Nocturnal hemodialysis and kidney transplantation: From vascular calcification to beyond

Abstract

Patients with end-stage kidney disease have a high risk of death, of which more than 50% of cases are caused by cardiovascular disease. An important role is played by their disturbed mineral metabolism. This includes high phosphate levels, which promote vascular calcification. Phosphate levels are significantly reduced by some renal replacement therapies, such as nocturnal hemodialysis (≥4x 8hrs per week) or kidney transplantation. However, it is unknown whether these therapies thus mitigate vascular calcification. Furthermore, the disturbed mineral metabolism affects the bone in end-stage kidney disease, resulting in an elevated fracture risk. Nevertheless, it is unclear whether patients with end-stage kidney disease also have an increased risk of vertebral fractures, which are often overlooked but are the most common type of fragility fracture. In this thesis, we therefore investigated the influence of renal replacement therapies on vascular calcification, and additionally investigated the risk of vertebral fractures and quality of life and mortality in end-stage kidney disease. We found that vascular calcification progresses in patients treated with conventional hemodialysis (3x 4hrs per week) and peritoneal dialysis, but that vascular calcification does not progress significantly less in nocturnal hemodialysis or kidney transplantation, despite substantial phosphate reductions and improvements in vitamin K status. This contrasts with the current paradigm that kidney transplant recipients have a lower cardiovascular disease risk compared to patients on dialysis due to reduced vascular calcification, raising the question whether vascular calcification is harmful in itself, or that it is merely an adaptive response to damage already done. On the other hand, we found a high prevalence (34%) of vertebral fractures in relatively young and healthy patients with end-stage kidney disease. With this substantially elevated risk, we believe patients with end-stage kidney disease may benefit from vertebral fracture screening. Finally, we also investigated quality of life and survival with nocturnal hemodialysis. We found that quality of life is superior after kidney transplantation compared to nocturnal hemodialysis. Furthermore, previous studies showed that survival is superior after kidney transplantation compared to nocturnal hemodialysis. Nevertheless, we also showed that patients treated with longer hemodialysis sessions (extended-hours hemodialysis) need far fewer pills, which may positively impact quality of life, that they have a lower mortality risk compared to patients treated with conventional hemodialysis. We therefore believe that nocturnal hemodialysis can provide an optimal dialysis therapy, and that we need to be able to identify patients that could benefit from nocturnal hemodialysis in clinical practice.