Influence of in vivo Hemoglobin Carbamylation on HbA1c Measurements by Various Methods

Abstract

Increased carbamylated hemoglobin formed in erythrocytes during uremia may interfere with Hba_1c assays, but few studies compared directly both parameters. We measured carbamylated hemoglobin by HPLC in 45 non-diabetic uremic patients (16 with acute and two with chronic renal failure, 27 with transplant recipients) as 57.8 ± 22.3 μg carbamylvaline/g Hb (mean ± standard deviation) vs. 31.6 ± 5.1 in 15 controls (+83%, p < 0.001). In these samples, HbA_1c was evaluated by three ion-exchange HPLC methods, 1: Diamat (BioRad), 2: A1c2.2 (Tosoh) and 3: HA8140 (Menarini), and one immunoassay method (Tinaquant II Roche). Whichever the method, mean HbA_1c values obtained increased in patients with high (> 60 μg carbamylvaline/g Hb) vs. low (< 45) carbamylated hemoglobin values (+0.08 to 0.25% of total Hb), but differences were not significant. Minor peaks on the chromatograms were however increased in parallel to carbamylated hemoglobin. HbA_1c values over 6% were found in 4, 1, 2 and 0 samples, with HPLC 1, 2, 3 and immunoassay, respectively. Fructosamine values were not significantly altered. Our results show that Hb adducts, whether due to carbamylation or to other chemical reactions, interfere to a variable extent with different HbA_1c assay methods, and confirm that HbA_1c values should be interpreted with caution in uremic patients.