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

Abstract

Increased carbamylated hemoglobin formed in erythrocytes during uremia may interfere with HbA1c 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 microg carbamylvaline/g Hb (mean +/- standard deviation) vs. 31.6 +/- 5.1 in 15 controls (+83%, p < 0.001). In these samples, HbA1c 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 HbA1c values obtained increased in patients with high (> 60 microg 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. HbA1c 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 HbA1c assay methods, and confirm that HbA1c values should be interpreted with caution in uremic patients.