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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Soc+Nephrol
2016 ; 27
(7
): 2148-55
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Tubular Secretion in CKD
#MMPMID26614381
Suchy-Dicey AM
; Laha T
; Hoofnagle A
; Newitt R
; Sirich TL
; Meyer TW
; Thummel KE
; Yanez ND
; Himmelfarb J
; Weiss NS
; Kestenbaum BR
J Am Soc Nephrol
2016[Jul]; 27
(7
): 2148-55
PMID26614381
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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.
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