Comparative CKD risk prediction using homocitrulline and carbamylated albumin: two circulating markers of protein carbamylation Article Swipe
Aya Awwad
,
Eugene P. Rhee
,
Morgan E. Grams
,
Hernan Rincon Choles
,
James Sondheimer
,
Jiang He
,
Jing Chen
,
Chi‐yuan Hsu
,
Ramachandran S. Vasan
,
Paul L. Kimmel
,
Kendra E. Wulczyn
,
Anders H. Berg
,
Jim Lash
,
Mengyao Tang
,
Sahir Kalim
,
Amanda H. Anderson
,
Lawrence J. Appel
,
Debbie L. Cohen
,
Laura M. Dember
,
Alan S. Go
,
Robert G. Nelson
,
Mahboob Rahman
,
Panduranga S. Rao
,
Vallabh O. Shah
,
Mark L. Unruh
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1186/s12882-024-03619-6
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1186/s12882-024-03619-6
Background Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies. Methods Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2–4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker. Results Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35–2.66) for C-Alb, and 1.89 [1.27–2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10–1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707–0.743] with C-Alb and 0.725 [0.707–0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics. Conclusions C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1186/s12882-024-03619-6
- https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-024-03619-6
- OA Status
- gold
- Cited By
- 4
- References
- 41
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4399157020
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4399157020Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1186/s12882-024-03619-6Digital Object Identifier
- Title
-
Comparative CKD risk prediction using homocitrulline and carbamylated albumin: two circulating markers of protein carbamylationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-05-30Full publication date if available
- Authors
-
Aya Awwad, Eugene P. Rhee, Morgan E. Grams, Hernan Rincon Choles, James Sondheimer, Jiang He, Jing Chen, Chi‐yuan Hsu, Ramachandran S. Vasan, Paul L. Kimmel, Kendra E. Wulczyn, Anders H. Berg, Jim Lash, Mengyao Tang, Sahir Kalim, Amanda H. Anderson, Lawrence J. Appel, Debbie L. Cohen, Laura M. Dember, Alan S. Go, Robert G. Nelson, Mahboob Rahman, Panduranga S. Rao, Vallabh O. Shah, Mark L. UnruhList of authors in order
- Landing page
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https://doi.org/10.1186/s12882-024-03619-6Publisher landing page
- PDF URL
-
https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-024-03619-6Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
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-
goldOpen access status per OpenAlex
- OA URL
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https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-024-03619-6Direct OA link when available
- Concepts
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Medicine, Hazard ratio, Internal medicine, Confidence interval, Kidney disease, Nephrology, Proportional hazards model, Quartile, Prospective cohort study, EndocrinologyTop concepts (fields/topics) attached by OpenAlex
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4Total citation count in OpenAlex
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2025: 3, 2024: 1Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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