TY - JOUR
T1 - Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD
AU - Liu, Xun
AU - Foster, Meredith C.
AU - Tighiouart, Hocine
AU - Anderson, Amanda H.
AU - Beck, Gerald J.
AU - Contreras, Gabriel
AU - Coresh, Joe
AU - Eckfeldt, John H.
AU - Feldman, Harold I.
AU - Greene, Tom
AU - Hamm, L. Lee
AU - He, Jiang
AU - Horwitz, Edward
AU - Lewis, Julia
AU - Ricardo, Ana C.
AU - Shou, Haochang
AU - Townsend, Raymond R.
AU - Weir, Matthew R.
AU - Inker, Lesley A.
AU - Levey, Andrew S.
AU - Appel, Lawrence J.
AU - Go, Alan S.
AU - Kusek, John W.
AU - Lash, James P.
AU - Ojo, Akinlolu
AU - Rahman, Mahboob
N1 - Publisher Copyright:
© 2016 National Kidney Foundation, Inc.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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. Study Design Pooled cross-sectional analysis of 3 studies. Setting & Participants 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. Predictors 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. Outcomes 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. Limitations 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.
AB - 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. Study Design Pooled cross-sectional analysis of 3 studies. Setting & Participants 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. Predictors 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. Outcomes 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. Limitations 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.
KW - Glomerular filtration rate (GFR)
KW - beta trace protein (BTP)
KW - beta-2 microglobulin (B2M)
KW - biomarker
KW - creatinine
KW - cystatin C
KW - determinants of kidney function
KW - estimation of kidney function
KW - filtration marker
KW - kidney disease
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U2 - 10.1053/j.ajkd.2016.07.021
DO - 10.1053/j.ajkd.2016.07.021
M3 - Article
C2 - 27663042
AN - SCOPUS:84994765277
SN - 0272-6386
VL - 68
SP - 892
EP - 900
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -