarbonate; The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.
Active Comparator: Potassium gluconate; 40 mmol of oral potassium gluconate daily for 5 days	Dietary supplement: Dietary supplement consisting of 40 mmol/daily of potassium gluconate; The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma bicarbonate by blood draw	The absolute difference per treatment group in measured plasma bicarbonate after treatment. After each treatment of 5 days, plasma bicarbonate will be measured by blood sampling. The difference between the groups (treatments) will be the main outcome and comparator.	After 5 days of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma electrolyte levels	Na, Cl, K, Mg, Ca, Phosphate (all in mmol/L)	After 5 days of intervention
Urinary citrate	Urinary citrate in mmol/24h	After 5 days of intervention
Urinary ammonia	urinary ammonia in mmol/24, calculated using the Berthelot method	After 5 days of intervention
Titratable acid	Titratable acid = (0.067) × (mLs NaOH (sample titration) - mLs NaOH (blank titration)) × 75/ mLs of sample	After 5 days of intervention
Net acid excretion	Net acid excretion unit/24h, formula = sum of the titratable acid and concentration of ammonia minus the concentration of bicarbonate.	After 5 days of intervention
Potential renal acid load	PRAL (mEq/d) = 0.49 × protein (g/d) + 0.037 × phosphate (mg/d) - 0.021 × potassium (mg/d) - 0.026 × magnesium (mg/d) - 0.013 × calcium (mg/d).	After 5 days of intervention
Body weight	Weight measured by a scale in kilograms	After 5 days of intervention
Blood pressure	Systolic and diastolic blood pressure measured 2 times daily during the study, so 20 times during the 5 days of supplement usage. Measurements will be done in the morning and evening measured twice in seated position with an automatic blood pressure monitor.	2 measurements in the morning and evening for 5 days per treatment repeated for 6 treatments in total

Collaborators and Investigators

• Sponsor: Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2024
• Primary Completion (Actual): March 21, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: July 25, 2023
• First Submitted That Met QC Criteria: January 25, 2024
• First Posted (Actual): February 1, 2024

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 7, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Renal Insufficiency; Acid-Base Imbalance; Kidney Diseases; Renal Insufficiency, Chronic; Acidosis
• Other Study ID Numbers: NL84462.078.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No