Safety of a Healthy Plant-based Diet With Higher Potassium Content, Compared to a Healthy Plant-based Diet With Limited Potassium Content in Patients With Chronic Kidney Disease: A Pilot Study

Официальное название

Säkerheten av en hälsosam växtbaserad Kost Med högre kaliuminnerhåll, jämfört Med en hälsosam växtbaserad Kost Med begränsat kaliuminnehåll Hos Patienter Med Kronisk Njursjukdom: En Pilotstudie

Обзор

For many years, people with moderate to advanced chronic kidney disease (CKD) have been advised to limit their intake of potassium, a mineral found in many foods such as fruit, vegetables, legumes, whole grains, and nuts. The reason for this has been the risk of hyperkalemia, a condition in which the potassium level in the blood becomes too high and can be dangerous. In recent years, however, this view has been questioned. New research suggests that the link between potassium in food and high potassium levels in the blood may not be as clear as previously thought. People who follow a strict potassium-restricted diet experience a lower quality of life and less satisfaction with their dietary treatment. At the same time, they miss out on the health benefits of eating a varied and nutritious diet. Today, many experts advocate a more individualized approach to potassium intake: instead of generally restricting potassium, the goal should be to maintain normal potassium levels in the blood, while encouraging a healthy diet. However, this message is not always clear in healthcare, and many people therefore continue to avoid potassium-rich foods altogether. The result is that they eat fewer natural ingredients and instead consume more processed and ultra-processed foods. Such foods can be more harmful, partly because they often contain potassium additives that are absorbed effectively by the body and their quantities are not reported in the nutritional label. This "hidden" potassium can contribute more to high potassium levels in the blood than the potassium that occurs naturally in plant-based foods. In addition, potassium from whole plant-based foods is absorbed more slowly, partly due to its fiber content. Plant-based diets may also have other positive effects for people with kidney disease: they can contribute to reduced blood acidity, known as metabolic acidosis, healthier gut flora, lower levels of inflammation, and reduced phosphorus intake. Together, these factors can counteract several of the metabolic complications associated with kidney disease. In a previous study, our research group showed that even patients with advanced kidney disease (CKD stage 4-5) and already elevated potassium levels could follow a healthy plant-based diet if they also used a potassium-binding drug (sodium zirconium cyclosilicate, SZC). This enabled them to eat more fruit, vegetables, and legumes, while also experiencing improved quality of life. The current study builds on these results and is planned as a pilot study in which patients with moderate to advanced kidney disease, but who are not yet being treated with dialysis, are assigned to two different dietary strategies for six months: * Healthy plant-based diet (healthy-PBD): a more liberal and balanced plant-based diet without specific potassium restrictions. * Potassium-restricted plant-based diet (restricted-PBD): a traditional plant-based diet with restrictions on potassium-rich foods, according to current standard recommendations. The main purpose is to investigate whether the healthy plant-based diet leads to more or more severe cases of hyperkalemia than the restricted diet. Our hypothesis is that potassium levels may increase slightly in the group with a liberal diet, but not to dangerous levels. The study will also examine secondary outcomes, such as quality of life, satisfaction with treatment, and how well patients accept the diet. In addition, taste experiences will be tested with taste strips (sweet, sour, salt, bitter and umami) before and after the intervention in both groups. If this pilot study shows that a healthier and less restrictive diet is safe, it could pave the way for a larger study investigating the long-term metabolic effects of a plant-based diet in kidney care.

Подробное описание

The overall aim of the project is to investigate whether a liberal plant-based diet, rich in fruit, vegetables, legumes, whole grains, and nuts, can be recommended to patients with mild to advanced kidney disease without leading to hyperkalemia. Traditionally, dietary advice for chronic kidney disease (CKD) has focused on potassium restriction, which has led to reduced intake of healthy foods and thereby poorer diet quality. This project aims to challenge this view by shifting the focus from potassium content itself to overall diet quality, with a particular focus on patient-centered outcomes such as safety, quality of life, treatment satisfaction, acceptance and sensory effects (taste sensitivity).

The study addresses an important knowledge gap in current nutritional guidelines for patients with kidney disease. The latest recommendations emphasize individualization and maintaining normal potassium levels, rather than general restrictions, but this advice is based on limited evidence and has not yet been tested in longer clinical studies.

This project is therefore limited to conducting a 6-month pilot study with a randomized controlled design. The focus is primarily on safety outcomes, especially the occurrence of hyperkalemia, and secondarily on patient-reported outcomes, dietary acceptance, and taste experience. Metabolic effects are not examined in detail in this study, but the results will form the basis for a larger follow-up study with a broader focus on long-term metabolic and clinical benefits.

The project's main scientific question is whether it is safe for patients with moderate to advanced kidney disease to eat a plant-based diet without restricting potassium-rich foods. In current clinical practice, patients are advised to avoid fruits, vegetables, legumes, and nuts, despite the fact that an increasing number of studies suggest that potassium from whole plant-based foods does not necessarily lead to dangerously high potassium levels in the blood. The study defines the following outcome measures:

Primary outcome: Time to first hyperkalemia event (plasma potassium \> 5.5 mmol/L). Number of hyperkalemia events in the two groups during the 22-26 weeks following randomization. Potassium as a continuous variable.

Secondary endpoints: Patient-reported endpoints, quality of life (RAND-36 questionnaire) and satisfaction with treatment. Laboratory markers: inflammation, kidney function, acid-base balance, uremic toxins, vitamin K, and gut flora-related markers. Nutrition-related factors: body composition (measured using bioelectrical impedance), anthropometry, dietary intake, and taste test (sweet, sour, salt, bitter and umami). Dietary compliance: structured questionnaire on intake and 24-hour urine collection for potassium excretion.

This study is designed as a pilot study with a parallel randomized controlled trial (RCT) design with a duration of 22-26 weeks (approximately 6 months). The study will include adult participants (age 20-85) with moderate to advanced CKD, defined as estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m², who are not yet being treated with dialysis nor have undergone kidney transplantation. Individuals with untreated comorbidities or conditions that may affect study participation will be excluded.

Randomization and intervention

Participants will be randomly assigned in a 1:1 ratio to one of two groups:

* Healthy plant-based diet (healthy-PBD): A liberal plant-based diet that includes fruits, vegetables, legumes, whole grains, and nuts, with no specific restrictions on potassium. * Potassium-restricted plant-based diet (restricted-PBD): A plant-based diet with restrictions on potassium-rich foods, which corresponds to current standard advice for patients with CKD.

Both groups will receive individually tailored dietary counselling from a dietitian at baseline and during follow-up visits. Counselling will cover portion sizes, meal composition, and strategies for adhering to the assigned diet. Participants will also receive written dietary advice and food lists.

Study procedures and visits Participants will attend study visits at baseline, 4 weeks, 12 weeks, and 22-26 weeks. The following will be performed at each visit:

* Blood tests: plasma potassium (primary safety measure), kidney function (creatinine, eGFR), acid-base balance, inflammation markers, vitamin K and uremic toxins. * Urine test: 24-hour urine collection for potassium, sodium, urea, and creatinine to assess compliance with the diet. * Anthropometry and body composition: weight, body mass index (BMI) and bioelectrical impedance analysis. * Patient-reported outcomes: quality of life (RAND-36) and questionnaire on satisfaction with treatment. * Sensory tests: taste strips to assess thresholds for sweet, sour, salt, bitter and umami. * Diet compliance: structured dietary questionnaire focusing on plant-based foods and potassium-rich foods, as well as a 24-hour record about intake.

Participants are instructed to contact the study team if they experience symptoms that may indicate hyperkalemia, such as muscle weakness or palpitations. If hyperkalemia (p-potassium \> 5.5 mmol/L) is detected, adequate medical treatment will be provided, and continued participation in the study will be reconsidered for safety reasons.

Data collection All laboratory analyses will be performed at accredited hospital laboratories according to standardized methods with internal and external quality control. Dietary questionnaires will be validated against urinary potassium excretion. Quality of life and satisfaction questionnaires are validated versions in Swedish. Taste strips will be used under standardized conditions.

To ensure data reliability, all study data will be collected by personnel trained in standardized procedures. Randomization will be computer-generated with concealed allocation. Data entry will be double-checked and deviations verified against source material.

Surveys and interviews The structured dietary surveys will include questions about the frequency and portion size of selected food groups, adherence to prescribed portions, and barriers to following the diet. The survey on treatment satisfaction will include questions about perceived safety, trust in dietary advice, and willingness to continue with the diet after the end of the study. The responses will be analyzed descriptively and compared between groups to identify differences in acceptance and adherence.

Time commitment for participants Each study visit is expected to take approximately 60-90 minutes and will include blood and urine sampling, anthropometry, surveys, and dietary counselling. Participants will also be asked to fill in the dietary records at home and collect 24-hour urine samples at predetermined time points.

The entire study will be conducted in Sweden. All recruitment, intervention, laboratory analyses and follow-up will take place at participating Swedish nephrology clinics.

Вмешательства

• Другое Healthy plant-based diet (healthy-PBD)
  Healthy plant-based diet (healthy-PBD): A liberal plant-based diet that includes fruits, vegetables, legumes, whole grains, and nuts, with no specific restrictions on potassium.
• Другое Potassium-restricted plant-based diet
  Potassium-restricted plant-based diet (restricted-PBD): A plant-based diet with restrictions on potassium-rich foods, which corresponds to current standard advice for patients with CKD.

Первичные конечные точки

• Number of hyperkalemia (plasma potassium >5.5 mmol/L) events in the two groups [Срок оценки: for 26 weeks following randomization]

Вторичные конечные точки (12)

• Quality of life (RAND-36 questionnaire - score 0 to 100) [Срок оценки: for 26 weeks following randomization]
• Renal Treatment Satisfaction Questionnaire - score 0 to 6 [Срок оценки: for 26 weeks following randomization]
• C-reactive protein (mg/L) [Срок оценки: for 26 weeks following randomization]
• Interleukin 6 (pg/mL) [Срок оценки: for 26 weeks following randomization]
• Glomerular filtration rate (ml/min/1.73 m2) [Срок оценки: for 26 weeks following randomization]
• Albumin/creatinine ratio (spot urine) (mg/g) [Срок оценки: for 26 weeks following randomization]
• 24-hour urinary creatinine excretion (mg/L) [Срок оценки: for 26 weeks following randomization]
• Serum creatinine (µmol/L) [Срок оценки: for 26 weeks following randomization]
• Plasma carbon dioxide (mmol/L) [Срок оценки: for 26 weeks following randomization]
• Plasma Trimethylamine N-oxide (TMAO) (ng/mL) [Срок оценки: for 26 weeks following randomization]
• Plasma p-Cresyl sulfate (ng/mL) [Срок оценки: for 26 weeks following randomization]
• Plasma Indoxyl sulfate (ng/mL) [Срок оценки: for 26 weeks following randomization]

Критерии участия

Критерии включения

• Age between 20 and 85 years
• Chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²
• Normal potassium levels (plasma potassium 3.5-5.3 mmol/L)
• Not on dialysis
• Good knowledge of Swedish

Критерии исключения

• Pregnancy
• Breastfeeding
• Kidney transplant
• Regular use of potassium binders at least 4 days/week (e.g. sodium zirconium cyclosilicate, patiromer or sodium polystyrene sulfonate)
• Regular prescription of daily potassium salts (e.g. potassium chloride)
• Planned kidney transplant
• Planned start of dialysis within the next 6 months
• Allergy to nuts (including peanuts)
• Mental illness and cognitive impairment that impede understanding of dietary advice
• Comorbidities that may affect potassium balance (e.g. adrenal insufficiency, inflammatory bowel disease, chronic diarrhoea or colostomy)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Швеция · 1 центр

• Karolinska Institute — Huddinge

Публикации

• 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. PMID 35609996
• Morris A, Krishnan N, Kimani PK, Lycett D. Effect of Dietary Potassium Restriction on Serum Potassium, Disease Progression, and Mortality in Chronic Kidney Disease: A Systematic Review and Meta-Analysis. J Ren Nutr. 2020 Jul;30(4):276-285. doi: 10.1053/j.jrn.2019.09.009. Epub 2019 Nov 14. PMID 31734057
• Clase CM, Carrero JJ, Ellison DH, Grams ME, Hemmelgarn BR, Jardine MJ, Kovesdy CP, Kline GA, Lindner G, Obrador GT, Palmer BF, Cheung M, Wheeler DC, Winkelmayer WC, Pecoits-Filho R; Conference Participants. Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2020 Jan;97(1): PMID 31706619
• GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020 Feb 29;395(10225):709-733. doi: 10.1016/S0140-6736(20)30045-3. Epub 2020 Feb 13. PMID 32061315
• Turban S, Juraschek SP, Miller ER 3rd, Anderson CAM, White K, Charleston J, Appel LJ. Randomized Trial on the Effects of Dietary Potassium on Blood Pressure and Serum Potassium Levels in Adults with Chronic Kidney Disease. Nutrients. 2021 Jul 31;13(8):2678. doi: 10.3390/nu13082678. PMID 34444838
• Inker LA, Grams ME, Levey AS, Coresh J, Cirillo M, Collins JF, Gansevoort RT, Gutierrez OM, Hamano T, Heine GH, Ishikawa S, Jee SH, Kronenberg F, Landray MJ, Miura K, Nadkarni GN, Peralta CA, Rothenbacher D, Schaeffner E, Sedaghat S, Shlipak MG, Zhang L, van Zuilen AD, Hallan SI, Kovesdy CP, Woodward M, Levin A; CKD Prognosis Consortium. Relationship of Estimated GFR and Albuminuria to Concurrent PMID 30348535
• Hansen NM, Berg P, Rix M, Pareek M, Leipziger J, Kamper AL, Astrup A, Vaarby Sorensen M, Salomo L. The New Nordic Renal Diet Induces a Pronounced Reduction of Urine Acid Excretion and Uremic Toxins in Chronic Kidney Disease Patients (Stage 3 and 4). J Ren Nutr. 2023 May;33(3):412-419. doi: 10.1053/j.jrn.2022.09.010. Epub 2022 Oct 3. PMID 36195272
• Dos Santos RG, Scatone NK, Malinovski J, Sczip AC, de Oliveira JC, Morais JG, Ramos CI, Nerbass FB. Higher Frequency of Fruit Intake Is Associated With a Lower Risk of Constipation in Hemodialysis Patients: A Multicenter Study. J Ren Nutr. 2021 Jan;31(1):85-89. doi: 10.1053/j.jrn.2020.07.004. Epub 2020 Aug 27. PMID 32863164

Идентификаторы

NCT: NCT07494266 · 2025-06661-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗