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Quantifying rates of protein synthesis in humans by use of ²H₂O: application to patients with end-stage renal disease

¹Departments of Nutrition, ²Medicine, and ³Mathematics, Case Western Reserve University, Cleveland 44106; and ⁴Department of Nephrology, Cleveland Clinic Foundation, Cleveland, Ohio 44195

Submitted 17 June 2003 ; accepted in final form 4 December 2003

A method is introduced for quantitating protein synthetic rates in humans by use of ²H₂O. Its validity was tested in subjects with end-stage renal disease. Six clinically stable subjects, hemodialyzed three times weekly, ingested ²H₂O to a body water ²H enrichment of 0.4%. On dialysis, body water enrichment declined to 0.1%. Enrichment of the -hydrogen of plasma free alanine was also 0.4% before and 0.1% after dialysis. -Hydrogen enrichment was 80-100% of -hydrogen enrichment. ²H₂O was ingested to replace ²H₂O removed after each dialysis for 15-51 days, returning enrichment to 0.4%. Enrichment of alanine from plasma albumin gradually increased, with again 80-100% as much ²H in - as in -hydrogens. With continued dialyses, without ²H₂O replacement, alanine from albumin enrichment gradually declined, whereas free alanine and water enrichments were negligible. The fractional albumin synthesis rate, calculated from the increase in enrichment in alanine from albumin, was 4.0 ± 0.5%/day, and from the decrease, 4.6 ± 0.2%/day. Thus body water enrichment in a subject given ²H₂O can be maintained constant long term. A rapid exchange, essentially complete, occurs between the hydrogens of alanine and body water. An integrated measure over a long period of albumin's synthetic rate can be estimated from both the rise in enrichment of alanine from the protein during ²H₂O ingestion and fall on ²H₂O withdrawal, while the subject's living routine is uninterrupted. Estimates are in subjects with renal disease, but the method should be applicable to estimates of protein synthetic rates in normal subjects and in other pathological states.

protein; albumin; alanine; deuterium oxide; hemodialysis

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