Comparison of Serum Concentrations of β-Trace Protein, β2-Microglobulin, Cystatin C, and Creatinine in the US Population

Juraschek, Stephen P.; Coresh, Josef; Inker, Lesley A.; Levey, Andrew S.; Köttgen, Anna; Foster, Meredith C.; Astor, Brad C.; Eckfeldt, John H.; Selvin, Elizabeth

doi:10.2215/cjn.08700812

Cited by 59 publications

(54 citation statements)

References 36 publications

(44 reference statements)

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“…9,29,44 Similarly in NHANES III, several factors are associated with higher serum BTP and B2M, including older age, hypertension, higher CRP, and lower HDL-cholesterol, whereas female sex and non-Hispanic black and Hispanic race/ethnicity are associated with lower BTP and lower body mass index is associated with lower B2M. 45 Some have suggested that BTP may play a role in cardiovascular disease, potentially through atherosclerotic pathways. BTP expression has been observed in heart tissue and BTP accumulation has been observed in atherosclerotic plaques.…”

Section: Discussionmentioning

confidence: 98%

Novel Filtration Markers as Predictors of All-Cause and Cardiovascular Mortality in US Adults

Foster

Inker

Levey

et al. 2013

American Journal of Kidney Diseases

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Background New filtration markers, including β-trace protein (BTP) and β2-microglobulin (B2M), may, similar to cystatin C, enable a stronger prediction of mortality compared to serum creatinine-based estimated glomerular filtration rate (eGFRcr). We sought to evaluate these mortality associations in a representative sample of US adults. Study Design Prospective cohort study. Setting & Participants 6445 adults age ≥ 20 years from the Third National Health and Nutrition Examination Survey (1988–1994) with mortality linkage through December 31, 2006. Predictors Serum cystatin C, BTP, and B2M and eGFRcr categorized into quintiles, with the highest quintile (lowest for eGFRcr) split into tertiles (sub-quintile Q5a–Q5c). Outcomes All-cause, cardiovascular disease, and coronary heart disease mortality. Measurements Demographic and multivariable adjusted Cox proportional hazard models. Results During follow-up, 2392 deaths (cardiovascular, 1079; coronary heart disease, 605) occurred. All four filtration markers were associated with mortality risk after adjusting for demographics (p-trend<0.02). Adjusted for mortality risk factors, compared to the middle quintile, the highest sub-quintiles for cystatin C (Q5c: HR, 1.94; 95% CI, 1.43–2.62), BTP (Q5c: HR, 2.14; 95% CI, 1.56–2.94), and B2M (Q5c: HR, 2.58; 95% CI, 1.96–3.41) were associated with increased all-cause mortality risk while the association was weaker for eGFRcr (Q5c: HR, 1.31; 95% CI, 0.84–2.04). Associations persisted for the novel markers and not for eGFRcr at eGFRcr ≥60 mL/min/1.73 m2. Trends were similar for cardiovascular disease and coronary heart disease mortality. Limitations Single measurements of markers from long-term stored samples. Conclusions The strong association of cystatin C with mortality compared to serum creatinine estimates is shared by BTP and B2M. This supports the utility of alternative filtration markers beyond creatinine when improved risk prediction related to decreased GFR is needed.

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Section: Discussionmentioning

confidence: 98%

Novel Filtration Markers as Predictors of All-Cause and Cardiovascular Mortality in US Adults

Foster

Inker

Levey

et al. 2013

American Journal of Kidney Diseases

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“…In NHANES III, elevated BTP and B2M were associated with several factors that can also increase ESRD or mortality risk, including higher age, higher body mass index, hypertension, higher C-reactive protein, and lower HDL cholesterol for elevated B2M and higher age, male sex, race/ethnicity, hypertension, higher C-reactive protein, and lower HDL cholesterol for elevated BTP. 23 Serum B2M is also elevated in multiple myeloma and is part of risk stratification guidelines for this condition. 24 Additional potential non-GFR determinants for elevated BTP include genetic factors, cardiovascular disease, pregnancy, muscle mass, and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Filtration Markers as Predictors of ESRD and Mortality in Southwestern American Indians With Type 2 Diabetes

Foster

Inker

Hsu

et al. 2015

American Journal of Kidney Diseases

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Background A growing number of serum filtration markers are associated with mortality and end-stage renal disease (ESRD) in adults. Whether β-trace protein (BTP) and β2-microglobulin (B2M) are associated with these outcomes in adults with type 2 diabetes is not known. Study Design Longitudinal cohort study. Setting & Participants 250 Pima Indians with type 2 diabetes (69% women; mean age, 42 years; mean diabetes duration, 11 years). Predictors Serum BTP, B2M, and glomerular filtration rate measured by iothalamate clearance (mGFR) or estimated using creatinine (eGFRcr) or cystatin C (eGFRcys). Outcomes & Measurements Incident ESRD and all-cause mortality through December 2013. HRs were reported per interquartile range decrease of the inverse of BTP and B2M (1/BTP and 1/B2M) using Cox regression. Improvement in risk prediction with the addition of BTP or B2M to established markers (eGFRcys with mGFR or eGFRcr) was evaluated using C-statistics, continuous net reclassification improvement (NRI), and relative integrated discrimination improvement (rIDI). Results During median follow-up of 14 years, 69 participants developed ESRD and 95 died. Both novel markers were associated with ESRD in multivariable models. BTP remained statistically significant after further adjustment for mGFR (1/BTP, 1.53 [95% CI, 1.01-2.30]; 1/B2M, 1.54 [95% CI, 0.98-2.42]). B2M was associated with mortality in multivariable models and after further adjustment for mGFR (HR, 2.12; 95% CI, 1.38-3.26). The addition of B2M to established markers increased the C statistic for mortality but only weakly when assessed by either continuous NRI or rIDI; none were improved for ESRD by the addition of these markers. Limitations Small sample size, single measures of markers. Conclusions In Pima Indians with type 2 diabetes, BTP, and to a lesser extent B2M, was associated with ESRD. B2M was associated with mortality after adjustment for traditional risk factors and established filtration markers. Further studies are warranted to confirm whether inclusion of B2M in a multi-marker approach leads to improved risk prediction for mortality in this population..

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“…Elevated B2M in our large amputee group may be attributable to chronic inflammation. Modestly increased CRP is associated with elevated levels of B2M, but not BTP, SCr, or cystatin C [29]. Amputation is associated with increased pulse wave forms and increased pulse wave forms are associated with inflammation and elevated CRP [30,31,32].…”

Section: Discussionmentioning

confidence: 99%

Effects of Traumatic Amputation on β-Trace Protein and β2-Microglobulin Concentrations in Male Soldiers

Little

Yuan²,

Thurlow³

et al. 2015

Am J Nephrol

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Background: Serum creatinine (SCr) levels are decreased following traumatic amputation, leading to the overestimation of glomerular filtration rate (GFR). β-Trace protein (BTP) and β₂-microglobulin (B2M) strongly correlate with measured GFR and have not been studied following amputation. We hypothesized that BTP and B2M would be unaffected by traumatic amputation. Methods: We used the Department of Defense Serum Repository to compare pre- and post-traumatic amputation serum BTP and B2M levels in 33 male soldiers, via the N Latex BTP and B2M nephelometric assays (Siemens Diagnostics, Tarrytown, N.Y., USA). Osterkamp estimation using DEXA scan measurements was used to establish percent estimated body weight loss (%EBWL). Results were analyzed for small (3-5.9% EBWL), medium (6-13.5%), and large (>13.5%) amputation subgroups; and for a control group matched 1:1 to the 12 large amputation subjects. Paired Student's t test was used for comparisons. Results: Mean serum BTP levels were unchanged in controls, all amputees, and the small and medium amputation subgroups. BTP appeared to decrease following large %EBWL amputation (p = 0.05). Mean serum B2M levels were unchanged in controls, all amputees, and the small and medium amputation subgroups. B2M appeared to increase following large %EBWL amputation (p = 0.05). Conclusions: BTP and B2M levels are less affected than SCr by amputation, and should be considered for future study of GFR estimation. BTP and B2M changes following large %EBWL amputation require validation and may offer insight into non-GFR BTP and B2M determinants as well as increased cardiovascular disease and mortality following amputation. This is a work of the US Government and is not subject to copyright protection in the USA. Foreign copyrights may apply. Published by S. Karger AG, Basel

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Comparison of Serum Concentrations of β-Trace Protein, β2-Microglobulin, Cystatin C, and Creatinine in the US Population

Cited by 59 publications

References 36 publications

Novel Filtration Markers as Predictors of All-Cause and Cardiovascular Mortality in US Adults

Novel Filtration Markers as Predictors of All-Cause and Cardiovascular Mortality in US Adults

Filtration Markers as Predictors of ESRD and Mortality in Southwestern American Indians With Type 2 Diabetes

Effects of Traumatic Amputation on β-Trace Protein and β2-Microglobulin Concentrations in Male Soldiers

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