OBJECTIVE

Glycated hemoglobin (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 posttranslational 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), and 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 coexisting diabetes and CKD, the association between HbA1c and CKD progression is modified by carbamylation and anemia.

ARTICLE HIGHLIGHTS

  • HbA1c’s reliability in chronic kidney disease (CKD) has been questioned, with concerns including competition between carbamylation and glycation and anemia affecting glycation accumulation.

  • We investigated whether carbamylation and anemia modify the impact of HbA1c on renal outcomes in patients with diabetes and CKD.

  • In 1,516 participants from the Chronic Renal Insufficiency Cohort (CRIC) study with diabetes and CKD, we found that the association between HbA1c and CKD progression was significantly diminished in patients with high carbamylation levels or presence of anemia.

  • This finding may explain why HbA1c is less reliable in patients with CKD compared with the general population with diabetes.

This article contains supplementary material online at https://doi.org/10.2337/figshare.21397479.

This content is only available via PDF.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/journals/pages/license.