The Effect of Intradialytic Supplementation of Creatine in Chronic Hemodialysis Patients: a Pilot Study

Dialysis is a life-saving treatment, but unfortunately health-related quality of life (HRQoL) of dialysis patients is poor and mortality risks are high compared to the general population. Although several potentially modifiable (e.g. pre-dialysis care and nutritional status) and unmodifiable risk factors (e.g. age and genetics) for excess risk of mortality and poor HRQoL have been identified in dialysis-dependent patients with chronic kidney disease (CKD), there is great need for identification of new potentially modifiable risk factors. We hypothesize that creatine deficiency is such a modifiable risk factor, which underlies several important causes for impaired HRQoL hemodialysis patients, such as protein energy wasting (PEW), sarcopenia, fatigue, muscle weakness, depression, cognitive impairment, and increased susceptibility and a higher risk of an adverse course of infectious diseases. We propose that creatine supplementation is particularly important for patients with dialysis-dependent CKD because (1) endogenous synthesis of creatine in these patients is severely impaired due to the virtual absence of kidney function and, consequently, the virtual absence of the first enzymatic step required for endogenous absence of creatine from the amino acids arginine and glycine (2) unopposed losses of creatine to the dialysis fluid during dialysis sessions, and (3) inadequate intake of creatine due to advices towards a primary plant-based diet in these patients. All this comes on top of the normally existing continuous non-enzymatic conversion of approximately 1.6-1.7% of the endogenous creatine pool to creatinine, which necessitates continuous replenishment of creatine by the combination of endogenous synthesis and dietary intake to remain in steady-state. This is a novel understanding because until recently it was not recognized that kidney function is an important contributor to endogenous creatine synthesis, so that the capacity to of patients with dialysis-dependent CKD to maintain creatine homeostasis in the light of ongoing conversion of creatine into creatinine, additional unopposed losses of creatine to the dialysis fluid and an inadequate dietary intake is severely impaired. Patients with dialysis-dependent CKD could benefit from creatine supplementation by allowing for maintenance of their endogenous creatine pools, which would help them to sustain bodily functions which depend on creatine availability, including normal function of muscles, heart, the immune system and brain.

Based on these novel/ recent findings, we hypothesize that creatine, intradialytic creatine supplementation may help to maintain creatine homeostasis among dialysis-dependent chronic kidney disease patients, and consequently improve muscle status, nutritional status, neurocognitive status fatigue and HRQoL.

Objective: The primary objective of this pilot study is the feasibility of prolonged intra-dialytic creatine supplementation.

The secondary objectives of this pilot study are to study the safety of prolonged intra-dialytic creatine supplementation for dialysis patients and finding the optimal dosage to replenish the creatine pool, to this end we will step wisely increase creatine concentrations of the dialysis solution (in the range of 0.5 mM to a maximum of 2mM, with the latter reflecting the concentration that can be reached after an oral bolus of creatine).

The third objective is to obtain pilot data on the effect of intradialytic creatine supplementation on muscle status, nutritional status, neurocognitive status fatigue and HRQoL to allow for calculation of the power for a lager intervention study.