Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD

Xun Liu, Meredith C. Foster, Hocine Tighiouart, Amanda H. Anderson, Gerald J. Beck, Gabriel Contreras, Josef Coresh, John H. Eckfeldt, Harold I. Feldman, Tom Greene, L. Lee Hamm, Jiang He, Edward Horwitz, Julia Lewis, Ana C. Ricardo, Haochang Shou, Raymond R. Townsend, Matthew R. Weir, Lesley A. Inker, Andrew S. Levey & 7 others Lawrence J. Appel, Alan S. Go, Jiang He, John W. Kusek, James P. Lash, Akinlolu Ojo, Mahboob Rahman

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)892-900
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume68
Issue number6
DOIs
StatePublished - Dec 1 2016

Fingerprint

Creatinine
Cystatin C
Biomarkers
Molecular Weight
Chronic Renal Insufficiency
Urine
Proteins
Smoking
Diet Therapy
Kidney Diseases
Serum
African Americans
Renal Insufficiency
Blood Proteins
Cohort Studies
Cross-Sectional Studies
Demography
Hypertension
Kidney
Weights and Measures

Keywords

  • beta trace protein (BTP)
  • beta-2 microglobulin (B2M)
  • biomarker
  • creatinine
  • cystatin C
  • determinants of kidney function
  • estimation of kidney function
  • filtration marker
  • Glomerular filtration rate (GFR)
  • kidney disease

ASJC Scopus subject areas

  • Nephrology

Cite this

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD. / Liu, Xun; Foster, Meredith C.; Tighiouart, Hocine; Anderson, Amanda H.; Beck, Gerald J.; Contreras, Gabriel; Coresh, Josef; Eckfeldt, John H.; Feldman, Harold I.; Greene, Tom; Hamm, L. Lee; He, Jiang; Horwitz, Edward; Lewis, Julia; Ricardo, Ana C.; Shou, Haochang; Townsend, Raymond R.; Weir, Matthew R.; Inker, Lesley A.; Levey, Andrew S.; Appel, Lawrence J.; Go, Alan S.; He, Jiang; Kusek, John W.; Lash, James P.; Ojo, Akinlolu; Rahman, Mahboob.

In: American Journal of Kidney Diseases, Vol. 68, No. 6, 01.12.2016, p. 892-900.

Research output: Contribution to journalArticle

Liu, X, Foster, MC, Tighiouart, H, Anderson, AH, Beck, GJ, Contreras, G, Coresh, J, Eckfeldt, JH, Feldman, HI, Greene, T, Hamm, LL, He, J, Horwitz, E, Lewis, J, Ricardo, AC, Shou, H, Townsend, RR, Weir, MR, Inker, LA, Levey, AS, Appel, LJ, Go, AS, He, J, Kusek, JW, Lash, JP, Ojo, A & Rahman, M 2016, 'Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD', American Journal of Kidney Diseases, vol. 68, no. 6, pp. 892-900. https://doi.org/10.1053/j.ajkd.2016.07.021
Liu, Xun ; Foster, Meredith C. ; Tighiouart, Hocine ; Anderson, Amanda H. ; Beck, Gerald J. ; Contreras, Gabriel ; Coresh, Josef ; Eckfeldt, John H. ; Feldman, Harold I. ; Greene, Tom ; Hamm, L. Lee ; He, Jiang ; Horwitz, Edward ; Lewis, Julia ; Ricardo, Ana C. ; Shou, Haochang ; Townsend, Raymond R. ; Weir, Matthew R. ; Inker, Lesley A. ; Levey, Andrew S. ; Appel, Lawrence J. ; Go, Alan S. ; He, Jiang ; Kusek, John W. ; Lash, James P. ; Ojo, Akinlolu ; Rahman, Mahboob. / Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD. In: American Journal of Kidney Diseases. 2016 ; Vol. 68, No. 6. pp. 892-900.
@article{f54e9398f33f427fa8c66e4e71fe6418,
title = "Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD",
abstract = "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.",
keywords = "beta trace protein (BTP), beta-2 microglobulin (B2M), biomarker, creatinine, cystatin C, determinants of kidney function, estimation of kidney function, filtration marker, Glomerular filtration rate (GFR), kidney disease",
author = "Xun Liu and Foster, {Meredith C.} and Hocine Tighiouart and Anderson, {Amanda H.} and Beck, {Gerald J.} and Gabriel Contreras and Josef Coresh and Eckfeldt, {John H.} and Feldman, {Harold I.} and Tom Greene and Hamm, {L. Lee} and Jiang He and Edward Horwitz and Julia Lewis and Ricardo, {Ana C.} and Haochang Shou and Townsend, {Raymond R.} and Weir, {Matthew R.} and Inker, {Lesley A.} and Levey, {Andrew S.} and Appel, {Lawrence J.} and Go, {Alan S.} and Jiang He and Kusek, {John W.} and Lash, {James P.} and Akinlolu Ojo and Mahboob Rahman",
year = "2016",
month = "12",
day = "1",
doi = "10.1053/j.ajkd.2016.07.021",
language = "English (US)",
volume = "68",
pages = "892--900",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "6",

}

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, Josef

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 - He, Jiang

AU - Kusek, John W.

AU - Lash, James P.

AU - Ojo, Akinlolu

AU - Rahman, Mahboob

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 - 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 - Glomerular filtration rate (GFR)

KW - kidney disease

UR - http://www.scopus.com/inward/record.url?scp=84994765277&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994765277&partnerID=8YFLogxK

U2 - 10.1053/j.ajkd.2016.07.021

DO - 10.1053/j.ajkd.2016.07.021

M3 - Article

VL - 68

SP - 892

EP - 900

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

IS - 6

ER -