Plasma Levels of Biotin Metabolites Are Elevated in Hemodialysis Patients with Cramps

Abstract

Patients with renal failure undergoing hemodialysis (HD) are susceptible to muscle cramps during and after HD. Muscle cramps are defined as the sudden onset of a prolonged involuntary muscle contraction accompanied by severe pain. Through HD, water-soluble vitamins are drawn out with water. Since biotin, a water-soluble vitamin, plays an essential role as one of the coenzymes in producing energy, we have hypothesized that deficiency of biotin may be responsible for HD-associated cramps. We previously reported that biotin administration ameliorated the muscle cramps, despite the elevated plasma biotin levels before HD and biotin administration, as judged by an enzyme-linked immunosorbent assay (ELISA). However, the ELISA measures not only biotin but also total avidin-binding substances (TABS) including biotin metabolites. In the present study, we determined biotin in HD patients as well as healthy controls, using a newly developed method with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The plasma samples were collected from 28 HD patients (16 patients with cramps and 12 patients without cramps) before HD and biotin administration and from 11 controls. The results showed that the accumulation of biotin and TABS in plasma of HD patients compared to controls. Importantly, the levels of biotin metabolites, i.e. TABS subtracted by biotin, increased significantly in patients with cramps over those without cramps. Moreover, the levels of biotin metabolites were significantly higher in patients with a poor response to administered biotin, compared to those with a good response. We propose that accumulated biotin metabolites impair biotin's functions as a coenzyme.

Electrochemical Sensing of Biotin Using Nafion-Modified Boron-Doped Diamond Electrode

“…46 This critical issue has pointed out who require hemodialysis from the analysis of patients’ blood for biotins. 47 Of notice is the specific detection of biotin by the Nafion-modified BDD electrode because the above biotin analogs are not oxidized at this applied potential for the oxidation of biotin. Apparently, the difference between the results obtained by the electrode and the immunoassay reflects the level of the biotin analogs.…”

Microbiota Quality and Mitochondrial Activity Link with Occurrence of Muscle Cramps in Hemodialysis Patients using Citrate Dialysate: A Pilot Study

“…Thirty percent of HD patients under citrate dialysate (CD) would present HAMCs [5]. Despite palliative measures, no consistent effects have been obtained [6]. One of possible mechanisms of muscle cramps could be a disorder of muscle energy metabolism [4].…”

Impact of a designed isotonic exercise program on pain intensity of muscle cramps in legs of patients undergoing hemodialysis; a randomized clinical trial

“…Studies have shown that limb ischemia during filtration is one of the causes of cramps. Hyponatremia causes vasoconstriction and decreased blood supply to the muscles and, in response to ischemia, it causes cramps and pain through pain stimulus factors such as histamine and bradykinin secretion (9). These painful muscle cramps often complicate hemodialysis, but their exact mechanism is unclear (8)(9)(10)(11).…”

“…Hyponatremia causes vasoconstriction and decreased blood supply to the muscles and, in response to ischemia, it causes cramps and pain through pain stimulus factors such as histamine and bradykinin secretion (9). These painful muscle cramps often complicate hemodialysis, but their exact mechanism is unclear (8)(9)(10)(11). The results of a previous study showed that variables related to the hemodialysis process such as the round per minute (rpm) of pump, and the patient›s blood pressure and weight also affect the incidence of muscle cramps (12).…”