Summary
Haemodialysis is a blood filtering treatment given to individuals whose kidneys are not functioning well. This can occur in conditions such as chronic kidney disease and end-stage renal disease. Haemodialysis patients are at severe elevated risk of (fatal) cardiovascular health events, such as heart attacks. Crucially, research findings points towards a positive role of DHA in cardiovascular health of patients undergoing haemodialysis.  
 
Introduction
Haemodialysis is a common (and often life-saving) treatment for individuals with severe functional impairment of their kidneys, such as in chronic kidney disease or end-stage renal disease. During haemodialysis treatment, patients are periodically coupled to a dialysis machine that filters their blood from waste products and fluid, taking over this function from the kidneys. One of the aims of this treatment is therefore supporting normal functioning of the cardiovascular system that supplies our tissues with oxygen, though haemodialysis cannot fully replace our kidneys’ function. Common conditions where haemodialysis is administered are chronic kidney disease and end-stage renal disease. In chronic kidney disease, a persisting functional impairment of the kidneys occurs, where they are not able to fully carry out their normal function. This can then transition into end-stage renal disease, where the kidneys begin to stop functioning completely.
 
As a crucial role of our kidneys is the filtration of blood, it follows that cardiovascular health is often poor in patients receiving haemodialysis, affecting up to two-thirds of patients. For example, around 50% of patients with end-stage renal disease die within 5 years, mostly due to cardiovascular diseases or health events such as arrythmias (irregular heartbeats) or cardiac arrests (heart attacks). Peripheral artery disease (narrowing of and reduced blood flow in arteries in the arms or legs) is commonly seen in haemodialysis patients, too. Markers for, amongst others, anaemia (low red blood cell or haemoglobin levels), oxidative stress and inflammation are often elevated in haemodialysis patients. An important function of the kidneys in health is production of EPO, a hormone that stimulates the synthesis of red blood cells, which in turn provide oxygen to our tissues using haemoglobin that they carry. In chronic kidney disease, the kidneys may fail to carry out this red blood cell producing function with EPO, leading to anaemia (as measured by low red blood cell or haemoglobin levels) and oxidative stress. Common treatment adjunctive to haemodialysis therefore includes administration of erythropoiesis (red blood cell production)-stimulating agents, though not all patients are equally responsive and some develop erythropoiesis resistance.
 
Finally, haemodialysis patients often suffer from dyslipidaemia (abnormal amounts of lipids or lipid-binding proteins in the blood). All the abovenamed factors are directly associated with an increased risk of cardiovascular disease risk and mortality in haemodialysis patients. Crucially, omega-3 fatty acids such as EPA and DHA have anti-inflammatory and antioxidant properties, and they are known for their beneficial effects towards cardiovascular health. Conversely, studies have shown that circulating DHA levels are inversely correlated with risk of mortality in haemodialysis patients. Correspondingly, supplementation with DHA (with or without EPA) has positive cardiovascular effects in haemodialysis patients, discussed below.
 
Research findings
Investigating the role of circulating DHA towards all-cause mortality in persons undergoing haemodialysis, Terashima and collaborators monitored a group of 176 haemodialysis patients for a period of 10 years (Terashima et al. 2014). The patient group had a mean age of 64 years and consisted of 96 men and 80 women, all receiving haemodialysis treatment. The authors monitored the concentration of DHA in red blood cells of haemodialysis patients, and divided this into tertiles: low, middle and high. This was then plotted against the number of deaths (97) that occurred in the 10 year period. As patients who died were amongst other factors more likely to be older and men, this analysis was then corrected for the potentially influencing factors. These were age, sex, smoking status, blood pressure, body mass index, haemodialysis treatment period, and certain cardiovascular health markers. After correction, the authors concluded that a high concentration of DHA in red blood cells was linked to a lower risk of all-cause mortality. This effect was especially pronounced in women.  
 
Kobayashi and colleagues set up a study to determine the effects of supplementation with EPA and DHA on markers of peripheral artery disease severity in haemodialysis patients with dyslipidaemia (Kobayashi et al. 2024). For a period of three months, 19 patients continued their normal treatment (control group) and 19 patients received high-dose supplementation of 1860mg EPA and 1500mg DHA per day (test group). All patients were allowed to follow their normal treatment regimen during the study. It should be noted that the authors did not correct for the placebo effect by opting not to give the control group a placebo. Rather, after the  3 month assessment point in the study, 16 of the 19 patients from the control group followed a low-dose DHA and EPA supplementation regime for three months. This data was then used to establish dose-dependent effects by comparing the low-dose supplementation with the high-dose supplementation data. The authors reported positive changes in markers of cardiovascular health in the high dose supplementation group, compared to the control group. Furthermore, they found that compared to the high dose group, the low dose supplementation resulted in a similar but less strong effect regarding markers of cardiovascular health. The authors concluded that supplementation with EPA and DHA has positive effects on cardiovascular health in haemodialysis patients, and that this effect is most pronounced with high doses.
 
Ruperto and colleagues set up a controlled clinical trial to determine the effects of DHA supplementation on cardiovascular health markers in haemodialysis patients (Ruperto et al. 2021). Forty-two adult patients (69% men, with a mean age of 66.7 years) receiving haemodialysis treatment for a minimum of 3 months were evenly divided into two groups. After each haemodialysis treatment (3 times per week), one group (21 individuals) received 645mg DHA; the other group (21 individuals) received no supplementation. During the entire study, patients continued to receive their standard treatment. At the beginning and end of this 8 week period, markers of EPO dose and resistance, and inflammation were analysed to investigate any effect of DHA supplementation. The authors found that supplementation with DHA caused a decrease in erythropoiesis resistance, the EPO dose required to obtain sufficient haemoglobin levels, and markers of inflammation. Thus, it was concluded that in this trial, supplementation with DHA for haemodialysis patients following their regular treatment had a positive effect on anaemia and inflammation.
 
Conclusion
Haemodialysis patients have poor kidney function and are at elevated risk of cardiovascular disease and mortality. Omega-3 fatty acids such as DHA are known for their positive cardiovascular health effects, which have been investigated in haemodialysis patients. The studies discussed above point towards a positive role of DHA in cardiovascular health and all-cause mortality in patients undergoing haemodialysis. Firstly, elevated levels of circulating DHA are associated with decreased mortality risk in haemodialysis patients. Moreover, supplementation trials with DHA or DHA and EPA in patients undergoing haemodialysis indicate that these omega-3 fatty acids have a positive effect towards markers of cardiovascular health, such as decreases in anaemia and inflammation. Moreover, the supplementation worked well together with the normal treatment haemodialysis patients received in these trials. Overall, DHA (either by itself or in combination with EPA) has positive effects on cardiovascular health in haemodialysis patients. 
 
References
Kobayashi, Yusuke, Tetsuya Fujikawa, Aiko Haruna, Rina Kawano, Moe Ozawa, Tatsuya Haze, Shiro Komiya, et al. 2024. ‘Omega-3 Fatty Acids Reduce Remnant-like Lipoprotein Cholesterol and Improve the Ankle–Brachial Index of Hemodialysis Patients with Dyslipidemia: A Pilot Study’. Medicina 60 (1): 75. https://doi.org/10.3390/medicina60010075.
 
Ruperto, Mar, Nuria Rodríguez-Mendiola, Martha Díaz-Domínguez, Sara Giménez-Moyano, M. Laura García-Bermejo, and Milagros Fernández-Lucas. 2021. ‘Effect of Oral Administration of Docohexanoic Acid on Anemia and Inflammation in Hemodialysis Patients: A Randomized Controlled Clinical Trial’. Clinical Nutrition ESPEN 41 (February): 129–35. https://doi.org/10.1016/j.clnesp.2020.12.004.
 
Terashima, Yoshihiro, Kei Hamazaki, Miho Itomura, Shin Tomita, Masahiro Kuroda, Hitoshi Hirata, Tomohito Hamazaki, and Hidekuni Inadera. 2014. ‘Inverse Association between Docosahexaenoic Acid and Mortality in Patients on Hemodialysis during over 10 Years’. Hemodialysis International 18 (3): 625–31. https://doi.org/10.1111/hdi.12128.