Ongoing studies at Food as Medicine

The uremic milieu and the dialysis modalities (hemodialysis and peritoneal dialysis) leads to metabolic disturbances including an increased protein catabolism, an altered gut microbiota (dysbiosis) among others. The dietary restriction of foods rich in potassium (fruits, vegetables, grains, whole cereals and nuts) can further exacerbate dysbiosis and perpetuate a vicious cycle marked by unhealthy eating, comorbidities and worse overall health.

This is the theme of an ongoing interventional feasibility study - HELPFUL Study - where the aim is to test the role of shifting from a diet restricted in potassium to a healthy dietary pattern similar to a plant-based diet with increased amount of fruits, vegetables, legumes, whole cereals, nuts and limited servings of white meat, fish or eggs to CKD patients on stages 4-5 not on dialysis with hyperkalemia. The potassium lowering medication sodium zirconium cyclosilicate will be used concomitantly to normalize potassium levels. The primary outcome will be improving patients satisfaction to the treatment, uremic symptoms and adherence to the target energy and protein recommendations and the secondary outcome will be controlling plasma potassium, improving quality of life, ameliorating intestinal obstipation, maintain the dosage antihypertensives with blockade of renin-angiotensin-aldosterone system, diminishing inflammation, better control of phosphate and bicarbonate levels and leading to a more healthy microbiota. 

Researchers involved in the HELPFUL study

Peter Stenvinkel, Principal investigator 
Carla Maria Avesani
Pernilla Bollander,
Ulrika Jensen Durgé
Yvonne Ekelöw
Olof Heimburger
Charlotta Rubin
Torsten Sallstrom
Valeria Cecchini

Funding

Astra Zeneca

More information about the study

You can find more information at ClinicalTrials.gov where the study is registered

The glycemic control of patients with chronic kidney disease (CKD) with glomerular filtration rate (GFR) below 30 ml/min/1.73m² and type 2-DM is a challenge for many clinicians. Due to the risk of developing lactic acidosis, metformin  is contra-indicated as an oral hypoglycemic agent to this patient group. This reinforces the need to explore life style factors, such as those found in dietary compounds, as potential treatment for better glycemic control. 

 Under this concept, we are interested in testing broccoli sprout extract as a potential intervention in ameliorating glucose control in patients with CKD and type 2-DM with overweight and obesity and with GFR between 15-45 ml/min/1.73 m² . Broccoli sprout is known to have high concentration of glucoraphanin, the precursor of sulforaphane, which is as a natural activator of NRF2 signaling. This interventional study will be a multicenter randomized controlled trial including 120 patients followed for 20 weeks. In the first 12 weeks - treatment period – patients will be randomized to BSE (BSE group) or placebo (Control group) and the subsequent eight weeks, a observational period. The primary outcome will be amelioration in glycemic control (fasting plasma glucose and glycated hemoglobin) and secondary outcome will be amelioration liver steatosis, inflammation and oxidative stress. 

Researchers involved in the INITIATE study

Peter Stenvinkel, Principal investigator
Carla Maria Avesani
Marie Evans
Karolina Kublickiene
Oskar Swartling
Anders Rosengren
Alice Sabatino, and
"Nätverket för klinisk behandlingsforskning inom njurmedicin” 

• Anders Christensen,
• Anders Fernström, 
• Maria Eriksson Svensson
• Annette Bruchfeld
• Gregor Guron, 
• Mårten Segelmark, 
• Stefan Jacobsson, 
• Andreas Jonsson,
• Jon Johansson.

Funding

Vetenskapsrådet, 
Stig och Gunborg Westmans stiftelse för forskning, 
Martin Rind stiftelse. 

We aim to examine the acute effect of meal with increased amount of potassium on plasma potassium changes in adult patients with a GFR between 20 to 15 ml/min/1.73 m2 and normokalemia. 

A control group comprising adult healthy individuals will allow examining the effect of decreased kidney function on blood potassium measurements and to answer the following four questions:

1. In patients with normokalemia, what is the acute effect of a healthy meal with high-potassium content on blood potassium? 
2. In patients with normokalemia, what is the acute effect of an unhealthy meal with high-potassium content on blood potassium? 
3. What is the difference between the CKD patients and healthy adult individuals on the acute changes of blood potassium after a healthy meal with increased amount of potassium?
4. What is the difference between the CKD patients and healthy adult individuals on the acute changes of blood potassium after an unhealthy meal with increased amount of potassium?

The primary outcome will be changes in plasma potassium from baseline to 240 minutes, with serial measurements at 60, 120, 180 and 240 minutes. The time length of 4 hours was chosen considering a previous study showing that the circadian rhythm also plays a role in the variability of serum potassium, and that serum potassium in CKD patients is lower at 9pm and higher at 3pm and in healthy individuals lower at 9pm and higher at 1pm.

The novelty and clinical relevance that this project will bring is to better understand the impact that meals containing food with potassium additives have in increasing plasma potassium. This knowledge will add valuable information for clinicians to plan the diet of patients with CKD. This project will be started between October to December 2023, and we will use part of the grant for this application to finance the costs of this study. 

Researchers involved in the study

Carla Maria Avesani, Principal investigator
Peter Stenvinkel 
Bengt Lindholm
Alice Sabatino
Pernilla Bolander
Ulrika Jensen Durgé
Yvonne Ekelöw
Olof Heimburger
Valeria Cecchini

Funding

Stig och Gunborg Westmans stiftelse för forskning 

Malnutrition is present in 20-40 percent of patients on dialysis in Sweden. It is associated with poor outcomes, limits patient autonomy and worsens their quality of life. Hence, diagnosis of malnutrition is important to provide early treatment and ameliorate overall health. Despite this clear need, in clinical practice malnutrition is not routinely assessed with a standardized method. The “Global Leadership Initiative on Malnutrition Criteria (GLIM)” is an operational method recommended by the Swedish national association of dietitians for diagnosing malnutrition with tools available in clinics and hospitals. Hence, GLIM has the potential to become a new standard tool to enable screening and early diagnosis of DRM. 

We propose a study to examine the feasibility of including GLIM as part of the routine care in 8 dialysis clinics in Sweden. For that, there will be 3 study phases. 

Phase 1: Dietitians from seven dialysis clinics in Sweden will apply GLIM for 3 months in patients on dialysis. 

Phase 2: The results will be included in the newly created Nutrition section of the Svenskt Njurregister (SNR). 

Phase 3: The dietitians that participated in Phase 1 will join for 2 months structured focus meetings for qualitative assessment to investigate facilitators and barriers of implementing GLIM in the routine practice. We hope that the knowledge acquired in this project will lead to strategies applicable in clinical routine of dialysis centers in Sweden to screen and diagnose DRM to improve nutrition care. 

Researchers involved in this study

Carla Maria Avesani ,Principal investigator
Karin Windahl
Sintra Eyre
Linda Schiller
Ylva Orrevall
Tommy Cederholm
Bengt Lindholm
Alice Sabatino

Funding

Stiftelse för njursjuka 

Muscle derangements are frequently observed in patients with chronic kidney disease (CKD), specially in more advanced stages of the disease. Muscle derangements include loss of muscle mass and infiltration of ectopic adipose tissue (i.e. myosteatosis) within and in between muscle fibers.  Both the loss of muscle mass and the presence of myosteatosis result in reduced muscle strength, function, and exercise capacity. 

Studies investigating ways to reverse muscle loss and myosteatosis, while improving muscle function and strength have mainly focused on exercise and nutritional supplementation, with limited results. Recently, research on (-)- Epicatechin, an abundant flavanol present in cacao and green tea that structurally resemble 11‐β‐hydroxypregnenolone, a naturally occurring sterol involved in inducing mitochondrial biogenesi, showed an increase in skeletal muscle and exercise capacity both in experimental and clinical studies. 

The aim of the present cross-over pilot study is to evaluate the ability of (-)-Epicatechin to improve muscle myosteatosis and skeletal muscle functional capacity of 10 patients with advanced CKD. We hypothesize that 8 weeks of (-)- Epicatechin would improve imaging markers of myosteatosis and also improve markers of muscle function.

Researchers involved in this study

Alice Sabatino, Principal investigator
Peter Stenvinkel
Carla Maria Avesani
Karolina Kublickiene
Bengt Lindholm
Kristoffer Sola 
Torkel Brismar

End stage kidney disease (ESKD) is marked by important muscular abnormalities, meaning reduced muscle mass and quality, which is represented by the amount of force generated by unit of muscle mass. Many are the causes of such abnormalities, and those can be directly or indirectly related to ESKD, such as metabolic acidosis, insulin resistance, myosteatosis, disuse/inactivity, among others. Aging is also a cause of muscular abnormalities that is independent from ESKD. 

Research in other fields showed how the molecular mechanism directing the circadian rhytm, i.e. the circadian clock, can be influenced by metabolic derangements. The core clock genes include Bmal1, Clock, Rev-erba/β, Per and Cry, and they are responsible to regulate a daily program of gene expression that is important for cell homeostasis. The clock mechanism is present in all cells, including the myocites, and disruption of the muscle clock is associated with changes in muscle phenotype and function.

On this regard, the purpose of this study is to evaluate whether the uremic milieu can negatively influence the clock mechanism in muscle cells, being another cause of reduced muscle quality in patients with ESKD. For that, an in vitro experiment will be performed by exposing muscular cells to serum from uremic patients. Sex and age matched controls will also be used. 

This study will be performed in collaboration to Prof Karyn Esser from the Department of Physiology & Aging, College of Medicine, University of Florida.

Researchers involved in this study

Peter Stenvinkel, Principal investigator
Alice Sabatino 
Carla Maria Avesani
Karolina Kublickiene

Protein energy wasting (PEW) refers to the multiple nutritional disorders often present in patients on hemodialysis (HD) with a prevalence among European countries varying from 28 to 54%. A variety of strategies are available to provide nutrition support to patients receiving HD at risk or diagnosed with PEW, they are: nutritional counseling, oral nutritional supplementation, enteral nutrition and intradialytic parenteral nutrition (IDPN). In particular, IDPN has the advantage of providing nutritional support using the HD access with no need for additional venous catheter placement. Clinical trials using IDPN to treat PEW showed improvement in anthropometric measurements when combined with nutritional counseling.

The aim of this project, that was developed in collaboration with the European Renal Nutrition (ERN) working group of the European Renal Association (ERA), is to collect anonymous information on patterns of IDPN access and use in Europe. The overall ambition is to identify potential knowledge gaps where we could counteract by generating education materials/courses to clinicians, and with the reported practice patterns potentially develop proposal protocols of how to use this therapy in practice.

Researchers involved in this study

Carla Maria Avesani. Principal investigator 
Juan Jesus Carrero
Alice Sabatino, and 
The ERN Working Group of the ERA Society.

Funding

Baxter Nutrition Europe

We, Peter Stenvinkel and Carla Avesani, also participate in these two Erasmus+ projects:

GoodREnal

GoodRENal is a European project aimed at promoting healthy lifestyle habits in people with chronic kidney disease. Researchers from Sweden, Greece, Belgium and Spain are working on this project, which is funded by the Erasmus+ European programme and the Spanish R+D+i Plan.

E-planet

The aim of the Erasmus+ funded ePlanet project is to provide educational resources on planetary health that can easily be integrated in several educational contexts or formats. 

The central element of the project is the ePlanet game, an introduction to planetary health topics. In this educational game, players are presented with a node network, depicting different planetary health challenges organized around the topics of food, air pollution and heat, infectious diseases, and cross-cutting planetary health issues.