Zhi-Hao Zhang1, Jia-Rong Mao2, Hua Chen3, Wei Su4, Yuan Zhang5, Li Zhang5, Dan-Qian Chen3, Ying-Yong Zhao6, Nosratola D Vaziri7. 1. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China; School of Traditional Chinese Pharmacy, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. 2. Department of Nephrology, Shaanxi Traditional Chinese Medicine Hospital, No. 2 Xihuamen, Xi'an, Shaanxi 710003, China. 3. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China. 4. Department of Nephrology, Baoji Central Hospital, No. 8 Jiangtan Road, Baoji, Shaanxi 721008, China. 5. Department of Nephrology, Xi'an No. 4 Hospital, No. 2 Jiefang Road, Xi'an, Shaanxi 710004, China. 6. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi 710069, China. Electronic address: zyy@nwu.edu.cn. 7. Division of Nephrology and Hypertension, School of Medicine, University of California Irvine, Irvine, CA 92897, USA. Electronic address: ndvaziri@uci.edu.
Abstract
BACKGROUND: Although dialysis ameliorates uremia and fluid and electrolytes disorders, annual mortality rate remains high in dialysis population reflecting its shortcoming in replacing renal function. Unlike the normal kidney, dialysis causes dramatic shifts in volume and composition of body fluids and indiscriminate removal of vital solutes. Present study was undertaken to determine the impact of hemodialysis on plasma metabolites in end-stage renal disease (ESRD) patients. METHODS: 80 hemodialysis patients and 80 age/gender-matched healthy controls were enrolled in the study. Using ultra performance liquid chromatography-high-definition mass spectrometry, we measured plasma metabolites before, during, and after hemodialysis procedure and in blood entering and leaving the dialysis filter. RESULTS: Principal component analysis revealed significant difference in concentration of 214 metabolites between healthy control and ESRD patients' pre-dialysis plasma (126 increased and 88 reduced in ESRD group). Comparison of post-dialysis with pre-dialysis data revealed significant changes in the 362 metabolites. Among ESI+ metabolites 195 decreased and 55 increased and among ESI- metabolites 82 decreased and 30 increased following hemodialysis. Single blood passage through the dialyzer caused significant changes in 323 metabolites. Comparison of ESRD patients' post-hemodialysis with healthy subjects' data revealed marked differences in metabolic profiles. We identified 55 of the 362 differential metabolites including well known uremic toxins, waste products and vital biological compounds. CONCLUSION: In addition to uremic toxins and waste products hemodialysis removes large number of identified and as-yet un-identified metabolites. Depletion of vital biological compounds by dialysis may contribute to the high morbidity and annual mortality rate in this population.
BACKGROUND: Although dialysis ameliorates uremia and fluid and electrolytes disorders, annual mortality rate remains high in dialysis population reflecting its shortcoming in replacing renal function. Unlike the normal kidney, dialysis causes dramatic shifts in volume and composition of body fluids and indiscriminate removal of vital solutes. Present study was undertaken to determine the impact of hemodialysis on plasma metabolites in end-stage renal disease (ESRD) patients. METHODS: 80 hemodialysis patients and 80 age/gender-matched healthy controls were enrolled in the study. Using ultra performance liquid chromatography-high-definition mass spectrometry, we measured plasma metabolites before, during, and after hemodialysis procedure and in blood entering and leaving the dialysis filter. RESULTS: Principal component analysis revealed significant difference in concentration of 214 metabolites between healthy control and ESRDpatients' pre-dialysis plasma (126 increased and 88 reduced in ESRD group). Comparison of post-dialysis with pre-dialysis data revealed significant changes in the 362 metabolites. Among ESI+ metabolites 195 decreased and 55 increased and among ESI- metabolites 82 decreased and 30 increased following hemodialysis. Single blood passage through the dialyzer caused significant changes in 323 metabolites. Comparison of ESRDpatients' post-hemodialysis with healthy subjects' data revealed marked differences in metabolic profiles. We identified 55 of the 362 differential metabolites including well known uremic toxins, waste products and vital biological compounds. CONCLUSION: In addition to uremic toxins and waste products hemodialysis removes large number of identified and as-yet un-identified metabolites. Depletion of vital biological compounds by dialysis may contribute to the high morbidity and annual mortality rate in this population.