title: Unsupervised analysis of combined lipid and coagulation data reveals coagulopathy subtypes among dialysis patients.
abstract: Hemodialysis (HD) and peritoneal dialysis (PD) are the primary means of managing end stage renal disease (ESRD). However, these treatment modalities are associated with the onset of coagulation abnormalities. Effective management of coagulation risk among these patients requires the identification of surrogate markers that provide an early indication of the coagulation abnormalities. The role of sphingolipids in the manifestation and prediction of coagulation abnormalities among dialysis patients have never been investigated. Herein, we report the first instance of an in depth investigation into the sphingolipid changes among ESRD patients undergoing HD and PD. The results reveal distinct differences in terms of perturbations to specific sphingolipid biosynthetic pathways that are highly dependent on the treatment modality. Our studies also demonstrated strong correlation between specific sphingolipids and coagulation parameters, such as HexCer(d18:1/26:0) and maximal amplitude (MA), SM(d18:1/24:1) and tissue factor pathway inhibitor, and sphingosine 1-phosphate d18:1 and FX (Spearman ρ of 0.93, 0.89, and -0.89, respectively). Furthermore, our study revealed the potential for using HexCer(d18:1/22:0), HexCer(d18:1/24:0), and HexCer(d18:1/26:0) (r2= 0.71, 0.82, and 0.63, respectively) and coagulation parameter MA (r2= 0.7) for successful diagnosis of differential coagulopathies among ESRD patients undergoing HD, providing an opportunity toward personalized disease management.
authors.affiliation: Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University (VCU), Richmond, VA.
authors.forename: Daniel
authors.identifier: 0000-0002-3165-4192
authors.initials: D
authors.lastname: Contaifer
authors.affiliation: Departments of Internal Medicine, Virginia Commonwealth University (VCU), Richmond, VA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Carl
authors.affiliation: Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University (VCU), Richmond, VA.
authors.forename: Urszula Osinska
authors.initials: UO
authors.lastname: Warncke
authors.affiliation: Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University (VCU), Richmond, VA.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Martin
authors.affiliation: Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University (VCU), Richmond, VA.
authors.forename: Bassem M
authors.identifier: 0000-0001-7227-3663
authors.initials: BM
authors.lastname: Mohammed
authors.affiliation: Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University (VCU), Richmond, VA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Van Tassell
authors.affiliation: Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University (VCU), Richmond, VA wijesingheds@vcu.edu dbrophy@vcu.edu charles.chalfant@vcuhealth.org.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Brophy
authors.affiliation: Biochemistry and Molecular Biology, Virginia Commonwealth University (VCU), Richmond, VA wijesingheds@vcu.edu dbrophy@vcu.edu charles.chalfant@vcuhealth.org.|Hunter Holmes McGuire Veterans Administration Medical Center, VCU Johnson Center for Critical Care Research, VCU Massey Cancer Center, and VCU Institute of Molecular Medicine, Richmond, VA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Chalfant
authors.affiliation: Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University (VCU), Richmond, VA wijesingheds@vcu.edu dbrophy@vcu.edu charles.chalfant@vcuhealth.org.|Surgery, Virginia Commonwealth University (VCU), Richmond, VA.
authors.forename: Dayanjan S
authors.identifier: 0000-0002-2124-5109
authors.initials: DS
authors.lastname: Wijesinghe
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000473:pathology / Q000628:therapy; D050356:Lipid Metabolism; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D006435:Renal Dialysis / Q000009:adverse effects*; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000473:pathology / Q000628:therapy; D013107:Sphingolipids / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008246:Lysophospholipids; D013107:Sphingolipids; D013109:Sphingomyelins; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: coagulopathy; monohexosyl ceramide; renal disease; sphingolipids; sphingomyelin; sphingosine 1-phosphate