Influence of in vivo hemoglobin carbamylation on HbA(1c) measurements by various methods

Increased carbamylated hemoglobin formed in erythrocytes during uremia may interfere with HbA(1c) assays, but few studies compared directly both param eters. We measured carbamylated hemoglobin by HPLC in 45 non-diabetic uremi c patients (16 with acute and two with chronic renal failure, 27 with trans plant recipients) as 57.8 +/- 22.3 mu g carbamylvaline /g Hb (mean +/- stan dard 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: Diam at (BioRad), 2: A1c2.2 (Tosoh) and 3: HA8140 (Menarini), and one immunoassa y method (Tinaquant II Roche). Whichever the method, mean HbA(1c) values ob tained increased in patients with high (> 60 mu g 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 ho wever 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 resul ts show that Hb adducts, whether due to carbamylation or to other chemical reactions, interfere to a variable extent with different HbA(1c) assay meth ods, and confirm that HbA(1c) values should be interpreted with caution in uremic patients.