Potassium Supplementation in CKD

Study Overview
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Brief Summary
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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).

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

Conditions
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Renal Insufficiency, Chronic, Potassium Depletion, Hypertension, Hyperkalemia

Intervention / Treatment
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* Dietary Supplement: Potassium Chloride
* Dietary Supplement: Potassium Citrate
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |