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Abstract: TH-PO240

Interaction of Glycation and Carbamylation in Diabetic CKD: Insights From the CRIC Study

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical


  • Tang, Mengyao, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Lash, James P., University of Illinois Chicago UI Health, Chicago, Illinois, United States
  • Kalim, Sahir, Massachusetts General Hospital, Boston, Massachusetts, United States

Glycated hemoglobin (A1c) is used to predict glycation burden and clinical outcomes in diabetic patients. However, the reliability of A1c in CKD has been questioned, with concerns including the competition between the two post-translational protein modifications, glycation and carbamylation, on the same protein amino groups. Whether carbamylation modifies the impact of A1c on outcomes in patients with diabetic CKD is unclear.


In 1,427 participants from the Chronic Renal Insufficiency Cohort (CRIC) study with co-existing CKD and diabetes, multivariable Cox regression models were applied to evaluate the association between A1c and CKD progression (ESRD or 50% eGFR decline) or first cardiovascular disease (CVD) event (congestive heart failure, myocardial infarction, or stroke), stratified by quartiles of carbamylated albumin (C-Alb) levels.


The mean age of participants was 60 years, mean eGFR was 38.1 mL/min/1.73 m2, mean A1c was 7.5%, and median C-Alb was 8.4 mmol/mol. During an average of 7.9 years of follow up, every 1% increase in A1c was associated with higher risks of CKD progression (HR 1.07, 95% CI 1.02, 1.12), and CVD (HR 1.09; 95% CI 1.04, 1.15) in adjusted models. However, in the highest C-Alb quartile, A1c was no longer associated with CKD progression or CVD; while in the lowest C-Alb quartile, A1c remained an independent risk factor for the adverse outcomes (Figure 1). Interaction testing between A1c and C-Alb was significant for CKD progression.


In patients with co-existing CKD and diabetes, the association between A1c and adverse clinical outcomes is modified by high carbamylation levels. This finding may explain why A1c is not as reliable in patients with CKD compared to the general diabetic population.

Figure 1. Association of hemoglobin A1c with outcomes in CRIC participants with CKD and diabetes, stratified by quartiles of C-Alb levels. Note hemoglobin A1c’s diminished HRs at higher C-Alb quartiles. The models are adjusted for age, sex, race/ethnicity, BMI, smoking status, CVD, HTN, ACEI/ARB, and LDL.


  • NIDDK Support