Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD.
BACKGROUND
Unlike the case with creatinine, conditions affecting the non-glomerular filtration rate (GFR) determinants of low-molecular-weight serum proteins, β-trace protein (BTP), β2-microglobulin (B2M), and cystatin C, are not well characterized.


METHODS
Pooled cross-sectional analysis of 3 studies.


METHODS
3,156 persons with chronic kidney disease from the MDRD (Modification of Diet in Renal Disease) Study, AASK (African American Study of Kidney Disease and Hypertension), and CRIC (Chronic Renal Insufficiency Cohort) Study.


METHODS
Demographic and clinical factors hypothesized to be associated with non-GFR determinants of the filtration markers, selected from literature review and physiologic and clinical considerations.


RESULTS
Serum creatinine, BTP, B2M, and cystatin C levels.


RESULTS
In multivariable-adjusted errors-in-variables regression models that included adjustment for measured GFR (mGFR) and mGFR measurement error, creatinine level had stronger associations with male sex, black race, and higher urine creatinine excretion than the other filtration markers. BTP was associated less strongly with age, similar in direction with sex, and opposite in direction with race than creatinine level. Like cystatin C, B2M level was associated less strongly with age, sex, and race than creatinine level. BTP, B2M, and cystatin C levels were associated more strongly than creatinine level with other factors, including urine protein excretion and weight for BTP, smoking and urine protein excretion for B2M, and smoking for cystatin C.


CONCLUSIONS
Findings may not be generalizable to populations without chronic kidney disease, and residual confounding with GFR due to incomplete adjustment for GFR measurement error.


CONCLUSIONS
Like creatinine, serum levels of low-molecular-weight proteins are affected by conditions other than GFR. Knowledge of these conditions can aid the interpretation of GFR estimates and risk using these markers and guide the use of these filtration markers in developing GFR estimating equations.
Division of Nephrology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guanghzou, China.
Xun
X
Liu
Tufts Medical Center, Boston, MA.
Meredith C
MC
Foster
Tufts Medical Center, Boston, MA.
Hocine
H
Tighiouart
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Amanda H
AH
Anderson
Cleveland Clinic, Cleveland, OH.
Gerald J
GJ
Beck
University of Miami Miller School of Medicine, Miami, FL.
Gabriel
G
Contreras
Johns Hopkins University School of Medicine, Baltimore, MD.
Josef
J
Coresh
University of Minnesota, Minneapolis, MN.
John H
JH
Eckfeldt
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Harold I
HI
Feldman
University of Utah, Salt Lake City, UT.
Tom
T
Greene
Department of Medicine, Tulane University School of Medicine, New Orleans, LA.
L Lee
LL
Hamm
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
Jiang
J
He
Department of Medicine, Metrohealth, Cleveland, OH.
Edward
E
Horwitz
Vanderbilt Medical Center, Nashville, TN.
Julia
J
Lewis
Division of Nephrology, Department of Medicine, University of Illinois at Chicago, Chicago, IL.
Ana C
AC
Ricardo
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Haochang
H
Shou
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
Raymond R
RR
Townsend
Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD.
Matthew R
MR
Weir
Tufts Medical Center, Boston, MA.
Lesley A
LA
Inker
Tufts Medical Center, Boston, MA. Electronic address: alevey@tuftsmedicalcenter.org.
Andrew S
AS
Levey
D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D055316:Cystatin C / Q000097:blood; D005919:Glomerular Filtration Rate; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood; D007677:Kidney Function Tests; D054834:Lipocalins / Q000097:blood; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000097:blood
D015415:Biomarkers; D001798:Blood Proteins; D055316:Cystatin C; D054834:Lipocalins; D001613:beta 2-Microglobulin; D003404:Creatinine; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase
Glomerular filtration rate (GFR); beta trace protein (BTP); beta-2 microglobulin (B2M); biomarker; creatinine; cystatin C; determinants of kidney function; estimation of kidney function; filtration marker; kidney disease
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