Tubular secretion in CKD

Astrid M. Suchy-Dicey, Thomas Laha, Andrew Hoofnagle, Rick Newitt, Tammy L. Sirich, Timothy W. Meyer, Ken E. Thummel, Norbert Yanez, Jonathan Himmelfarb, Noel S. Weiss, Bryan R. Kestenbaum

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2148-2155
Number of pages8
JournalJournal of the American Society of Nephrology
Volume27
Issue number7
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

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Kidney
Kidney Diseases
Dialysis
Indican
Confidence Intervals
Mortality
Proportional Hazards Models
Liquid Chromatography
Electrolytes
Urea
Albumins
Creatinine
Cohort Studies
Urine
Prospective Studies
Serum
Pharmaceutical Preparations
4-cresol sulfate
cinnamoylglycine
hippuric acid

ASJC Scopus subject areas

  • Nephrology

Cite this

Suchy-Dicey, A. M., Laha, T., Hoofnagle, A., Newitt, R., Sirich, T. L., Meyer, T. W., ... Kestenbaum, B. R. (2016). Tubular secretion in CKD. Journal of the American Society of Nephrology, 27(7), 2148-2155. https://doi.org/10.1681/ASN.2014121193

Tubular secretion in CKD. / Suchy-Dicey, Astrid M.; Laha, Thomas; Hoofnagle, Andrew; Newitt, Rick; Sirich, Tammy L.; Meyer, Timothy W.; Thummel, Ken E.; Yanez, Norbert; Himmelfarb, Jonathan; Weiss, Noel S.; Kestenbaum, Bryan R.

In: Journal of the American Society of Nephrology, Vol. 27, No. 7, 01.01.2016, p. 2148-2155.

Research output: Contribution to journalArticle

Suchy-Dicey, AM, Laha, T, Hoofnagle, A, Newitt, R, Sirich, TL, Meyer, TW, Thummel, KE, Yanez, N, Himmelfarb, J, Weiss, NS & Kestenbaum, BR 2016, 'Tubular secretion in CKD', Journal of the American Society of Nephrology, vol. 27, no. 7, pp. 2148-2155. https://doi.org/10.1681/ASN.2014121193
Suchy-Dicey AM, Laha T, Hoofnagle A, Newitt R, Sirich TL, Meyer TW et al. Tubular secretion in CKD. Journal of the American Society of Nephrology. 2016 Jan 1;27(7):2148-2155. https://doi.org/10.1681/ASN.2014121193
Suchy-Dicey, Astrid M. ; Laha, Thomas ; Hoofnagle, Andrew ; Newitt, Rick ; Sirich, Tammy L. ; Meyer, Timothy W. ; Thummel, Ken E. ; Yanez, Norbert ; Himmelfarb, Jonathan ; Weiss, Noel S. ; Kestenbaum, Bryan R. / Tubular secretion in CKD. In: Journal of the American Society of Nephrology. 2016 ; Vol. 27, No. 7. pp. 2148-2155.
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