#4580 ELEVATED LEVELS OF UREMIC SOLUTES IN THE CEREBROSPINAL FLUID OF HEMODIALYSIS PATIENTS

Abstract

Abstract Background and Aims Uremic solutes are considered as contributing factors to impaired cognitive function in end stage kidney disease (ESKD) [1]. However, the distribution and accumulation of uremic solutes in the central nervous system (CNS) of ESKD patients are not well understood. We measured four uremic solutes in the cerebrospinal fluid (CSF) and plasma of two ESKD patients and investigated the role of routine hemodialysis (HD) in clearing these solutes from their CNS. Method We accessed CSF in HD patients with a ventriculo-peritoneal shunt. A review of about 160,000 electronic health records revealed 30 eligible patients, two of whom consented to participate in this IRB-approved one-week study (Western IRB #20172182). On dialysis days, CSF and plasma were collected 2 hours pre- and 2 hours post-HD. Non-dialysis day samples were collected 20 hours post-HD. Samples from healthy subjects were purchased from BioIVT (Westbury, NY). Urea was measured using Horiba C400 Chemical Analyzer. Indoxyl sulfate (IS), p-cresol sulfate (pCS) and trimethylamine N-oxide (TMAO) were analyzed using Agilent Ultivo triple quadrupole mass spectrometer. The dialytic reduction ratio (RR; in %) was calculated as 100 × (pre-HD level – post-HD level) / pre-HD-level. Results In both CSF and plasma, levels of all four uremic solutes were elevated in HD patients compared to healthy subjects (Table 1). The ratio of CSF-to-plasma levels was <100% for all solutes. Ratios for HD patients are altered compared to those reported in healthy subjects (Table 1). Longitudinal plasma and CSF solute levels are shown in Figure 1. Plasma RRs for IS, pCS, TMAO and urea were 32%, 23%, 77%, and 67%, respectively. The respective CSF RRs were 29%, 20%, 3%, and 25%. Conclusion To the best of our knowledge, this is the first report on CSF levels of IS, pCS, and TMAO in HD patients. Our results indicate that uremic solute levels are elevated in the CSF from HD patients compared to healthy subjects. Moreover, HD only moderately reduces uremic solute levels in CSF. Whether increased CNS levels of uremic solutes are related to cognitive impairment warrants further investigation.