Evidence map›Paper›PMID 38816682›Full record

ArticleBMC nephrology2024

Comparative CKD risk prediction using homocitrulline and carbamylated albumin: two circulating markers of protein carbamylation.

Aya Awwad, Eugene P Rhee, Morgan Grams, Hernan Rincon Choles, James Sondheimer, Jiang He, Jing Chen, Chi-Yuan Hsu, Ramachandran S Vasan, Paul L Kimmel and 6 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC nephrology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Mechanisms of Homoarginine: Looking Beyond Clinical Outcomes.Acta physiologica (Oxford, England) · 2025
    Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Aya AwwadDepartment of Medicine, Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Eugene P RheeDepartment of Medicine, Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Morgan GramsDepartment of Medicine, New York University, New York, NY, USA.
Hernan Rincon CholesDepartment of Nephrology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
James SondheimerDepartment of Medicine, Wayne State University, Detroit, MI, USA.
Jiang HeDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Jing ChenDepartment of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Chi-Yuan HsuDivision of Nephrology, University of California San Francisco School of Medicine, San Francisco, CA, USA.
Ramachandran S VasanDepartment of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
Paul L KimmelDivision of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, USA.
Kendra WulczynDepartment of Medicine, Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Anders BergDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Jim LashDepartment of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Mengyao TangDepartment of Medicine, Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Sahir KalimDepartment of Medicine, Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. skalim@mgh.harvard.edu.
CRIC Study Investigators

Funding

Proposal for a Chicago-CRIC Clinical CenterU01DK060980 · UNIVERSITY OF ILLINOIS AT CHICAGO · 2001 to 2025
$3.2M
Continuation of the Chronic Renal Insufficiency Cohort (CRIC)U24DK060990 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$1.1M
NHLBI NIH HHS R01 HL133399NHLBI NIH HHS R01HL133399NIDDK NIH HHS K24 DK092290NIDDK NIH HHS R01 DK124453NIDDK NIH HHS R01DK124453NIDDK NIH HHS U01 DK060980NIDDK NIH HHS U24 DK060990
6 · The paper itself

Abstract

backgroundProtein 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.

methodsBoth 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.

resultsParticipant 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.

conclusionsC-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.

Indexed as

BiomarkersCitrullineProtein CarbamylationRenal Insufficiency, ChronicAgedFemaleHumansKidney Failure, ChronicMaleMiddle AgedPrognosisProportional Hazards ModelsProspective StudiesRisk AssessmentSerum AlbuminBiomarkersCitrullinehomocitrullineSerum AlbuminBiomarkerCarbamylated albuminCarbamylationChronic kidney diseaseHomocitrulline

Identifiers

PMID38816682
PMCPMC11140876

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.