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Nephron. 2018;140(1):48-57. doi: 10.1159/000490261. Epub 2018 Jun 29.

Rationale and Design of a Randomized Placebo-Controlled Clinical Trial Assessing the Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease.

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Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Internal Medicine, Division of Nephrology, Academic Medical Center, Amsterdam, the Netherlands.
Department of Nephrology, University Medical Center Groningen, Groningen, the Netherlands.
Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Internal Medicine, Nephrology, Leiden University Medical Center, Leiden, the Netherlands.



Dietary potassium (K+) has beneficial effects on blood pressure and cardiovascular (CV) outcomes. Recently, several epidemiological studies have revealed an association between urinary K+ excretion (as proxy for dietary intake) and better renal outcomes in subjects with chronic kidney disease (CKD). To address causality, we designed the "K+ in CKD" study.


The K+ in CKD study is a multicenter, randomized, double blind, placebo-controlled clinical trial aiming to include 399 patients with hypertension, CKD stage 3b or 4 (estimated glomerular filtration rate [eGFR] 15-44 mL/min/1.73 m2), and an average eGFR decline > 2 mL/min/1.73 m2/year. As safety measure, all included subjects will start with a 2-week open-label phase of 40 mmol potassium chloride daily. Patients who do not subsequently develop hyperkalemia (defined as serum K+ >5.5 mmol/L) will be randomized to receive potassium chloride, potassium citrate (both K+ 40 mmol/day), or placebo for 2 years. The primary end point is the difference in eGFR after 2 years of treatment. Secondary end points include other renal outcomes (> 30% decrease in eGFR, doubling of serum creatinine, end-stage renal disease, albuminuria), ambulatory blood pressure, CV events, all-cause mortality, and incidence of hyperkalemia. Several measurements will be performed to analyze the effects of potassium supplementation, including body composition monitoring, pulse wave velocity, plasma renin and aldosterone concentrations, urinary ammonium, and intracellular K+ concentrations.


The K+ in CKD study will demonstrate if K+ sup-plementation has a renoprotective effect in progressive CKD, and whether alkali therapy has additional beneficial effects.


Albuminuria; Alkali; Cardiovascular disease; Citrate; Hypertension

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