title: Tubular Secretion in CKD.
abstract: Renal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation.
authors.affiliation: Departments of Epidemiology and Kidney Research Institute, School of Medicine, astridsd@uw.edu.
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Suchy-Dicey
authors.affiliation: Department of Laboratory Medicine, and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Laha
authors.affiliation: Department of Laboratory Medicine, and.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hoofnagle
authors.affiliation: Kidney Research Institute, School of Medicine.
authors.forename: Rick
authors.initials: R
authors.lastname: Newitt
authors.affiliation: School of Medicine, Stanford University, Stanford, California.
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Sirich
authors.affiliation: School of Medicine, Stanford University, Stanford, California.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Meyer
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington; and.
authors.forename: Ken E
authors.initials: KE
authors.lastname: Thummel
authors.affiliation: Biostatistics, School of Public Health.
authors.forename: N David
authors.initials: ND
authors.lastname: Yanez
authors.affiliation: Kidney Research Institute, School of Medicine.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Himmelfarb
authors.affiliation: Departments of Epidemiology and.
authors.forename: Noel S
authors.initials: NS
authors.lastname: Weiss
authors.affiliation: Departments of Epidemiology and Kidney Research Institute, School of Medicine.
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Kestenbaum
mesh_terms: D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*
keywords: chronic kidney disease; epidemiology and outcomes; proximal tubule