title: A linear relationship between the ex-vivo sodium mediated expression of two sodium regulatory pathways as a surrogate marker of salt sensitivity of blood pressure in exfoliated human renal proximal tubule cells: the virtual renal biopsy.
abstract: BACKGROUND
  Salt sensitivity (SS) of blood pressure (BP) affects 25% of adults, shares comorbidity with hypertension, and has no convenient diagnostic test. We tested the hypothesis that urine-derived exfoliated renal proximal tubule cells (RPTCs) could diagnose the degree of an individual's SS of BP.
  
  
  METHODS
  Subjects were selected who had their SS of BP determined 5 y prior to this study (salt-sensitive: ≥7 mm Hg increase in mean arterial pressure (MAP) following transition from a random weekly diet of low (10 mmol/day) to high (300 mmol/day) sodium (Na(+)) intake, N=4; inverse salt-sensitive (ISS): ≥7 mm Hg increase in MAP transitioning from a high to low Na(+) diet, N=3, and salt-resistant (SR): <7 mm Hg change in MAP transitioned on either diet, N=5). RPTC responses to 2 independent Na(+) transport pathways were measured.
  
  
  RESULTS
  There was a negative correlation between the degree of SS and dopamine-1 receptor (D1R) plasma membrane recruitment (y=-0.0107x+0.68 relative fluorescent units (RFU), R(2)=0.88, N=12, P<0.0001) and angiotensin II-stimulated intracellular Ca(++) (y=-0.0016x+0.0336, R(2)=0.7112, P<0.001, N=10) concentration over baseline.
  
  
  CONCLUSIONS
  Isolating RPTCs from urine provides a personalized cell-based diagnostic test of SS index that offers advantages over a 2-week controlled diet with respect to cost and patient compliance. Furthermore, the linear relationship between the change in MAP and response to 2 Na(+) regulatory pathways suggests that an individual's RPTC response to intracellular Na(+) is personalized and predictive.
authors: University of Virginia, Charlottesville, VA 22903, United States.
authors: John J
authors: JJ
authors: Gildea
authors: Dylan T
authors: DT
authors: Lahiff
authors: Robert E
authors: RE
authors: Van Sciver
authors: Ryan S
authors: RS
authors: Weiss
authors: Neema
authors: N
authors: Shah
authors: Helen E
authors: HE
authors: McGrath
authors: Cynthia D
authors: CD
authors: Schoeffel
authors: Pedro A
authors: PA
authors: Jose
authors: Robert M
authors: RM
authors: Carey
authors: Robin A
authors: RA
authors: Felder
mesh_terms: D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism; D062186:Arterial Pressure / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D012982:Sodium, Dietary / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D017447:Receptors, Dopamine D1; D012982:Sodium, Dietary; D000804:Angiotensin II; D002118:Calcium