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

摘要

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 5y prior to this study (salt-sensitive: ≥7mm Hg increase in mean arterial pressure (MAP) following transition from a random weekly diet of low (10mmol/day) to high (300mmol/day) sodium (Na+) intake, N=4; inverse salt-sensitive (ISS): ≥7mm Hg increase in MAP transitioning from a high to low Na+ diet, N=3, and salt-resistant (SR): 7mm 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), R2=0.88, N=12, P0.0001) and angiotensin II-stimulated intracellular Ca++ (y=-0.0016x+0.0336, R2=0.7112, P0.001, 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.