TOWARD PERSONALIZED HAEMODIALYSIS BY LOW MOLECULAR WEIGHT AMINO-CONTAINING COMPOUNDS: FUTURE PERSPECTIVE OF PATIENT METABOLIC FINGERPRINT

Introduction and Aims: Patients on regular haemodialysis (HD) treatment generally tend to develop a state of carnitine deficiency due to reduced renal synthesis, poor dietary intake, and elevated intradialytic loss. This alteration may contribute to several abnormalities such as muscle pain, cardiomyopathy, cramps, and dyslipidemia. The aim of our study was to apply targeted metabolic fingerprint in order to evaluate the metabolic status of HD patients. Methods: Plasma levels of all carnitine esters (short – medium – and long chain) and of several aminoacids were quantified in a Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) multiplex experimental setup in 28 uraemic patients (13 non diabetics and 15 diabetics) and in 10 age-matched healthy controls. Samples were taken before and after the first HD treatment of the week. Multiplexed data were collected in LC-MRM (Multiple Reaction Monitoring) and analyzed by unsupervised multivariate analysis. Results:In diabetic uraemic patients, we observed lower values of propionylcarnitine than in other groups, while acylcarnitine concentration was higher in uraemics when compared to healthy controls. The HD session induced a decline in free, short-chain, medium-chain and dicarboxylic acylcarnitines, whereas the long chain acylcarnitines remained unaffected. Plasma levels of amino acid proline, ornithine, citrulline and serine were significantly elevated in uraemic patients before dialysis compared to controls. For most tested plasma amino acids, a significant reduction after haemodialysis session was found. Conclusions: Our study is the first that investigated on possible modifications of the system of carnitine in diabetic patients on haemodialysis not only in relation to the condition of deficiency but also compared to lipid and glucose homeostasis alterations typical of diabetes. Our results indicate that abnormalities in plasma carnitine profile are common in HD patients, regardless of the diabetic state. Patient metabolic fingerprint may be a convenient and useful tool to drive supplementation therapies targeted to normalize the altered plasma carnitine composition by a personalized approach, to the potential benefit of the patient.