Carbamylation requires isocyanic acid derived from urea. Carbamylation of hemoglobin (Hb) produces carbamylated Hb (carbHb), which could serve as a marker of posttranslational protein modification possibly associated with such uremic complications as atherosclerosis. Since relative carbHb levels are determined by mean urea concentration and duration of exposure, they could be used to assess the adequacy of a patient’s hemodialysis (HD) regimen. We therefore determined the relationship between carbHb and urea kinetics in patients with chronic renal failure (CRF) undergoing maintenance HD. In pre-HD determinations as well as in nondialyzed subjects including healthy subjects and CRF patients without dialysis, carbHb correlated well with blood urea nitrogen (BUN) concentrations, especially with BUN averaged for the preceding 1–3 months. In HD patients, carbHb correlated significantly with urea kinetics (time-averaged concentration of urea, or TACurea, Kt/V and urea reduction rate). The estimated mean urea concentration in HD patients calculated from the relationship between carbHb and averaged BUN over 3 months in the nondialyzed groups was lower than TACurea, suggesting that TACurea may be an overestimate. Pre-HD BUN is not a good nutritional index since detrimental decreases in urea elimination from the body can elevate pre-HD BUN independently of nutrition. We therefore devised a new nutritional index, BUN/carbHb, which correlated significantly with serum albumin as well as the normalized protein catabolic rate. These results demonstrate that carbHb accurately reflects uremic control and the BUN/carbHb ratio could serve as an index of nutritional state in HD patients.

Lee JA, Lee HA, Sadler PJ: Uraemia: Is urea more important than we think? Lancet 1991;38:1438–1440.
Holtham SB, Schutz F: The effect of cyanate on the stability of proteins. Biochim Biophys Acta 1949;3:65–81.
Stark GR, Stein WH, Moore S: Reaction of the cyanate present in aqueous urea with amino acids and proteins. J Biol Chem 1960;235:3177–3181.
Fluckiger R, Harmon W, Meier W, Loo S, Gabbay KH: Hemoglobin carbamylation in uremia. N Engl J Med 1981;304:823–827.
Jensen M, Nathan DG, Bunn HF: The reaction of cyanate with the α and β subunits in hemoglobin. J Biol Chem 1973;248:8057–8063.
Horkko S, Savolainen MJ, Kervinen K, Kesaniemi YA: Carbamylation-induced alterations in low-density lipoprotein metabolism. Kidney Int 1992;41:1175–1181.
Kraus LM, Elberger AJ, Handorf CR, Pabst MJ, Kraus AP: Urea-derived cyanate forms ε-amino-carbamyl-lysine (homocitrulline) in leukocyte proteins in patients with end-stage renal disease on peritoneal dialysis. J Lab Clin Med 1994;123:882–891.
Prabhakar SS, Zeballos GA, Montoya-Zavala M, Leonard C: Urea inhibits inducible nitric oxide cell line. Am J Physiol 1997;273(6, pt 1):C1882–C1888.
Harding JJ: Post-translational modification of lens proteins in cataract. Lens Eye Tox Res 1991;8:245–250.
Kwan JTC, Carr EC, Bending MR, Barron JL: Determination of carbamylated hemoglobin by high-performance liquid chromatography. Clin Chem 1990;36:607–610.
Kwan JTC, Carr EC, Neal AD, Burdon J, Raftery MJ, Marsh FP, Barron JL, Bending MR: Carbamylated hemoglobin, urea kinetic modelling and adequacy of dialysis in haemodialysis patients. Nephrol Dial Transplant 1991;6:38–43.
Depner TA, Cheer A: Modeling urea kinetics with two vs three BUN measurements: A critical comparison. ASAIO Trans 1989;35:499–502.
Davenport A, Johns S, Goel S, Astley JP, Feest TG: Carbamylated hemoglobin: A potential marker for the adequacy of hemodialysis therapy in end-stage renal failure. Kidney Int 1996;50:1344–1351.
Stim J, Shaykh M, Anwar F, Ansari A, Arruda JAL, Dunea G: Factors determining hemoglobin carbamylation in renal failure. Kidney Int 1995;48:1605–1610.
Oimomi M, Ishikawa K, Kawasaki T, Kubota S, Yoshimura Y, Baba S: Carbamylation of hemoglobin in renal failure and clinical aspects. Metabolism 1984;33:999–1002.
Kwan JTC, Carr EC, Barron JL, Bending MR: Carbamylation haemoglobin in normal, diabetic and uraemic patients. Ann Clin Biochem 1992;29:206–209.
Davenport A, Jones SR, Goel S, Astley JP, Hartog M: Differentiation of acute from chronic renal impairment by detection of carbamylated haemoglobin. Lancet 1993;341:1614–1617.
Oimomi M, Matsumoto S, Hatanaka H, Ishikawa K, Kubota S, Yoshimura Y: Determination of carbamylated plasma protein and its clinical application to renal failure. Nephron 1985;40:405–406.
Han JS, Kim YS, Chin HJ, Joen US, Ahn C, Kim S, Lee JS, Jang IJ, Shin SG: Temporal changes and reversibility of carbamylated hemoglobin in renal failure. Am J Kidney Dis 1997;30:36–40.
Smith WGJ, Holden M, Benton M, Brown CB: Glycosylated and carbamylated haemoglobin in uremia. Nephrol Dial Transplant 1989;4:96–100.
Balion CM, Draisey TF, Thibert RJ: Carbamylated hemoglobin and carbamylated plasma protein in hemodialyzed patients. Kidney Int 1998;53:488–495.
Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A: Correlation of glucose regulation and hemoglobin A1c in diabetes mellitus. N Engl J Med 1976;295:417–420.
Kwan JTC, Carr EC, Barron JL, Bending MR: Carbamylated haemoglobin – A restrospective index of time-averaged urea concentration. Nephrol Dial Transplant 1993;8:565–567.
Bergstrom J, Lindholm B: Nutrition and adequacy of dialysis: How do hemodialysis and CAPD compare? Kidney Int 1993;43(suppl 40):S39–S50.
Tarif N, Shaykh M, Stim J, Arruda JA, Dunea G: Carbamylated hemoglobin in hemodialysis patients. Am J Kidney Dis 1997;30:361–365.
Lowrie EG, Lew NL: Death risk in hemodialysis patients: The predictive value of community measured variables and an evaluation of death differences between facilities. Am J Kidney Dis 1990;15:458–482.
Acchiardo SR, Moore LW, Latour PA: Malnutrition as the main factor in morbidity and mortality of hemodialysis patients. Kidney Int 1983;24(suppl 16):S199–S203.
Bergstrom J, Lindholm B: Malnutrition, cardiac disease, and mortality: An integrated point of view. Am J Kidney Dis 1998;32:834–841.
Canada-USA (CANUSA) Peritoneal Dialysis Group: Adequacy of dialysis and nutrition in continuous peritoneal dialysis: Association with clinical outcome. J Am Soc Nephrol 1996;7:198–207.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.