title: Uremic toxin development in living kidney donors: a longitudinal study.
abstract: BACKGROUND
  Emerging evidence suggests that uremic toxins, in particular indoxyl sulfate (IS) and p-cresyl sulfate (PCS), may be involved in the pathogenesis of cardiovascular disease. Despite a significant increase in IS and PCS in patients with established kidney damage, the effect of a nephrectomy in non-chronic kidney disease patients is not yet known.
  
  
  METHODS
  Forty-two living kidney donors (Caucasian; 76% female [n=32]; 53 ± 10 years) were enrolled in an observational cohort study and followed up annually for 2 years (before nephrectomy, 1 and 2 years after nephrectomy). At each time point, patients underwent measurements of serum total and free IS and PCS (using ultrahigh-performance liquid chromatography), carotid intima-media thickness (a measure of arterial stiffness), brachial artery reactivity (both flow-mediated dilatation and sublingual glycerol trinitrate, markers of endothelial dysfunction), kidney function by Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C, and urate and high-sensitivity C-reactive protein using standard laboratory techniques.
  
  
  RESULTS
  Kidney function decreased by 30% after nephrectomy (absolute change estimated glomerular filtration rate 28 ± 6.9 and 27 ± 7.6 mL/min/1.73 m at 1 and 2 years, respectively), and the concentration of toxin levels increased by 44% to 100%, which remained elevated at 2 years after nephrectomy (all P<0.001). Both toxins were associated with carotid intima-media thickness, brachial artery reactivity-glycerol trinitrate, serum urate, and C-reactive protein levels (all P<0.03). Further, IS and urate were found to be independent predictors of change in kidney function, from baseline at 2 years after nephrectomy (both P<0.03).
  
  
  CONCLUSIONS
  This study demonstrated significant and sustained increases in nephrovascular toxins, IS and PCS, after nephrectomy. Levels of both toxins were associated with clinically relevant markers of cardiovascular and renal risk, warranting further research in this area.
authors.affiliation: 1 Princess Alexandra Hospital, Brisbane, Queensland, Australia. 2 University of Queensland School of Medicine, Brisbane, Queensland, Australia. 3 Translational Research Institute, Brisbane, Queensland, Australia. 4 Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. 5 Address correspondence to: Nicole Isbel, Department of Nephrology, Princess Alexandra Hospital, Level 2, ARTS Building, Ipswich Road, Woolloongabba, Brisbane, Queensland 4102, Australia.
authors.forename: Megan
authors.initials: M
authors.lastname: Rossi
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Campbell
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.forename: Tony
authors.initials: T
authors.lastname: Stanton
authors.forename: Brian A
authors.initials: BA
authors.lastname: Haluska
authors.forename: Carmel M
authors.initials: CM
authors.lastname: Hawley
authors.forename: Goce
authors.initials: G
authors.lastname: Dimeski
authors.forename: Brett C
authors.initials: BC
authors.lastname: McWhinney
authors.forename: Jacobus P J
authors.initials: JP
authors.lastname: Ungerer
authors.forename: Omar M
authors.initials: OM
authors.lastname: Kaisar
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Isbel
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003408:Cresols / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D015994:Incidence; D007200:Indican / Q000097:blood*; D007668:Kidney / Q000503:physiopathology / Q000601:surgery; D016030:Kidney Transplantation; D019520:Living Donors; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy / Q000009:adverse effects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013463:Sulfuric Acid Esters / Q000097:blood*; D014511:Uremia / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; D007200:Indican