Cardiovascular disease (CVD) is a highly common complication and the first cause of death in patients with end-stage renal disease (ESRD) on haemodialysis (HD). In this population, mortality due to CVD is 20 times higher than in the general population and the majority of maintenance HD patients have CVD. This is likely due to ventricular hypertrophy as well as non-traditional risk factors, such as chronic volume overload, anaemia, inflammation, oxidative stress, chronic kidney disease–mineral bone disorder and other aspects of the ‘uraemic milieu’. Better understanding the impact of these numerous factors on CVD would be an important step for prevention and treatment. In this review we focus non-traditional CVD risk factors in HD patients.

Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death [adjusted hazard ratio (aHR) 0.89], but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73 m²) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31–1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.

Advances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.