Carbamylated Hemoglobin as a Therapeutic Marker in Hemodialysis

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 TAC_urea, K_t/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 TAC_urea, suggesting that TAC_urea 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.