Potassium Supplementation in CKD (K+ in CKD)

Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease (CKD)

The current high-sodium, low-potassium diet contributes to the high prevalence of high blood pressure (hypertension). Indeed, the anti-hypertensive effects of potassium supplementation are well-established. Hypertension is even more prevalent and resistant in patients with chronic kidney disease (CKD) and contributes to further decline in kidney function. Four recent epidemiological studies (published 2014 - 2016) showed that higher dietary potassium intake was associated with better renal outcomes. All studies recommended an intervention study with potassium supplementation in patients with CKD, but this has not been performed. The aim of this study is to study the renoprotective effect of potassium supplementation in patients with CKD (stage 3b or 4, i.e. estimated glomerular filtration rate [eGFR] 15 - 45 ml/min/1.73 m2).

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertension; Renal Insufficiency, Chronic; Hyperkalemia; Potassium Depletion
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Potassium Chloride; Dietary supplement: Potassium Citrate

• Study Type: Interventional
• Enrollment (Estimated): 532
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center Amsterdam
  • Groningen, Netherlands
    • University Medical Center Groningen
  • Leiden, Netherlands
    • Leiden University Medical Center
  • Rotterdam, Netherlands
    • Erasmus MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• CKD 3b or 4 (45 - 15 ml/min/1.73 m2)
• Δ eGFR (as estimated by the CKD-EPI equation) > 2 ml/min/1.73 m2/year (in preceding ≥ 1 year with at least 3 measurements)
• Hypertension (defined as office blood pressure > 140/90 mmHg or use of anti-hypertensive medication)

Exclusion Criteria:

• Hyperkalemia (serum potassium > 5.5 mmol/l) at study visit V0
• Medical reasons to continue dual RAAS-blockade, mineralocorticoid receptor blockers, potassium-sparing diuretics, or oral potassium binders.
• Patients with previous history of ventricular cardiac arrhythmia
• Patients with a life expectancy < 6 months
• Expected initiation of renal replacement therapy < 2 years
• Incapacitated subjects
• Women who are pregnant, breastfeeding or consider pregnancy in the coming 2 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Placebo; Placebo
Experimental: Potassium Chloride; Experimental Arm 1 - Rationale is that most evidence for a positive effect of potassium comes from studies using potassium chloride	Dietary supplement: Potassium Chloride; Two potassium supplements with varying anions.
Experimental: Potassium Citrate; Experimental Arm 2 - Rationale for citrate is that recent evidence indicates that alkali treatment may also be renoprotective.	Dietary supplement: Potassium Citrate; Potassium Citrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference in estimated glomerular filtration rate (eGFR)	Two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
≥ 30% decrease in eGFR		Two years
Slope analysis (change in eGFR in ml/min/1.73 m2/year)		Two years
Doubling in serum creatinine or end-stage renal disease		Two years
Progression to next CKD or albuminuria class		Two years
Ambulatory (24-hour) blood pressure		Two years
24-hour albuminuria		Two years
Cardiovascular event	Coronary heart disease death, fatal myocardial infarction, fatal stroke and other cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, resuscitated cardiac arrest	Two years
All-cause mortality		Two years
Incidence of hyperkalemia		Two years
NT-pro-BNP	Volume marker 1	Two years
Bioimpedance measures	Volume marker 2	Two years
Pulse-wave velocity	Cardiovascular marker 1	Two years
High-sensitive CRP	Cardiovascular marker 2	Two years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of 2-week KCl supplementation on plasma potassium (mmol/l)	Run-in outcome 1	Two weeks
Incidence of Hyperkalemia after 2-week KCl supplementation	Run-in outcome 2	Two weeks
Effects of 2-week KCl supplementation on office blood pressure (mmHg)	Run-in outcome 3	Two weeks

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: University Medical Center Groningen; Leiden University Medical Center; Dutch Kidney Foundation; Amsterdam UMC
• Investigators: Principal Investigator: Ewout J Hoorn, MD, PhD, Erasmus Medical Center

Publications and helpful links

General Publications

• Gritter M, Wouda RD, Yeung SMH, Wieers MLA, Geurts F, de Ridder MAJ, Ramakers CRB, Vogt L, de Borst MH, Rotmans JI, Hoorn EJ; on behalf of K onsortium. Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD. J Am Soc Nephrol. 2022 Sep;33(9):1779-1789. doi: 10.1681/ASN.2022020147. Epub 2022 May 24.
• Sunga CGG, Zelnick LR, Bansal N. Urinary Sodium and Potassium Excretion and the Risk of Cardiovascular Events in CKD. Kidney360. 2026 Jan 1;7(1):94-106. doi: 10.34067/KID.0000000943. Epub 2025 Aug 8. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: August 15, 2017
• First Submitted That Met QC Criteria: August 16, 2017
• First Posted (Actual): August 17, 2017

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Renal Insufficiency; Water-Electrolyte Imbalance; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Hypertension; Renal Insufficiency, Chronic; Hyperkalemia; Hypokalemia; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Inorganic Chemicals; Chlorine Compounds; Chlorides; Hydrochloric Acid; Citrates; Tricarboxylic Acids; Citric Acid; Potassium Compounds; Potassium Citrate; Potassium Chloride
• Other Study ID Numbers: NL60825.078.17; MEC-2017-226 (Other Identifier: ErasmusMC); CP16.01 (Other Grant/Funding Number: Dutch Kidney Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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