title: Intradialytic creatine supplementation: A scientific rationale for improving the health and quality of life of dialysis patients.
abstract: The CK/PCr-system, with creatine (Cr) as an energy precursor, plays a crucial role in cellular physiology. In the kidney, as in other organs and cells with high and fluctuating energy requirements, energy-charged phospho-creatine (PCr) acts as an immediate high-energy source and energy buffer, and as an intracellular energy transport vehicle. A maximally filled total Cr (Cr plus PCr) pool is a prerequisite for optimal functioning of the body and its organs, and health. Skeletal- and cardiac muscles of dialysis patients with chronic kidney disease (CKD) are depleted of Cr in parallel with the duration of dialysis. The accompanying accumulation of cellular damage seen in CKD patients lead to a deterioration of musculo-skeletal and neurological functioning and poor quality of life (QOL). Therefore, to counteract Cr depletion, it is proposed to supplement CKD patients with Cr. The anticipated benefits include previously documented improvements in the musculo-skeletal system, brain and peripheral nervous system, as well as improvements in the common comorbidities of CKD patients (see below). Thus, with a relatively simple, safe and inexpensive Cr supplementation marked improvements in quality of life (QOL) and life span are likely reached. To avoid Cr and fluid overload by oral Cr administration, we propose intradialytic Cr supplementation, whereby a relatively small amount of Cr is added to the large volume of dialysis solution to a final concentration of 1-10mM. From there, Cr enters the patient's circulation by back diffusion during dialysis. Because of the high affinity of the Cr transporter (CRT) for Cr affinity for Cr (Vmax of CRT for Cr=20-40μM Cr), Cr is actively transported from the blood stream into the target cells and organs, including skeletal and cardiac muscle, brain, proximal tubules of kidney epithelial cells, neurons, and leukocytes and erythrocytes, which all express CRT and depend on the CK/PCr system. By this intradialytic strategy, only as much Cr is taken up by the body as is needed to fill the tissue Cr pools and no excess Cr has to be excreted, as is the case with oral Cr. Because aqueous solutions of Cr are not very stable, Cr must be added immediately before dialysis either as solid Cr powder or from a frozen Cr stock solution to the dialysate, or alternatively, Cr could become an additional component of a novel dry dialysate mixture in a cartridge device.
authors.affiliation: Formerly at Dept. of Biology ETH-Zurich, Zurich, Switzerland. Electronic address: theo.wallimann@cell.biol.ethz.ch.
authors.forename: Theo
authors.initials: T
authors.lastname: Wallimann
authors.affiliation: Formerly at Dept. of Biology ETH-Zurich, Zurich, Switzerland.
authors.forename: Uwe
authors.initials: U
authors.lastname: Riek
authors.affiliation: Nephrology Klinik Im Park, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Möddel
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D015519:Bone Density; D003401:Creatine; D003404:Creatinine / Q000008:administration & dosage* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007511:Ischemia; D007668:Kidney / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D011788:Quality of Life; D006435:Renal Dialysis / Q000379:methods*; D051437:Renal Insufficiency / Q000523:psychology / Q000628:therapy*
chemical_list: D026901:Membrane Transport Proteins; C080679:creatine transporter; D003404:Creatinine; D003401:Creatine
keywords: Atherosclerosis; CKD patients; Cardiovascular complications; Chronic dialysis treatment; Depressions; Diabetes mellitus type-2; Dialysis patients; Dyslipidemia; Fatty liver disease; Hemodialysis and peritoneal dialysis with creatine; Hyper-homo-cysteinemia; Inflammation; Insulin sensitivity; Intra-dialytic or oral creatine supplementation; Kidney failure; Kidney insufficiency; Kidney transplant; Mental fatigue; Metabolic syndrome; Muscle fatigue; Muscle loss; NAFL; NASH; Protection by creatine of erythrocytes and immune cells; Protection from oxidative damage and mechanical stress by creatine; Sarcopenia; Sparing of erythropoietin (EPO); X-ray contrast media induced kidney failure