Rat study suggests hemodialysis plus ketogenic diet could enhance cancer treatment

In a recent study published in the journal Scientific Reports, researchers investigated whether hemodialysis (HD) can maintain elevated blood ketone levels in rats on a ketogenic diet in an effort to enhance cancer treatment efficacy potentially.

Study: Experimental hemodialysis in diet-induced ketosis and the potential use of dialysis as an adjuvant cancer treatment. Image Credit: Inside Creative House / Shutterstock.com

Background 

Cancer, a significant global health challenge characterized by limited therapy options and frequent treatment resistance, may benefit from HD as a supplementary treatment to enhance survival rates in aggressive cancers. Standard treatments for cancer, such as surgery, radiation, and chemotherapy, may be enhanced by a ketogenic diet, which induces a metabolic state similar to prolonged fasting and could potentially overcome dietary challenges faced by cancer patients.

Glucose-free dialysis can replicate fasting effects by reducing insulin and glucose levels. Likewise, high-flux hemodialyzers may amplify ketosis when used with a ketogenic diet; however, this treatment may also reduce ketosis by removing ketone bodies.

Further research is needed to understand how hemodialysis can enhance ketosis and potentially improve cancer treatments, considering its metabolic effects and the need to balance ketone body removal.

About the study 

In the present study, six male Sprague-Dawley rats, each weighing approximately 316 grams, were used to assess the impact of HD following a five-day ketogenic diet. Initially fed a standard diet, rats were then transitioned to the ketogenic diet, with their care and experimental procedures strictly adhering to ethical standards and receiving approval from the relevant ethical committee.

Critical medical procedures included cannulation of veins and arteries for blood sampling, continuous monitoring, and facilitating connection to the HD apparatus. The dialysis process involved a specially prepared blood circuit, which was primed with albumin and heparin.

An advanced HD system equipped with a high-flux membrane dialyzer was utilized for the experiments. During the three-hour dialysis session, blood samples were periodically collected to monitor any physiological changes. Care was taken to manage the dialysis fluid and ensure no fluid loss from the animals.

The researchers also performed simulations to gain a deeper understanding of the impact of dialysis on blood composition. These simulations adapted a model suitable for human conditions and incorporated necessary adjustments to account for the dialysis-clearing effect and assumption of no nutrient intake during the process. This approach allowed for an in-depth evaluation of the effects of HD in a controlled experimental setting.

Study findings 

A five-day ketogenic diet in rats resulted in a weight gain ranging from 10-37 grams. Prior to dialysis, various baseline parameters such as arterial pH, actual bicarbonate, base excess, oxygen pressure (pO₂), and carbon dioxide pressure (pCO₂) were recorded. The three-hour HD procedure was followed by a 30-minute period of rest before concluding the experiment. 

HD did not significantly reduce blood ketone levels, as blood ketone levels before and after dialysis were similar. No notable changes in ketone concentrations were observed during the dialysis process.

The urea reduction ratio (URR) and glucose reduction ratio indicated a 38% and 36% decrease, respectively. The blood-to-dialysate clearance of 51Cr-Ethylenediaminetetraacetic acid (EDTA) remained stable throughout the session.

Regarding acid-base balance and blood chemistry, plasma base excess increased during dialysis, which led to increased arterial pH. However, arterial pCO₂ levels remained unchanged post-dialysis. Blood hemoglobin levels did not significantly change, whereas plasma potassium levels increased, and there was no significant difference in plasma sodium levels.

In-silico modeling was used to simulate the effects of dialysis on systemic blood composition. This modeling showed that significant lowering of blood glucose levels through dialysis can only be achieved after liver glycogen stores are depleted, which typically takes about three hours from the start of dialysis.

The simulation suggested delaying dialysis until this depletion occurs. Moreover, it was observed that dialysis reduced blood glucose and insulin levels while slightly increasing ketone levels. A second simulation, which assumed zero insulin clearance during dialysis, showed a significant reduction in glucose levels and a slight decrease in ketone levels; however, these levels were higher than without dialysis.

The transport patterns of key substances involved in the process were thoroughly analyzed. The delivery and removal of ketones to and from the blood were largely balanced, with dialysis constituting only a small fraction of these processes.

Dialysis had a more pronounced effect on glucose and insulin, as it significantly reduced consumption rates. When insulin clearance was set to zero, a slight reduction in the delivery and consumption of ketone and a very low turnover of glucose was observed.