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The Impact of Carbamylation and Anemia on HbA1c’s Association with Renal Outcomes in Patients with Diabetes and Chronic Kidney Disease

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posted on 2022-11-18, 21:58 authored by Mengyao Tang, Anders Berg, Eugene P. Rhee, Andrew S. Allegretti, Sagar Nigwekar, Ananth Karumanchi, James P. Lash, Sahir Kalim

 

  

OBJECTIVE 

HbA1c can predict risk for microvascular complications in patients with diabetes. However, HbA1c’s reliability in chronic kidney disease (CKD) has been questioned, with concerns including competition from another post-translational protein modification, carbamylation, acting on the same amino groups as glycation; and anemia with reduced erythrocyte lifespans leading to altered glycation accumulation. We investigated whether carbamylation and anemia modify the impact of HbA1c on renal outcomes in patients with diabetes and CKD. 

RESEARCH DESIGN AND METHODS

In 1,516 participants from the Chronic Renal Insufficiency Cohort study with diabetes and CKD, Cox regression models were applied to evaluate the association between HbA1c and CKD progression (composite of end-stage kidney disease or 50% decline in estimated glomerular filtration rate [eGFR]), stratified by carbamylated albumin (C-Alb) quartiles and anemia. 

RESULTS

The mean eGFR was 38.1 mL/min/1.73 m2, mean HbA1c was 7.5% (58 mmol/mol), median C-Alb was 8.4 mmol/mol. HbA1c was lower in the higher C-Alb quartiles. During a median follow-up of 6.9 years, 763 participants experienced CKD progression. Overall, higher HbA1c was associated with an increased risk of CKD progression (adjusted hazard ratio 1.07, 95% CI 1.02-1.13). However, using stratified analyses, HbA1c was no longer associated with CKD progression in the highest C-Alb quartile, but did show a monotonic increase in CKD progression risk across each lower C-Alb quartile (P-interaction =0.022). Anemia also modified the association between HbA1c and CKD progression (P-interaction=0.025). 

CONCLUSIONS 

In patients with co-existing diabetes and CKD, the association between HbA1c and CKD progression is modified by carbamylation and anemia. 

  

Funding

U.S. Department of Health and Human Services > National Institutes of Health > National Heart, Lung, and Blood Institute R01HL133399

U.S. Department of Health and Human Services > National Institutes of Health > National Institute of Diabetes and Digestive and Kidney Diseases R01DK124453

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